bluuebunny/crossref_metadata_2025 huggingface dataset:
Esophageal Cancer—An Update Review
Authors: Liu Yang , Gibson Michael K ,   Fellow, Division of Hematology/Oncology,   Assistant Professor of Medicine/Oncology and Cardiothoracic Surgery Co-Leader, Esophageal Cancer Program, University of Pittsburgh Medical Center, PA, US.
Published: October 2015

With the decrease of cancer incidences in a few major cancers, such as breast cancer and lung cancer, the incidence of esophageal cancer has still been climbing up steadily for the past decades, especially adenocarcinoma. Our views on esophageal cancer have been evolving as well. Modifications of the American Joint Committee on Cancer (AJCC) staging has been implemented in its recent edition in 2010. Diagnostic and follow-up standards are changing with more and more physicians and hospitals considering endoscopic ultrasound-guided biopsy as a minimal requirement for definitive diagnosis and accurate staging. In some large centers and by some physicians, laproscopic/ thorascopic biopsy are attempted to diagnose esophageal cancer with more accurate definitive staging. The widespread use of imaging studies, such as computed tomography and/or positon emission tomography, has improved the diagnosis in guiding the therapeutic options. In early stage esophageal cancer management, the acceptable modalities are still radiofrequency ablation, endoscopic mucosal resection, and photodynamic therapy. The advantages and disadvantages are discussed in this article. Surgical resection of early esophageal cancer of T2 or greater staging or N1 is still considered standard with potential to ‘cure’ while minimal invasive laproscopic surgery showed acceptable improved effects and quality of life but are still limited to some tertiary centers. Multi-modality therapies of esophageal cancer in locally advanced stage, both resectable and unresectable, are discussed in this review. For operable diseases, neoadjuvant therapy, peri-surgery therapy, adjuvant therapy, chemotherapy, and/or radiation therapy are discussed. Unresectable esophageal cancer of both adenocarcinoma and squamous cell carcinoma as well as cancer with Her2/neu expression are also considered. The attached table listed the major landmark phase III clinical trials involving esophageal carcinoma. Metastatic cancer management, including the importance of quality of life management among the survivors is also examined.
Technologic Advances in External Beam Radiotherapy for Head and Neck Cancer
Authors: Gestel Dirk Van , Gregoire Vincent , Vermorken Jan B ,   Radiation Oncologist, University Radiotherapy Department Antwerp, Belgium,   Professor in Radiation Oncology, Radiation Oncology Department and Centre for Molecular Imaging and Experimental Radiotherapy, St-Luc University Hospital, Brussels, Belgium,   Emeritus Professor of Oncology, Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium
Published: October 2015

Purpose:Radiotherapy (RT) has evolved substantially since its first clinical use in 1896. Most recently, the introduction of the computed tomography (CT) scan in the 1980s launched 2 decades of technologic (r)evolution. In this article we will give an overview of the recent technical advances in external beam RT for head and neck cancer (HNC).Discussion:In HNC, intensity-modulated RT (IMRT) has become standard of care as it has shown superiority over 3D conformal RT in terms of prevention of xerostomia. Other treatment options are fractionated stereotactic RT as a boost and the use of particle therapy with its interesting ballistic capacities. Carbon ions will be mainly used for radio-resistant cancers because of the supplementary higher biologic effect. Adaptive RT is promising but needs much more evolution before it can be optimally used. All these new techniques require a high level of image guidance in order to reach their maximal capacities. Rigorous quality assurance of all the different steps in the irradiation process is essential to deliver the right dose exactly at the right place.Conclusion:The recent rapid technologic evolution in RT is particularly interesting for HNC as it permits better sparing of the many radiosensitive organs in close vicinity to these aggressive tumors.
Castration-resistant Prostate Cancer— Chemotherapies and Molecular Targets
Authors: Bahl Amit ,   Consultant Oncologist and Clinical Director, Bristol Haematology and Oncology Centre, University Hospitals, Bristol, UK
Published: October 2015

Castration-resistant prostate cancer (CRPC) has a poor prognosis: current chemotherapeutic approaches ultimately result in resistance and are associated with survival rates of less than 2 years. However, the last decade has seen an expansion in the number of therapeutic options for CRPC and the regulatory approval of several agents, including the chemotherapy drug cabazitaxel and the targeted agents abiraterone acetate, enzalatumide, and denosumab. Novel targeted agents inhibit androgen receptor-mediated signaling, and nonhormonal targets, including apoptosis, signal transduction pathway inhibitors, angiogenesis, and bone and immune microenvironments. Clinical trials of these agents, however, have demonstrated varied efficacy. Among the drugs in clinical development, custirsen, cabozantinib, and dasatinib are among the most promising. There is a requirement for studies directly comparing agents, and for improved patient selection to identify patients benefitting from a particular therapy.
Management of Isolated Nodal Recurrence After Head and Neck Cancer Treatment
Authors: Ling-yu Chow Velda , Yu-Wai Chan Jimmy ,   Resident,   Division Chief and Assistant Professor, Division of Head and Neck Surgery, Department of Surgery, University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, Hong Kong SAR
Published: October 2015

The status of the regional cervical lymphatics is one of the most significant prognostic indicators in head and neck cancers. The traditional treatment for cancers with cervical nodal metastasis has been surgical. With the global trend toward organ-preserving therapy, chemoradiation has gained increasing popularity over primary surgical therapies for cancers in the head and neck region. The subsequent management of the neck for those with residual or recurrent nodal metastasis, however, has become one of the most debated topics in the field of head and neck oncology. This review addresses several important controversies, including the optimal assessment of the nodal response to chemoradiation, the potential role and the oncological results of planned and salvage neck dissection after chemoradiation, and the type and extent of neck dissection required in order to achieve the optimal balance between tumor control and surgical morbidities. Further clinical trials and ongoing researches will help us to define the best therapeutic option in such circumstances.
Could Metabolic Therapy Become a Viable Alternative to the Standard of Care for Managing Glioblastoma?
Authors: Seyfried Thomas N , Marsh Jeremy , Mukherjee Purna , Zuccoli Giulio , D’Agostino Dominic P ,   Professor of Biology,   Bachelor of Science,   Research Assistant Professor, Biology Department, Boston College, Chestnut Hill, Massachusetts, US,   Section Chief, Section of Neuroradiology, Children’s Hospital of Pittsburgh, and Associate Professor of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, US,   Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, US
Published: October 2015

Little progress has been made in the long-term management of glioblastoma multiforme (GBM) for more than 40 years. The current standard of care (SOC) for GBM involves radiotherapy with concomitant adjuvant temozolomide chemotherapy. Perioperative corticosteroids are also administered to the majority of GBM patients. The current standard treatment strategy for GBM increases availability of glucose (from steroids) and glutamine (from radio-necrosis) in the tumor microenvironment. Emerging evidence indicates that GBM, like most cancers, is a metabolic disease displaying a robust Warburg effect. It is well documented that glucose and glutamine are major metabolic fuels that drive tumor progression. Recent evidence suggests that neoplastic cells with macrophage/microglia properties can contribute to the most invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells as well as for the more rapidly proliferating cancer cells. Metabolic therapy exploits the biological differences between tumor cells and normal cells for the non-toxic targeting of the tumor cells. Studies in preclinical models show that calorie restricted ketogenic diets (KD-R), anti-glycolytic drugs, and hyperbaric oxygen therapy can reduce availability of glucose and glutamine in the tumor microenvironment while enhancing oxidative stress in tumor cells. The predominant ketone body (β-hydroxybutyrate) reduces oxidative stress in normal brain cells. The potential success of metabolic therapy was also seen in human glioma case studies suggesting that this therapeutic strategy could become a viable alternative to the SOC.
Sequencing of Therapy in Breast Cancer
Authors: McVeigh Terri P , Kerin Michael J ,   Postgraduate Surgical Researcher, Discipline of Surgery, Clinical Sciences Institute, National University of Ireland, Galway, Ireland,   Professor of Surgery, National University of Ireland, Galway, Ireland
Published: October 2015

Breast cancer represents a common malignancy in the developed world. The treatment of breast cancer is multimodal, and includes surgical management, chemotherapy, radiation, and hormonal modulation. The selection and sequencing of the different facets of treatment are based on patient and tumor variables, including prognostic scores and desire for breast conservation or reconstruction. The role of irradiation of the breast in breast-conserving surgery is well established. Radiation of the chest wall post mastectomy has also been associated with survival benefit in patients with node-positive disease. Unlike several cancers for which preoperative chemoradiation is the standard of care, radiation is generally reserved as a final step in the treatment of breast cancer, and can delay reconstruction, as the presence of an autologous flap or an implant may reduce the capacity to deliver effective chest wall radiation. The question arises therefore, if neoadjuvant radiotherapy delivered after tumor chemosensitization, but in advance of definitive surgery, might offer an advantage over adjuvant radiotherapy.
Radiation Therapy in Male Breast Cancer
Authors: Bagshaw Hilary P , Cloyd Jordan M , Poppe Matthew M , Wapnir Irene L ,   Resident Physician, Department of Radiation Oncology, University of Utah, Salt Lake City, Utah, US,   Resident Physician, Department of Surgery, Stanford University, California, US,   Assistant Professor, Department of Radiation Oncology, University of Utah, Salt Lake City, Utah, US,   Professor, Department of Surgery, Stanford University, California, US
Published: October 2015

Male breast cancer (MBC) is a relatively rare disease and because the dedicated literature on MBC is limited, management typically follows guidelines established for female breast cancer (FBC). Although radiation therapy (RT) constitutes a critical role in the treatment of MBC, several unique challenges influence its use. Most men with breast cancer present at an older age with more extensive and advanced stage disease than women. In contrast to the predominance of breast conservation therapy in women with breast cancer, the majority of men are treated with mastectomy, with or without post-mastectomy radiation. Although no prospective or randomized trials are available, retrospective data suggests that surgery followed by adjuvant RT significantly improves locoregional control (LRC) in men. This article reviews the utilisation, efficacy, and complications associated with adjuvant RT in MBC.
Low-dose Interleukin-2 in the Treatment of Autoimmune Disease
Authors: Koreth John , Ritz Jerome , Tsokos George C , Pugliese Alberto , Malek Thomas R , Rosenzwajg Michelle , Klatzmann David ,   Assistant Professor,   Attending Physician,   Professor, Dana-Farber Cancer Institute, Boston, Massachusetts, US,   Professor of Medicine, Harvard Medical School, Boston, Massachusetts, US,   Chief, Division of Rheumatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, US,   Professor of Medicine, Harvard Medical School, Boston, Massachusetts, US,   Professor of Medicine, Immunology, and Microbiology, Division of Diabetes, Endocrinology and Metabolism, and Head, Immunogenetics Program, Division of Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, US,   Professor and Vice-Chair, Department of Microbiology and Immunology, and Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, US,   Associate Professor of Immunology and Head of the Clinical Immunology Laboratory, Biotherapy Department, Sorbonne University, Pierre and Marie Curie Medical School, Pitié-Salpêtrière Hospital, Paris, France,   Professor of Immunology and Head of Department, Inflammation-Immunopathology-Biotherapy Department, Sorbonne University, Pierre and Marie Curie Medical School, Pitié-Salpêtrière Hospital, Paris, France,   Head, U959 INSERM Research Unit, Paris, France
Published: October 2015

CD4+ regulatory T cells (Tregs) act to maintain peripheral immune tolerance. Decreased numbers or defective function of Tregs has been implicated in the pathogenesis of various autoimmune diseases. Interleukin-2 (IL-2) at high doses is approved by the US Food and Drug Administration (FDA) as an immune stimulant to induce anti-tumor cytotoxicity. However, at physiologic doses, IL-2 is necessary for the expansion and function of Tregs. Treatment with low-dose IL-2 can selectively enhance Treg function while avoiding the activation of effector T cells and ameliorate immune inflammation. Administration of low doses of IL-2 to patients suffering from chronic graft versus host disease (cGvHD) or chronic hepatitis C-mediated vasculitis resulted in significant clinical benefit, which was linked to improved Treg cell function. Preclinical studies suggest that low-dose IL-2 may offer benefit in other autoimmune diseases including systemic lupus erythematosus and type 1 diabetes. Ongoing preclinical and clinical studies indicate a wider potential role for low-dose IL-2 based Treg therapeutics in human autoimmune diseases.
Translating Promising Biomarkers into Oncology Clinical Practice
Authors: Lively Tracy G , Sachs Michael C , Conley Barbara A ,   Deputy Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Department of Health and Human Services,   Mathematical Statistician, Biometric Research Branch Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Department of Health and Human Services,   Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Betheseda, US
Published: October 2015

There is a clear need for biomarker assays that can assist in the choice of the best treatment for individual cancer patients. Many manuscripts can be found in the literature that describe promising correlations of molecular features with cancer outcomes, but few of these ever translate to assays that come into common clinical use. Some reasons for this lack of development are the failure to define a clear and compelling intended use for the biomarker assay, as well as the paucity of necessary and careful validation studies: the analytical and clinical validation of a given assay, optimization for clinical use, and demonstration of the clinical utility of the assay. These steps often require resources beyond those of the original laboratory that defined the correlation of the biomarker result to clinical outcome. This manuscript details some of the matters that are faced by assay developers, as well as some solutions for improved assay development and validation.
How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?
Authors: Mateos María-Victoria ,   Consultant Physician, Hospital Universitario de Salamanca-Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
Published: October 2015

Multiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring quality of life. Melphalan plus prednisone has been the classic backbone to which proteasome inhibitors and immunomodulatory drugs were added and, recently, lenalidomide plus low-dose dexamethasone emerged as a new standard of care, free of alkylator, and also as a backbone to which secondgeneration proteasome inhibitors are being added. Monoclonal antibodies will take part of these treatments regimens in the future. Prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. Finally, elderly patients under treatment require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining their quality of life.
How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?
Authors: Mateos María-Victoria ,   Consultant Physician, Hospital Universitario de Salamanca-Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
Published: October 2015

Multiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring quality of life. Melphalan plus prednisone has been the classic backbone to which proteasome inhibitors and immunomodulatory drugs were added and, recently, lenalidomide plus low-dose dexamethasone emerged as a new standard of care, free of alkylator, and also as a backbone to which second-generation proteasome inhibitors are being added. Monoclonal antibodies will take part of these treatments regimens in the future. Prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. Finally, elderly patients under treatment require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining their quality of life.
Chemotherapy-induced Neuropathy—Where Are We Now?
Authors: Ruddy Kathryn J , Majithia Neil , Pachman Deirdre R , Beutler Andreas S , Loprinzi Charles L ,   Assistant Professor of Oncology,   Internal Medicine Resident,   Assistant Professor of Medicine and Oncology,   Assistant Professor of Oncology,   Professor of Oncology, Mayo Clinic, Rochester, Minnesota, US
Published: October 2015

Among the most debilitating of chemotherapy-related toxicities is neuropathy, which is associated with several commonly used oncologic agents. The specific characteristics of neurotoxicity vary between inciting drugs, with important differences in symptom characteristics and clinical course. No medications have been found to effectively prevent chemotherapy-induced neuropathy, and investigations of predictors of severe neurotoxicity to date explain only a small part of susceptibility (making it difficult to tailor chemotherapies to individual risk). Treatment has also been challenging. Although duloxetine is modestly beneficial, and Scrambler therapy shows promise in preliminary studies, no other therapies have been proved to be effective.
Current and Emerging Therapies in Metastatic Prostate Cancer
Authors: Vankayala Hema , Vaishampayan Ulka ,   Medical Oncologist, John D Dingell VA Medical Center,   Professor of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, US
Published: October 2015

The face of metastatic prostate cancer (PC) has been remarkably reshaped with the current advances in its management. Kudos to the cuttingedge research that has pinpointed new targets and agents. The main stumbling block in this disease is progression on androgen deprivation therapy (ADT) and the development of castrate resistance. Despite this phenomenon, the majority of patients with PC continue to rely on androgen receptors (ARs) for disease growth and progression. Several of these newer agents directly or indirectly target ARs. Many drugs have earned US Food and Drug Administration (FDA) approval in the past decade by showing survival benefit, which is the gold standard endpoint in all the pivotal PC trials. An array of new targets and agents are being explored currently. The future of metastatic castration-resistant prostate cancer (mCRPC) appears exciting with the expanding armamentarium; however, the challenges of affordability and sequencing of the agents remain.
Two Decades of Progress in the Management of a Rare Disease—Peritoneal Mesothelioma
Authors: ugarbaker Paul H ,   Medical Director, Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, US
Published: October 2015

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare but aggressive disease with a poor sustained response to systemic chemotherapy. Historically, the median survival has been less than 1 year. The disease rarely disseminates outside of the peritoneal space suggesting that local-regional treatment options may be effective in the long-term control of this malignancy. Establishment of a referral center to concentrate experience with the management of this disease has contributed greatly to progress in its management.Materials and methods:Through a series of Institutional Review Board-approved protocols, a long-standing morbidity/mortality assessment, numerous manuscripts published in the peer-reviewed literature, and participation in numerous national and international workshops, a new standard of care with expectations of long-term survival in a majority of patients has evolved.Results:The surgery for this disease has evolved through a sequence of peritonectomy procedures and visceral resections whose goal is to remove all visible evidence of disease. The first step in successful treatment is a complete cytoreduction. After the cancer resection in the operating room, hyperthermic perioperative chemotherapy (HIPEC) is used. A three-drug protocol combines heat-augmented chemotherapy within the peritoneal space and systemic chemotherapy that is heat-augmented as a continuous infusion intravenously. Catheters are placed for early postoperative intraperitoneal chemotherapy using paclitaxel for 5 days. Also placed at the time of the cytoreductive surgery is an intraperitoneal port for long-term combined intraperitoneal and systemic chemotherapy using cisplatin and pemetrexed for 6 months. Patients having the long-term bidirectional chemotherapy have shown statistically significant improved survival compared with those patients who had surgery alone plus the perioperative chemotherapy. There have been no mortality and the grade 4 adverse events have been prospectively accumulated as 12 %.Conclusions:With continued effort, the surgery and long-term regional chemotherapy for DMPM has continued to improve over 20 years. Currently, a management plan that involves cytoreductive surgery, perioperative chemotherapy, and long-term bidirectional chemotherapy has changed the natural history of this disease. A global registry has been initiated to confirm the benefits of these extended treatments.
Thyroid Nodules - Management Dilemmas and Theraputic Considerations
Authors: Castro M Regina
Published: October 2015

Thyroid nodules are very common in clinical practice, with an overall prevalence that varies from 4% by palpation to 67% by ultrasonography. The annual incidence by palpation has been estimated at 0.09% by the Framingham study,1which translates into approximately 300,000 new nodules in the US in 2005. Despite their high frequency, only a small fraction (~5%) of thyroid nodules harbor cancer. Because only malignant or large, symptomatic nodules will require surgical excision, a systematic approach to their evaluation is important to avoid unnecessary surgery. Certain aspects in the evaluation and management of thyroid nodules remain controversial or represent clinical dilemmas.
Potential Therapeutic Role of Androgens in Cognitive Loss Associated with Hypogonadism
Authors: Tan Robert S , Ojeih Chris , Carrejo Maurita
Published: October 2015

Memory problems late in life are common and are often easy to recognize. Hypogonadism in older men is not as readily identified, but it is also frequently a part of aging. Androgens, such as testosterone, have important hormonal influences on the brain and may prevent and possibly treat cognitive loss, including age-associated memory loss, mild cognitive impairment (MCI), and perhaps even Alzheimer’s disease (AD).There is support from small, prospective clinical trials that suggest the role of testosterone in improving cognitive function in normal men as well as hypogonadal men with AD. This improvement in cognitive function is subtle and is often only measurable on specialized neuropsychological batteries such as those that measure the visual-spatial domain. Patients often report measurable memory improvement in both declarative and procedural domains after receiving testosterone replacement therapy.The rise of gonadotropins, follicle-stimulating hormones (FSHs), and luteinizing hormones (LHs), has been associated with AD.The clinical significance of therapeutic strategies directed to reduce these levels remains to be determined. Current evidence showing that dehydroepiandrosterone (DHEA) improves cognitive function is ambiguous.
Sexual Medicine - 2005 Update on Key Treatment Issues for Men with Erectile Dysfunction and their Partners
Authors: Goldstein Irwin
Published: October 2015

Sexual medicine is a rapidly evolving discipline that embraces the study, diagnosis, and treatment of sexual health concerns in men and women.1Data from multiple population-based epidemiologic studies estimate that approximately half of men and women will experience some sexual problems.2,3Based on data and well recognized psychologic and biologic burdens associated with sexual health, the role of sexual medicine will inevitably expand in medical healthcare management, research, and education.2,3Multidisciplinary organizations dedicated to advancing the practice of sexual medicine, include the American Urological Association (AUA), the International Society for Sexual Medicine (ISSM), and the International Society for the Study of Women’s Sexual Health (ISSWSH).
Advances in the Treatment of Erectile Dysfunction
Authors: Burnett Arthur L
Published: October 2015

Progress in the clinical management of erectile disorders, and specifically erectile dysfunction (ED), has gained substantially from basic science advances in the field. Unquestionably, the advance of phosphodiesterase 5 (PDE5) inhibitor therapy quickly followed the basic scientific description of nitric oxide (NO) signaling in erectile tissue. Further investigation of the neurotransmission involved in penile erection, hormone actions involved in this response, and biochemical signal transduction processes within the erectile tissue represent major areas of scientific pursuit. Current objectives scientifically are to identify and characterize molecular targets operating at multiple levels of the nervous system, endocrine system, and vascular system all related to penile erection. It is conceivable that new knowledge involving these systems may be exploited to develop various therapeutic approaches to manage ED. These approaches include pharmacotherapy, growth factor interventions, cell and tissue engineering, and gene therapy.
Investigating Inhaled Insulin
Authors: Zamudio Virginia
Published: October 2015

A Novel Delivery System

Inhaled human insulin (Exubera®) is the newest innovation in insulin therapy. The idea of delivering insulin via the pulmonary system, however, is not entirely new. In 1925, the German scientist Dr M Gänsslen published an article proposing the idea of inhaled insulin.1 Unfortunately, the science to accomplish this feat has eluded us until now. The limiting factors have been two-fold: developing a dry, powdered insulin of the right particle size; and manufacturing a mechanical device that will adequately deliver it into the deep lung.
Anti-diabetic Treatment in Obese Patients with Type 2 Diabetes Effects of Medication on Body Weight
Authors: Krentz Andrew J
Published: October 2015

Obesity is a major risk factor for the development of type 2 diabetes;1–3moreover, the presence of obesity in type 2 diabetes is associated with an increased risk of vascular complications associated with the disorder.4,5The majority of patients are overweight or obese at diagnosis of type2diabetes. Recent clinical trials have demonstrated that progression to diabetes in obese patients with impaired glucose tolerance can be prevented through weight reduction and increased levels of physical activity.6,7For patients who have developed type 2 diabetes, intentional weight loss has many potential benefits including improved metabolic control and a reduced need for antidiabetic medications.8–10
Hypothyroidism Talking Points 2006
Authors: Garber Jeffrey R
Published: October 2015

In 1603 Paracelsus described endemic cretinism. Over 150 years later, in 1878, Ord proposed the term myxedema to describe the clinical features of the “‘cretinoid’ affection occasionally observed in middleaged women”. In 1883, Emil Theodor Kocher reported myxedema after thyroidectomy. This led to a 1909 Nobel Prize in Medicine “for his work on the physiology, pathology and surgery of the thyroid gland.” Modern endocrinology’s birth followed in 1891 when Murray injected sheep thyroid extract into a patient with myxedema. Just one year later injection was replaced by “eating ground or fried sheep thyroid or tablets of dried thyroid tissue.”
Doing More with What We Already Know—Prevention and Improved Coverage of Healthcare for Diabetes
Authors: Whiting David ,   Epidemiologist and Public Health Specialist, International Diabetes Federation (IDF)
Published: October 2015

Diabetes now affects 285 million people, representing 6.6% of the world’s adult population. It disproportionately affects the developing world, with four of five people with diabetes living in low- and middle-income countries (LMCs). Diabetes is expected to cost the world at least $376 billion (11.6% of total healthcare expenditure) in 2010, according to theIDF Diabetes Atlas. This means that LMCs will also bear the economic brunt of the disease, which affects far more people of working age than previously believed. In many of these countries, essentials for good basic care for diabetes are scarce. The International Diabetes Federation (IDF) believes that where care for diabetes is scarce or limited, improving the coverage of prevention measures and basic care for diabetes will improve outcomes and quality of life. Good basic care can be highly cost-effective or even cost-saving. Even if costs are higher, the number of people affected by diabetes is now so large that it is no longer acceptable to ignore it.
‘Too Much Sitting’ and Metabolic Risk—Has Modern Technology Caught Up with Us?
Authors: Dunstan David W , Healy Genevieve N , Sugiyama Takemi , Owen Neville ,   Baker IDI Heart and Diabetes Institute, Melbourne,   Department of Epidemiology and Preventive Medicine, Monash University, Melbourne,   Cancer Prevention Research Centre, School of Population Health, The University of Queensland,   School of Exercise and Nutrition Sciences, Deakin University, Melbourne,   Vario Health Institute, Edith Cowan University, Perth,   Baker IDI Heart and Diabetes Institute, Melbourne,   Cancer Prevention Research Centre, School of Population Health, The University of Queensland,   Cancer Prevention Research Centre, School of Population Health, The University of Queensland,   Cancer Prevention Research Centre, School of Population Health, The University of Queensland
Published: October 2015

Recent epidemiological evidence suggests that prolonged sitting (sedentary behavior: time spent in behaviors that have very low energy expenditure, such as television viewing and desk-bound work) has deleterious cardiovascular and metabolic correlates, which are present even among adults who meet physical activity and health guidelines. Further advances in communication technology and other labor-saving innovations make it likely that the ubiquitous opportunities for sedentary behavior that currently exist will become even more prevalent in the future. We present evidence that sedentary behavior (too much sitting) is an important stand-alone component of the physical activity and health equation, particularly in relation to cardio-metabolic risk, and discuss whether it is now time to consider public health and clinical guidelines on reducing prolonged sitting time that are in addition to those promoting regular participation in physical activity.
Progression from Basal to Pre-mixed or Rapid-acting Insulin—Options for Intensification and the Use of Pumps
Authors: Sharma Morali D , Garber Alan J ,   Associate Professor of Medicine,   Professor of Medicine, Biochemistry, and Molecular Biology, and Molecular and Cellular Biology, Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine
Published: October 2015

Initiating insulin therapy is an important step in the management of patients with type 2 diabetes. The insulin regimen prescribed should be physiological and designed to control fasting and post-prandial glucose levels. The primary goals of therapy are achieving and maintaining tight glycemic control. The optimal insulin regimen should be patient-specific, taking the patient’s lifestyle into consideration. As their diabetes progresses, an increasing number of patients require insulin therapy. An initial approach is to add basal insulin to oral hypoglycemic agents. When this regimen fails to achieve glycemic control, it should be intensified by either adding a rapid-acting insulin analog to control postprandial hyperglycemia or switching to pre-mixed insulin injection initiated once daily and subsequently up to three times daily. More tools are now available, including injection devices, insulin pens, glucose monitoring devices, and insulin pumps, to overcome the barriers to initiating and intensifying insulin therapy. With new insulin analogs it is possible to intensify insulin therapy to achieve glycemic control targets without increasing the risk for hypoglycemia or causing excessive weight gain.
How Should Diabetes Be Treated to Minimize the Risk of Cardiovascular Complications?
Authors: Genuth Saul M ,   Professor of Medicine, Division of Molecular and Clinical Endocrinology, School of Medicine, Case Western Reserve University
Published: October 2015

Recognizing the great need to finally resolve the issue of whether lowering blood pressure with intensive treatment will decrease cardiovascular disease (CVD) events in type 2 diabetes, three randomized clinical trials were recently completed. ACCORD, VADT, and ADVANCE all found no significant benefit on primary CVD outcomes and ACCORD reported a 20% increase in total and CVD mortality with intensive treatment. A post-trial observational study by the UKPDS finally noted a decrease of 15% in myocardial infarction and 13% decrease in total mortality over a follow-up of 25 years from the diagnosis of diabetes. The BARI 2D trial found no significant overall advantage of insulin-sensitizing over insulin-providing drugs in these outcomes, although insulin-sensitizing augmented the benefit of coronary bypass surgery over medical therapy. Lowering blood pressure, low-density lipoprotein cholesterol, triglycerides, excessive body fat, and tobacco intake and raising high-density lipoprotein cholesterol may simply overwhelm the small additional benefit gained from reducing glycemia. Metformin has the largest body of evidence supporting its use for decreasing CVD events while reducing glycemia, but uncertainty still surrounds thiazolidinediones.
The Role of Advanced Glycation End-products in the Etiology of Insulin Resistance and Diabetes
Authors: Vlassara Helen , Striker Gary E ,   Professor of Diabetes and Aging, and Professor of Medicine, Molecular Medicine, and Geriatrics, and Director, Division of Experimental Diabetes and Aging,   Professor of Medicine, Department of Medicine and Department of Geriatrics, Mount Sinai School of Medicine
Published: October 2015

Despite new and effective drug therapies, insulin resistance (IR) and type 2 diabetes and its complications remain major medical challenges. It is known that IR, often associated with overnutrition and obesity, results from elevated oxidant stress (OS) and chronic inflammation. Less widely known is that a major cause for this inflammation is excessive consumption of advanced glycation end-products (AGEs) by the citizens of developed countries. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk factor for islet β-cell injury, peripheral IR, and diabetes. This article will discuss the relationships between exogenous AGEs, chronic inflammation, IR, and type 2 diabetes. We present new insights on the failure of innate immune defense mechanisms under chronic oxidant overload, which increase susceptibility to IR and type 2 diabetes and its complications. Finally, we describe evidence on AGE restriction, a new non-pharmacologic intervention, which effectively reduces persistent IR, restores innate immune functions, and, thus, optimizes current antidiabetic drug therapies.
Diabetes and the Brain—An Overview of Existing Knowledge and Discussions and Future Implications
Authors: Moheet Amir A , Seaquist Elizabeth R ,   Endocrinology Fellow,   Professor and the Pennock Family Chair in Diabetes Research, Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota
Published: October 2015

Diabetes affects many organ systems including the brain. Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function, including memory, psychomotor efficiency and executive function. In addition, structural abnormalities in the brain have been noted in subjects with both type 1 and type 2 diabetes using a variety of imaging techniques. The underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood but hyperglycemia, insulin resistance and vascular disease are likely to have key roles. Future research is needed to better understand of the natural history of the cerebral complications of diabetes and to identify the underlying mechanisms that lead to changes in brain function and structure.
Blood Glucose Monitoring In Pediatric Patients—Looking Toward Better Diabetes Management and Perspectives for the Future
Authors: Clarke William L ,   Robert M Blizzard Professor of Pediatric Endocrinology and Chief of Pediatric Endocrinology, Department of Pediatrics, University of Virginia Health Sciences Center
Published: October 2015

Self-blood glucose monitoring (SBGM) is an important component of day-to-day diabetes management for children and their families. Despite some recent concerns in terms of its analytical accuracy, it has been used successfully to implement intensive glucose control in the Diabetes Control and Complications Trial, reduce glycated hemoglobin (HbA1c) levels, prevent acute complications, and make it possible for children to attend school and participate in sports activities safely. While still in its infancy, continuous glucose monitoring (CGM) has been shown to be useful in reducing the occurrence of nocturnal hypoglycemia, lowering HbA1clevels, and reducing glycemic variability. Its analytical accuracy has prevented its approval as an alternative to SBGM for insulin decision-making. However, it has made possible the development and testing of closed-loop ‘artificial pancreas’ systems for controlling glucose levels in adults and adolescents.
Progress with Closed-loop Systems in Type 1 Diabetes
Authors: Leelarathna Lalantha , Hovorka Roman ,   Clinical Research Associate,   Principal Research Associate, Institute of Metabolic Science, University of Cambridge
Published: October 2015

Automated insulin delivery by means of a glucose-responsive closed-loop system has often been cited as the ‘holy grail’ of type 1 diabetes management. Reflecting the technological advances in interstitial glucose measurements and wider use of continuous glucose monitoring, recent research in closed-loop glucose control has focused on the subcutaneous route for glucose measurements and insulin delivery. The primary aim of such systems is to keep blood glucose within the target range while minimizing the risk of hypoglycemia with minimal input from the user. This article examines recent developments in the field of interstitial glucose measurement, limitations of the current generation of devices and implications on the performance of closed-loop systems. Clinical results and the advantages and disadvantages of different closed-loop configurations are summarized. Potential future advances in closed-loop systems are highlighted.
Specialty Drugs for the Treatment of Short Stature in Children—Pros, Cons, and Perspectives for the Future
Authors: Koontz Michaela B , Cuttler Leona ,   Assistant Professor, Department of Pediatrics, Division of Pediatric Endocrinology, Diabetes, and Metabolism,   William T Dahms Professor of Pediatrics, Chief of Pediatric Endocrinology, Diabetes, and Metabolism, and Director of The Center for Child Health and Policy, Rainbow Babies and Children’s Hospital, Case Western Reserve University
Published: October 2015

Specialty drugs are generally defined as medications that involve special drug handling and/or parenteral administration and are typically used to treat complex medical conditions. They are typically biologicals, often very expensive, and generally prescribed by specialists. The recent surge in use of specialty pharmaceuticals has placed these drugs in the spotlight as policy-makers struggle to contain healthcare costs. Specialty drugs are central to discussions about optimal ways to manage childhood short stature; recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-1 (rhIGF-1)—specialty drugs with annual prices of $20,000 to $30,000 per child—are available to treat childhood short stature from specific causes. rhGH and rhIGF-1 revolutionized treatment of severe short stature resulting from growth hormone deficiency and growth hormone insensitivity, respectively. Over the past 20 years, use of rhGH has expanded to other conditions. Expanded use of the newer rhIGF-1 may occur in an analogous manner. This article reviews the background, current status, and potential for these drugs in view of current evidence and policies.
Thiazolidinediones in Diabetes Management—An Overview of the Controversies, Current Status, and Perspectives for the Future
Authors: McCall Anthony L ,   James M Moss Professor of Diabetes, University of Virginia Health System
Published: October 2015

Patients with diabetes have a high risk for cardiovascular disease (CVD) and CVD is the most common cause of death and the largest source of societal expenditure related to diabetes. The worldwide prevalence of diabetes is skyrocketing with estimates projecting more than 350 million new cases within the next 20 years, portending a large increase in CVD in those with both diabetes and the even larger group of people with pre-diabetes. There are numerous drug therapies used for treatment and prevention of diabetes. Three years ago, a blockbuster analysis suggested that the popular drug rosiglitazone increased the risk for myocardial infarction and had a strong trend to increase the risk for cardiovascular death. Controversy exists over this analysis, its place in context of later studies, and the perspective that we have now. The future use of rosiglitazone based on review of studies and whether it should remain available for clinical use or trials are the subject of this article.
The Role of Statin Therapy in Primary Hyperlipidemia and Mixed Dyslipidemia
Authors: Fazio Sergio ,   Professor of Medicine and Pathology, Atherosclerosis Research Unit, Vanderbilt University Medical Center
Published: October 2015

In the US, ischemic cardiovascular disease (CVD) and stroke combined are the major cause of death for all age groups older than 55 years. Preventive approaches are based on the management of all risk factors and co-morbidities. The management guidelines for the lipid risk factors focus on lowering low-density lipoprotein cholesterol (LDL-C) levels. Statins, which inhibit cholesterol synthesis via blockade of the enzyme 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, are the drug of choice for LDL-C control. Currently, there are three generic and four branded statins. Pitavastatin, the latest statin to be approved by the US Food and Drug Administration (FDA) (2009), has the lipid indications of the other statins but is not indicated for CVD risk reduction. It is available in 1 mg, 2 mg, and 4 mg doses, with the recommended starting dose of 2 mg being equivalent to 20 mg of simvastatin and 10 mg of atorvastatin, and superior to 20 mg of pravastatin. Pitavastatin 2 mg reduces LDL-C levels by 39 %, apolipoprotein B by 31 %, total cholesterol by 28 % and triglycerides by 16 %, and raises high-density lipoprotein cholesterol (HDL-C) by 6 %. In phase III clinical trials, pitavastatin 4 mg decreases LDL-C by up to 45 %. Pitavastatin has a unique metabolism, with little processing by cytochrome P450 (CYP) and none by CYP3A4, and thus it may display less CYP-mediated drug interaction than other statins. However, the FDA has determined that pitavastatin should not be taken with cyclosporine. Pitavastatin should be limited to 1 mg daily with erythromycin and 2 mg daily with rifampin. Preliminary vascular investigations have suggested benefits in line with those obtained by other statins.