Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod.
multiple sclerosis; oral drug; clinical trial; treatment
Since it was first described nearly three decades ago, endoscopic papillectomy (EP) has been utilized as a less invasive, alternative therapy for adenoma of the major duodenal papilla. In this article, we review the recent advances in EP, especially those pertaining to endoscopic ultrasonography (EUS), intraductal ultrasonography (IDUS), and pancreatic stent placement for the prevention of postpapillectomy pancreatitis. Because EUS and IDUS have similar diagnostic accuracies, either modality can be used for the preprocedural evaluation of ampullary tumors. Nevertheless, further technical refinements are required for a more precise evaluation. Given the paucity of data on the usefulness of EUS and/or IDUS during follow-up after EP, a well-designed study is warranted. Furthermore, pancreatic stent placement appears to have a protective effect against postpapillectomy pancreatitis; however, a prospective, randomized, controlled study with a larger number of patients is needed to assess this finding. Moreover, since pancreatic stent placement after EP is not always successful, various novel techniques have been developed to ensure reliable stent placement. Despite the recent advances in EP, further technical refinements and studies are needed to confirm their efficacy.
Ampulla of Vater; Ampullary tumors; Endoscopic resection; Endoscopic papillectomy
Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.
Autoimmune diseases; Systems biology; Multi-omics; Biomarker; Translational research; Network analysis
The image quality management of bone mineral density (BMD) is the responsibility and duty of radio-technologists who carry out examinations. However, inaccurate conclusions due to the lack of understanding and ignorance regarding the methodology of image quality management can be a fatal error to patients. The accuracy and precision of BMD measurement must be maintained at the highest level so that actual biological changes can be detected with even slight changes in BMD. Accuracy and precision should be continuously preserved for image quality of machines. Those factors will contribute to ensure the reliability of BMD examination. The enforcement of proper quality control of radiologists performing BMD inspections which brings about the durability extensions of equipment and accurate results of calculations will help the assurance of reliable inspections.
Bone density; Densitometry; Dual-energy X-ray absorptiometry; Precision; Quality control
Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFBP-3 results in glucose intolerance, and insulin resistance. IGFBP-3 knockout (KO) mice exhibited normal insulin level and glucose response after glucose challenge. More recent study in IGFBP-3 KO mice with a high-fat diet demonstrated that IGFBP-3 KO mice exhibited elevated fasting glucose and insulin, but normal response to glucose challenge, suggesting that IGFBP-3 KO mice may induce insulin resistance even though preserved insulin sensitivity. In vitro and in vivo studies using 3T3-L1 adipocytes and rat, IGFBP-3 induced insulin resistance by inhibiting glucose uptake. In contrast, the reduced levels of IGFBP-3 in obesity might induce insulin resistance by suppression of IGFBP-3's anti-inflammatory function, suggesting IGFBP-3 has a protective effect on insulin resistance. Also, proteolysis of IGFBP-3 might contribute to the insulin resistance in obesity and type 2 diabetes mellitus. In addition, IGFBP-3 inhibited adipocyte differentiation, suggesting IGFBP-3 may contribute to the insulin insensitivity. Taken together, it is not yet certain that IGFBP-3 has a protective effect or enhancing effect on insulin resistance, and more studies will be needed to clarify the roles of IGFBP-3 in metabolic regulation.
Insulin-like growth factor binding protein-3; Insulin resistance; Adipocytes; Metabolism
Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.
International Digestive Endoscopy Network (IDEN) is an international meeting covering scientific subjects of diverse topics about upper gastrointestinal (GI) endoscopy, colonoscopy, endoscopic ultrasonography, and PB endoscopy. IDEN is organized by Korean Society of Gastrointestinal Endoscopy and the Korean Gastrointestinal Endoscopy Research Foundation, and took its first step in 2011 in Seoul, Korea. IDEN inaugurated a new era of diagnostic and therapeutic GI endoscopy. IDEN 2012 was designed to offer participants from all over the world with opportunities to share up-to-date knowledge about basic and clinical aspects of GI endoscopy and to engage in in-depth discussion with worldwide well-known experts. During the 2 days of meeting, there were 62 invited lectures, 28 case-based discussions, 20 video lectures, and 6 breakfast with the experts. There were a total of 598 participants registered from 12 countries, including Asian countries, Europe, and USA as well as Korea.
International Digestive Endoscopy Network; Korean Society of Gastrointestinal Endoscopy; Endoscopy
Hyponatremia is the most common electrolyte disorder in hospitalized patients. Many studies documented that it was related to increased morbidity and mortality in patients with congestive heart failure, liver cirrhosis, and neurologic diseases. Although knowledge of hyponatremia has been cumulated, the optimal management of hyponatremia remains incompletely established in clinical practice because of the diversity of underlying disease states, and its multiple causes with differing pathophysiologic mechanisms. Since vasopressin receptor antagonists have unique aquaretic effect to selectively increase electrolytes-free water excretion, clinicians could apply a more effective method to treat hyponatremia. Tolvaptan has significant evidence that it improves serum sodium levels in patients with euvolemic or hypervolemic hyponatremia related with heart failure, cirrhosis or syndrome of inappropriate anti-diuretic hormone. Tolvaptan has acceptable safety and tolerability for long-term usage in chronic hyponatremia, and the beneficial effects on serum Na+ occurred in patients with both mild and marked hyponatremia.
tolvaptan; hyponatremia; arginine vasopressin receptors
Neuromyelitis optica (NMO) is an idiopathic inflammatory disorder of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. In Asia, NMO has long been considered a subtype of multiple sclerosis (MS). However, recent clinical, pathological, immunological, and imaging studies have suggested that NMO is distinct from MS. This reconsideration of NMO was initially prompted by the discovery of a specific antibody for NMO (NMO-IgG) in 2004. NMO-IgG is an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS; hence, it was named anti-AQP4 antibody. Since it demonstrated reasonable sensitivity and high specificity, anti-AQP4 antibody was incorporated into new diagnostic criteria for NMO.The spectrum of NMO is now known to be wider than was previously recognized and includes a proportion of patients with recurrent, isolated, longitudinally extensive myelitis or optic neuritis, and longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease or with brain lesions typical of NMO. In this context, a new concept of "NMO spectrum disorders" was recently introduced. Furthermore, seropositivity for NMO-IgG predicts future relapses and is recognized as a prognostic marker for NMO spectrum disorders. Humoral immune mechanisms, including the activation of B-cells and the complement pathway, are considered to play important roles in NMO pathogenesis. This notion is supported by recent studies showing the potential pathogenic role of NMO-IgG as an initiator of NMO lesions. However, a demonstration of the involvement of NMO-IgG by the development of active immunization and passive transfer in animal models is still needed. This review focuses on the new concepts of NMO based on its pathophysiology and clinical characteristics. Potential management strategies for NMO in light of its pathomechanism are also discussed.
neuromyelitis optica; Devic's disease; neuromyelitis optica spectrum disorder; pathogenesis; diagnosis; management
This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.
Guideline; Prevention; Venous Thromboembolism
Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by inflammation-induced airflow limitation and parenchymal destruction. In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specific dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses. Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age. These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airflow limitation and dynamic hyperinflation. However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes significantly to reduced exercise capacity and poor quality of life in these patients. Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic inflammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density. This review briefly summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the field.
skeletal muscles; chronic obstructive pulmonary disease; diaphragm; quadriceps; fatigue; disuse; atrophy; smoking; exercise
Metabolic acidosis has been considered as one of the reverse epidemiologic factors for the morbidity and mortality in maintenance hemodialysis patients (MHP). Expectedly, in the recent large scale epidemiologic study (The Dialysis Outcome Practice Pattern Study, DOPPS), a mild to moderate degree of predialysis metabolic acidosis has shown better nutritional status and lower relative risk for mortality and hospitalization in MHP. Similarly, another recent study of the largest sample size of MHP of more than 55,000 revealed the lowest unadjusted mortality with mild to moderate degree of predialysis HCO3 levels (17 to 23 mEq/L). However, it was reversed after case-mix and multivariate adjustment, including the malnutrition-inflammation complex syndrome, so that predialysis HCO3 levels of more than 22 mEq/L had a lower death risk. On view of this up-to-date on-going controversy about the optimal acid-base status for MHP, this paper will review the historical and break-through data about the pros and cons of metabolic acidosis published in the clinical human studies of MHP, a special subgroup of chronic kidney disease patients. Based on these results, if possible, we would like to suggest the best practice guideline, particularly, for the optimal predialysis HCO3 level, dialysate HCO3 concentration, and dietary protein intake.
Metabolic acidosis; Hemodialysis
In end-stage renal disease (ESRD) patients regardless of dialysis modes, i.e. maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), potassium (K) homeostasis is regulated primarily via dialysis and extrarenal K regulation in the diverse daily K intake. However, K metabolism has been known to differ greatly between the two main methods of dialysis. Hyperkalemia is a common complication (10-24%) and the most common cause of the death (3-5%) among electrolyte disorders in patients on maintenance HD. On the contrary, hypokalemia (10-36%) is responsible for a rather common complication and independent prognostic factor on CAPD. Although excessive K intake or inadequate dialysis on maintenance HD and poor nutritional K intake on CAPD are accused without doubts upto 50% of ESRD patients as a primary cause of the K-imbalance, i.e. hyperkalemia on HD and hypokalemia on CAPD, other contributory factors including certain medications and unknown causes remain still to be resolved. Accordingly, the effects of medications as another source of K-imbalance on HD with RAS blockades and beta blockers as well as those of conventional and glucose-free dialysates (Icodextrin) for internal K-redistribution on CAPD were evaluated with reviewing the literatures and our data. Furthermore, new developments in the clinical managements of hyperkalemia on HD following the exclusion of pseudohyperkalemia before the initiation of dialysis were suggested, especially, by the comparison of the effects between mono- and dual-therapy with medications for transcellular K shifting in the emergent situation. Also, the intraperitoneal K administration via conventional glucose-containing (2.5%) and glucose-free dialysates (Icodextrin) as a specific route of K-supplementation for hypokalemia on CAPD was examined for its efficiency and the degree of intracellular K shift between these two different types of dialysates.
Hyperkalemia; Hypokalemia; Hemodialysis; Continuous ambulatory peritoneal dialysis