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Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease, resulting in hair loss, that affects up to 2% of the general population. The exact pathobiology of AA has still remained elusive, while the common theory is the collapse of the immune privilege of the hair follicle caused by immunological mechanism. Multiple genetic and environment factors contribute to the pathogenesis of AA. There are several clinical treatments for AA, varying from one or multiple well-defined patches to more diffuse or total hair loss of the scalp (alopecia totalis) or hair loss of the entire body (alopecia universalis). The available treatments for AA, such as corticosteroids and other immunomodulators, minoxidil, and contact immunotherapy, are of limited efficacy with a high risk of adverse effects and high recurrence rates, especially for patients with severe AA. Recent insights into the pathogenesis of AA have led to the development of new treatment strategies, such as Janus kinase (JAK) inhibitors, biologics, and several small molecular agents. In addition, modern therapies for AA, including antihistamines, platelet-rich plasma (PRP) injection, and other novel therapies have been well explored. In this review, we discussed the recent advances in the pathogenesis, diagnosis, and treatment of AA.

Vitiligo is a disorder that causes depigmentation of the skin and can impact an individual's quality of life, especially in those with darker skin types due to the contrasting nature. Over the last 30 years, a rise in vitiligo focused research has been observed. Its etiopathogenesis has been described as a complex interaction of various entities encompassing genetics, its downstream effects on the immune system, and subsequently interactions that it holds in conjunction with both exogenous and endogenous oxidative stressors. This review article aims to describe advancements in the etiopathogenesis of vitiligo with a focus on areas with growing evidence.

Rates of diabetes-related complications have declined substantially in the past two decades. However, a large burden of disease persists because of the continued increase in the prevalence of diabetes. Twenty-one years ago, the Diabetes Control and Complications Trial (DCCT) showed that intensive glycemic control could reduce the microvascular complications of type 1 diabetes mellitus. 1 Subsequent studies showed that macrovascular and microvascular complications could be substantially reduced with tight control of glucose levels, blood pressure, and lipid levels in adults with type 2 diabetes. 2 – 5 Collectively, these studies focused attention on diabetes as a public health problem, with a course that could be altered by a combination of changes in clinical care (e.g., intensive management of risk factors), the health system (e.g., organization of care), health promotion (e.g., support for . . .

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

OBJECTIVE: Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS: We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS: Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10-26), HFE (rs1800562/P = 2.6 x 10-20), TMPRSS6 (rs855791/P = 2.7 x 10-14), ANK1 (rs4737009/P = 6.1 x 10-12), SPTA1 (rs2779116/P = 2.8 x 10-9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10-9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 x 10-54), MTNR1B (rs1387153/P = 4.0 x 10-11), GCK (rs1799884/P = 1.5 x 10-20) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10-18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS: GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c.

This study updates previous estimates of the economic burden of diagnosed diabetes and quantifies the increased health resource use and lost productivity associated with diabetes in 2012. The study uses a prevalence-based approach that combines the demographics of the U.S. population in 2012 with diabetes prevalence, epidemiological data, health care cost, and economic data into a Cost of Diabetes Model. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, insurance coverage, medical condition, and health service category. Data sources include national surveys, Medicare standard analytical files, and one of the largest claims databases for the commercially insured population in the U.S. The total estimated cost of diagnosed diabetes in 2012 is $245 billion, including $176 billion in direct medical costs and $69 billion in reduced productivity. The largest components of medical expenditures are hospital inpatient care (43% of the total medical cost), prescription medications to treat the complications of diabetes (18%), antidiabetic agents and diabetes supplies (12%), physician office visits (9%), and nursing/residential facility stays (8%). People with diagnosed diabetes incur average medical expenditures of about $13,700 per year, of which about $7,900 is attributed to diabetes. People with diagnosed diabetes, on average, have medical expenditures approximately 2.3 times higher than what expenditures would be in the absence of diabetes. For the cost categories analyzed, care for people with diagnosed diabetes accounts for more than 1 in 5 health care dollars in the U.S., and more than half of that expenditure is directly attributable to diabetes. Indirect costs include increased absenteeism ($5 billion) and reduced productivity while at work ($20.8 billion) for the employed population, reduced productivity for those not in the labor force ($2.7 billion), inability to work as a result of disease-related disability ($21.6 billion), and lost productive capacity due to early mortality ($18.5 billion). The estimated total economic cost of diagnosed diabetes in 2012 is $245 billion, a 41% increase from our previous estimate of $174 billion (in 2007 dollars). This estimate highlights the substantial burden that diabetes imposes on society. Additional components of societal burden omitted from our study include intangibles from pain and suffering, resources from care provided by nonpaid caregivers, and the burden associated with undiagnosed diabetes.

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and, globally, the quality of diabetes management remains uneven. This Seminar discusses current progress in epidemiology, pathology, diagnosis, and treatment of type 1 diabetes, and prospects for an improved future for individuals with this disease.

To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report. The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions. Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012. The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.

Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.

The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure to volatile organic compounds (VOC) present in the environment. Chronic inflammation due to immune breakdown and malfunctioning of the immune system has been projected to play a major role in the initiation and progression of autoimmune disorders. Macrophages, major phagocytes involved in the regulation of chronic inflammation, are a major target of VOC. Excessive and prolonged activation of immune cells (T and B lymphocytes) and overexpression of the master pro-inflammatory constituents [cytokine and tumor necrosis factor-alpha, together with other mediators (interleukin-6, interleukin-1, and interferon-gamma)] have been shown to play a central role in the pathogenesis of autoimmune inflammatory responses. The function and efficiency of the immune system resulting in immunostimulation and immunosuppression are a result of exogenous and endogenous factors. An autoimmune disorder is a by-product of the overproduction of these inflammatory mediators. Additionally, an excess of these toxicants helps in promoting autoimmunity through alterations in DNA methylation in CD4 T cells. The purpose of this review is to shed light on the possible role of VOC exposure in the onset and progression of autoimmune diseases.