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1.
Purpose of Review
As the ongoing epidemic of adult and childhood obesity grows, it puts a greater burden on individuals and the healthcare system due to increased prevalence of obesity-associated diseases. An important area that has gained much attention recently is the sex and gender difference related to obesity and associated complications. Basic science and clinical studies have now improved our understanding of obesity and have discovered adipose tissue biology to be key in metabolism.Recent Findings
There is evidence related to the sex dichotomy in obesity in a variety of areas including adipocyte function, sex hormone effects, genetics, and metabolic inflammation leading to critical differences in adipose tissue biology.Summary
The sex and gender difference in adipose tissue is a factor that should be considered when studying an individuals’ risk for obesity and metabolic dysfunction. This understanding is important for strategizing treatment and prevention measures.2.
Purpose of review
This article focuses on recent progress in understanding the genetics of lipodystrophy syndromes, the pathophysiology of severe metabolic abnormalities caused by these syndromes, and causes of severe morbidity and a possible signal of increased mortality associated with lipodystrophy. An updated classification scheme is also presented.Recent findings
Lipodystrophy encompasses a group of heterogeneous rare diseases characterized by generalized or partial lack of adipose tissue and associated metabolic abnormalities including altered lipid metabolism and insulin resistance. Recent advances in the field have led to the discovery of new genes associated with lipodystrophy and have also improved our understanding of adipose biology, including differentiation, lipid droplet assembly, and metabolism. Several registries have documented the natural history of the disease and the serious comorbidities that patients with lipodystrophy face. There is also evolving evidence for increased mortality rates associated with lipodystrophy.Summary
Lipodystrophy syndromes represent a challenging cluster of diseases that lead to severe insulin resistance, a myriad of metabolic abnormalities, and serious morbidity. The understanding of these syndromes is evolving in parallel with the identification of novel disease-causing mechanisms.3.
Purpose of Review
Obesity is currently seen in epidemic proportions globally and is one of the largest contributors to the development of NAFLD. The spectrum of NAFLD, particularly the progressive forms of NASH, is likely to become the leading cause of liver disease in the next decade.Recent Findings
Soluble molecules, encoded by the stomach tissue, have been shown to have pleiotropic effects in both central and peripheral systems involved in energy homeostasis and obesity regulation. As such, the stomach is one of the important players in the complex, multi-system deregulation leading to obesity and NAFLD.Summary
The understanding of the stomach tissue as an active endocrine organ that contributes to the signaling milieu leading to the development of obesity and NAFLD is crucial.4.
Purpose of Review
Prevalence and outcome differences between women and men with pulmonary arterial hypertension (PAH) raise questions about the role of sex hormones in disease pathobiology. This review will summarize the current understanding of sex and sex hormone pathways and their influence on heart-lung function in health and in disease.Recent Findings
Female sex has been shown to be a risk factor for the development of PAH, but women have improved survival compared to men with PAH. These paradoxical observations are likely driven in part by complex sex hormone signaling and processing pathways and their interaction with the pulmonary vasculature and the right ventricle. These relationships may vary depending on an individual’s underlying sex, age, and/or genetic substrate.Summary
The study of the connections between sex, sex hormones, the pulmonary circulation, and the right ventricle may improve our understanding of disease epidemiology and outcomes and lead to new treatment strategies for PAH.5.
Thomas Laeger Christian Baumeier Ilka Wilhelmi Josefine Würfel Anne Kamitz Annette Schürmann 《Diabetologia》2017,60(11):2274-2284
Aims/hypothesis
Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes.Methods
Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week. Mice were treated subcutaneously with PBS or FGF21 to assess changes in glucose homeostasis, energy expenditure, food intake and other metabolic endpoints.Results
FGF21 treatment prevented islet destruction and the onset of hyperglycaemia, and improved glucose clearance. FGF21 increased energy expenditure by inducing browning in subcutaneous white adipose tissue. However, as a result of a compensatory increased food intake, body fat did not decrease in response to FGF21 treatment, but exhibited elevated Glut4 expression.Conclusions/interpretation
FGF21 prevents the onset of diet-induced diabetes, without changing body fat mass. Beneficial effects are mediated via white adipose tissue browning and elevated thermogenesis. Furthermore, these data indicate that obesity does not induce FGF21 resistance in NZO mice.6.
Purpose of Review
To report on current and emerging trends in the use of third-line therapies for non-neurogenic overactive bladder (OAB).Recent findings
The use of third-line therapies for OAB has been steadily increasing, but it appears that only a small percentage of OAB patients receive them. Recent research has found an increased risk of dementia associated with cumulative use of anticholinergic medications, including OAB antimuscarinic medications. Cost-effective analyses suggest that these third-line therapies may be worth considering prior to medications.Summary
Research and efforts to improve adherence to current OAB guidelines are needed to increase their use by patients with refractory OAB. Whether or not the therapies we presently consider third line should actually be second line for some of our patients remains to be determined.7.
Daniela R. Crousillat Nasrien E. Ibrahim 《Current treatment options in cardiovascular medicine》2018,20(11):88
Purpose of review
Heart failure (HF) is prevalent among women and remains a leading cause of morbidity and mortality in the United States. Currently, 3 million women live with HF and the prevalence is projected to continue to increase. The purpose of this review is to highlight sex differences in the use and response to evidence-based pharmacological, device, and advanced HF therapies, as well as explore emerging areas of research in sex differences in the treatment of HF.Recent findings
Under-representation of women in clinical HF trials has limited our understanding of sex-related differences in the treatment and outcomes of HF.Summary
Important sex differences exist in the use of evidence-based HF therapies and clinical response among women with HF. In general, women tend to obtain the same clinical benefit from evidence-based HF drug and device therapies, but the utilization rates of guideline-directed medical therapies remain poor compared to men. Future research efforts should focus on increasing the enrollment of women in HF trials to help gain helpful insight into sex-specific differences in treatment effects and subsequent clinical outcomes.8.
Purpose of Review
The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We present some of the current cardiovascular disease models utilizing genome editing and patient-derived iPSCs.Recent Findings
The incorporation of genome-editing and iPSC technologies provides an innovative research platform, providing novel insight into human cardiovascular disease at molecular, cellular, and functional level. In addition, genome editing in diseased iPSC lines holds potential for personalized regenerative therapies.Summary
The study of human cardiovascular disease has been revolutionized by cellular reprogramming and genome editing discoveries. These exceptional technologies provide an opportunity to generate human cell cardiovascular disease models and enable therapeutic strategy development in a dish. We anticipate these technologies to improve our understanding of cardiovascular disease pathophysiology leading to optimal treatment for heart diseases in the future.9.
Sridharan Raghavan Mark C. Pachucki Yuchiao Chang Bianca Porneala Caroline S. Fox Josée Dupuis James B. Meigs 《Journal of general internal medicine》2016,31(10):1127-1133
BACKGROUND
Obesity and diabetes family history are the two strongest risk factors for type 2 diabetes (T2D). Prior work shows that an individual’s obesity risk is associated with obesity in social contacts, but whether T2D risk follows similar patterns is unknown.OBJECTIVE
We aimed to estimate the relationship between obesity or diabetes in an individual’s social contacts and his/her T2D risk. We hypothesized that obesity and diabetes in social contacts would increase an individual’s T2D risk.DESIGN
This was a retrospective analysis of the community-based Framingham Offspring Study (FOS).PARTICIPANTS
FOS participants with T2D status, height and weight, and at least one social contact were eligible for this study (n?=?4797 at Exam 1). Participants’ interpersonal ties, cardiometabolic and demographic variables were available at eight exams from 1971 to 2008, and a T2D additive polygenic risk score was measured at the fifth exam.MAIN MEASURES
Primary exposures were T2D (fasting glucose?≥?7 mmol/L or taking diabetes medications) and obesity status (BMI?≥?30 kg/m2) of social contacts at a prior exam. Primary outcome was incident T2D in participants.KEY RESULTS
Incident T2D was associated with having a social contact with diabetes (OR 1.32, p?=?0.004) or with obesity (OR 1.21, p?=?0.004). In stratified analyses, incident T2D was associated with diabetes in siblings (OR 1.64, p?=?0.001) and obesity in spouses (OR 1.54, p =?0.0004). The associations between diabetes and obesity in social contacts and an individual’s incident diabetes risk were stronger in individuals with a high diabetes genetic risk score.CONCLUSIONS
T2D and obesity in social contacts, particularly siblings and spouses, were associated with an individual’s risk of incident diabetes even after accounting for parental T2D history. Assessing risk factors in an individual’s siblings and spouses can inform T2D risk; furthermore, social network based lifestyle interventions involving spouses and siblings might be a novel T2D prevention approach.10.
Background
The Affordable Care Act (ACA) of 2010 incentivized states to expand eligibility for their Medicaid programs. Many did so in 2014, and there has been great interest in understanding the effects of these expansions on access to health care, health care utilization, and population health.Objective
To estimate the longer-term (three-year) impact of Medicaid expansions on insurance coverage, access to care, preventive care, self-assessed health, and risky health behaviors.Design
A difference-in-differences model, exploiting variation across states and over time in Medicaid expansion, was estimated using data from the Behavioral Risk Factor Surveillance System (BRFSS) for 2010–2016.Participants
Low-income childless adults aged 19–64 years in the BRFSS.Main Measures
Outcomes included insurance coverage, access to care, several forms of preventive care (e.g., routine checkups, flu shots, HIV tests, dental visits, and cancer screening), risky health behaviors (e.g., smoking, alcohol abuse, obesity), and self-assessed health.Key Results
The previously documented benefits of Medicaid expansions on insurance coverage, access to care, preventive care, and self-assessed health have persisted 3 years after expansion. There was no detectable effect on risky health behaviors.Conclusions
The Affordable Care Act was motivated in part by a desire to increase health insurance coverage, improve access to care, and increase use of preventive care. The Medicaid expansions facilitated by the ACA are helping to achieve those objectives, and the benefits have persisted 3 years after expansion.11.
Purpose of review
Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disseminated vasculitis associated with extravascular granulomas in patients suffering from asthma and tissue eosinophilia. Current therapies to achieve remission and prevent relapse include glucocorticoids and immunosuppressants like cyclophosphamide.Recent findings
With the right treatment, clinical prognosis is favorable, so concerted efforts have been made in recent years to find new alternatives for treating severe EGPA. Monoclonal antibodies such as omalizumab, rituximab, and mepolizumab are among these new options.Summary
This review summarizes the pathogenesis and clinical manifestations of EGPA and critically examines current and emerging therapies.12.
Purpose of Review
The goal of this review is to provide an up-to-date approach to diagnosis and management of patients with central nervous system (CNS) vasculitis.Recent Findings
Challenges in diagnosis of CNS vasculitis still exist due to the broad differential diagnosis and generally nonspecific initial clinical manifestations. Differentiation between primary angiitis of the CNS (PACNS) and secondary causes is important in guiding management. Recent longitudinal cohort studies have improved our understanding of PACNS. Advances in neuroimaging and molecular testing have enhanced diagnostic decision-making. Therapy remains largely empiric, guided by observational data. Despite the limited use of targeted therapies, glucocorticoids and cyclophosphamide remain the mainstays of therapy in PACNS.Summary
Securing a diagnosis through a careful, team-based approach with emphasis on ruling out possible mimics is paramount in the management of patients with CNS vasculitis.13.
Purpose of Review
In spite of advances in our understanding of acute heart failure (AHF) and its different phenotypic expressions, AHF management is still centered on volume removal with intravenous diuretics. This narrative review describes the pathophysiology underlying hypertensive AHF and appraises therapies targeting these mechanisms.Recent Findings
Vascular redistribution rather than volume overload may be the primary determinant of elevated cardiac filling pressures and subsequent pulmonary congestion in patients with hypertensive AHF; in these patients, vasodilators should be the predominant treatment. Additional therapy with diuretics in hypertensive AHF should be relegated to the treatment of overt volume overload or persistent congestion in spite of optimized hemodynamics. Intravenous nitroglycerin at high doses can rapidly achieve pulmonary decongestion and reduce downstream critical care needs in these patients. The therapeutic role for synthetic peptides with vasodilator properties has yet to be defined.Summary
Evidence supporting both old and new vasodilator therapies is limited by a paucity of well-designed studies and failure to demonstrate improvement in long-term outcomes. Targeted study of this phenotype of AHF is needed before vasodilator therapies become incorporated into treatment guidelines.14.
Introduction
This publication reviews the function of arginine vasopressin and focuses on the morphologic and functional correlation between the hormone and its effect on stress, the hypophysial–adrenocortical axis, neuroimmune responses, renal function and corticotroph pituitary tumors.Materials and methods
A literature review was performed using various search engines for information regarding the morphology and the multifunctional role of arginine vasopressin.Results
Although a large number of studies were published discussing these interactions, there are several important areas that are still obscure.Conclusion
The questions of how does arginine vasopressin affect the morphology and function of these various areas, and how does the secretion of ACTH and adrenocortical hormones influence the morphology of arginine vasopressin-producing cells and their hormone secretion requires further investigation.15.
Background
Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.Objectives
The psychosocial support given by self-help associations in different phases is evaluated.Materials and methods
Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.Results
On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.Conclusions
The removal of barriers and development of effective structures are overdue.16.
Purpose of Review
Men and women differ in the prevalence, pathophysiology and control rate of hypertension in an age-dependent manner. The renal endothelin system plays a central role in sex differences in blood pressure regulation by control of sodium excretion and vascular function. Improving our understanding of the sex differences in the endothelin system, especially in regard to blood pressure regulation and sodium homeostasis, will fill a significant gap in our knowledge and may identify sex-specific therapeutic targets for management of hypertension.Recent Findings
The current review will highlight evidence for the potential role for endothelin system in the pathophysiology of hypertension within three female populations: (i) postmenopausal women, (ii) women suffering from preeclampsia, or (iii) pulmonary arterial hypertension.Summary
Clinical trials that specifically address cardiovascular and renal diseases in females under different hormonal status are limited. Studies of the modulatory role of gonadal hormones and sex-specific mechanisms on critically important systems involved, such as endothelin, are needed to establish new clinical practice guidelines based on systematic evidence.17.
Background
The prognosis of specific subgroups of patients has been significantly improved by a personalized medicine due to histological differentiation, discovery of new oncogene driver mutations in adenocarcinomas and the introduction of targeted therapies.Objective
Minimally invasive endoscopic methods as well as surgical procedures are available for obtaining histological and cytological material for molecular diagnostics. The various diagnostic options with their advantages and disadvantages are described.Material and methods
A literature search was carried out in PubMed.Results
In every patient it should be possible for clinically practical reasons to perform molecular diagnostic investigations on biopsies, which are as small as possible. Endoscopic transbronchial needle aspiration (TBNA) has a high sensitivity and represents the diagnostic method of choice. If radiologically suspicious mediastinal lymph nodes are present and the cytological result is negative, surgical evaluation is still necessary.Discussion
In the future the aim will be to find further molecular alterations that make a targeted therapy possible and which can be used as prognostic biomarkers or to predict therapy response. Research into entirely noninvasive methods, such as analysis of circulating tumor cells is ongoing.18.
Giovanni B. Gaeta Massimo Puoti Nicola Coppola Teresa Santantonio Raffaele Bruno Antonio Chirianni Massimo Galli 《Infection》2018,46(2):183-188
Aim
This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).Methods
This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.Results
Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.Conclusions
Early treatment with DAA should be offered when available.19.
Purpose of Review
Type 2 diabetes is a growing concern worldwide with increasing incidence in youth. Development of preventive strategies in earlier stages of life is crucial. We aimed to examine epidemiological evidence of early-life exposures and their associations with childhood and later risk of obesity and diabetes, and to discuss potential mechanisms.Recent Findings
Parental obesity and diabetes in the preconception period may influence offspring’s obesity risk via epigenetic mechanisms influencing gametogenesis and early development that could have significant transgenerational effects. A more comprehensive understanding of these effects is needed to identify possible avenues for interventions in both fathers and mothers to be. In addition, current evidence suggests that growth and body weight trajectories in infancy and childhood are useful indicators of later obesity and type 2 diabetes. Moreover, the composition and variations in the microbiome in early life are associated with long-term health and could mediate associations between several early-life exposures and later risk of diseases.Summary
Altogether, the epidemiological evidence supports the need for preconception and early-life interventions to reduce the obesity and diabetes burden in later life.20.
M. G. Pramateftakis P. Hatzigianni D. Kanellos G. Vrakas Th. Tsachalis I. Mantzoros I. Kanellos C. Lazaridis 《Techniques in coloproctology》2010,14(1):63-64