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Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

2 Abstract 2.1 Participating professional associations and organisations These guidelines for the diagnosis and treatment of varicose veins were prepared under the guidance of the Deutsche Gesellschaft für Phlebologie e. V. (DGP) in cooperation with the Deutsche Gesellschaft für Gefäßchirurgie und Gefäßmedizin—Gesellschaft für operative, endovaskuläre und präventive Gefäßmedizin e. V. (DGG), the Deutschen Gesellschaft für Angiologie, Gesellschaft für Gefäßmedizin e. V. (DGA), the Deutsche Dermatologischen Gesellschaft (DDG), the Deutsche Gesellschaft für Dermatochirurgie e. V. (DGDC), the Berufsverband der Phlebologen e. V. (BVP), and the Arbeitsgemeinschaft der niedergelassenen Gefäßchirurgen Deutschlands e. V. (ANG). This updated 2018/2019 version is based on the guidelines agreed and drafted by the same associations in 2004 and 2009, and it was adopted by the Boards of the participating professional associations on 30 April 2019. 2.2 Development stage of the guidelines These guidelines are based on a structured consensus process, drawing on published data to create consensus-based guidelines at development stage S2k. 2.3 Delegates of the professional associations See: https://www.awmf.org/uploads/tx_szleitlinien/037-018l_S2k_Varikose_Diagnostik-Therapie_2019-07.pdf. 2.4 Selected literature The recommendations are based on the same publications used in previous versions and a systematic literature review carried out on 21 July 2016 in the German Institute for Vascular Public Health Research (DIGG). The review included randomised studies, meta-analyses, and controlled studies. The literature search was carried out in the Medline and PubMed databases with the following search fields in German and/or English: sclerotherapy, endovenous thermal ablation, mechanochemical ablation, cyanoacrylate glue, surgical procedures (stripping), and diagnosis, prognosis, and postoperative care of varicose veins. A manual search was carried out for later publications up to December 2018.

Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Background: The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. Methods: We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise cooccurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease–disease interrelationships. Results: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease–disease interrelationships was noted in all three lymphatic categories when compared to the control population.

Recommendations: 1.1 Evidence on the safety of liposuction for chronic lipoedema is inadequate but raises concerns of major adverse events such as fluid imbalance, fat embolism, deep vein thrombosis, and toxicity from local anaesthetic agents. Evidence on the efficacy is also inadequate, based mainly on retrospective studies with methodological limitations. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page. 1.2 Further research should report: • patient selection, including age, effects of hormonal changes (which should include effects seen during puberty and menopause) and the severity and site of disease • details of the number and duration of procedures, the liposuction technique used (including the type of anaesthesia and fluid balance during the procedure), and any procedure-related complications • long-term outcomes, including weight and body mass index changes • patient-reported outcomes, including quality of life. 1.3 Patient selection should be done by a multidisciplinary team, including clinicians with expertise in managing lipoedema. 1.4 The procedure should only be done in specialist centres by surgeons experienced in this procedure.

The Polycystic ovarian syndrome is a feature of the various menstrual cycles, infertility, hormonal irregularities, and hyperandrogenism. Insulin resistance, lipedema and hyperandrogenism are the most widespread endocrine disorder in PCOS. Most half of women with PCOS suffer from hirsutism, weight gain, metabolic syndrome, insulin resistance, hypothyroidism, and dyslipidemia. The Aim of the Study is to measure thyroid function, especially hypothyroidism in women with the polycystic ovarian syndrome and its association with insulin resistance. It also aims to estimate the effect of hypothyroidism on the level of each of the following biochemical parameters: lipid profile, glucose, insulin, anti mullerain hormones, sex hormone and thyroid disorders frequency (hypothyroidism) in PCOS. Subjects, Materials and Methods: This study was performed on patients in the outpatient clinics of the Obstetrics, Gynecology and Infertility Clinic and at the al-Yarmouk Teaching Hospital in 2020, and it included 30 (control group) and 70 patients, including 35 euthyroid PCOS and 35 hypothyroidism PCOS (PCOS group), in the age group 15-45 years. Thyroid hormone levels Thyroxine (FT3, FT4) and Thyroid Stimulating Hormone (TSH), Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Testosterone, Progestogen, Estradiol (E2), Anti Mullerian Hormones (AMH), Thyroperoxidase Anti Bodies (anti TPO), Insulin were measured by using a device cobas e411, and Lipid profile and Glucose by using a device cobas c311. Results: There was an increase in TSH levels, a decrease in thyroxine, an increase in lipid profile levels, an increase in the sex hormones levels, increase glucose and insulin resistance which is a sign of diabetes type 2. However, the reverse is noticed in the relation of hypothyroidism on PCOS with weight gain, lipids, insulin resistance, androgynism and hirsutism. The most frequent thyroid disorders affecting PCOS in this study were found to be autoimmune thyroiditis and hypothyroidism. Conclusions: More than half of the women with PCOS suffer from hypothyroidism, compared to the normal women. As it was observed that dyslipidemia, weight gain, hirsutism, insulin resistance and sex hormones were more in hypothyroidism PCOS women compared to normal control subjects. We also concluded that PCOS and hypothyroidism are interrelated, as the presence of either is a cause of the other and that means the PCOS is more than just oligomenorrhea, amenorrhea, or infertility.

Background: An adequate dietary energy supply is particularly important in patients with lipedema as it promotes weight and fat loss. Accurate estimation of resting metabolic rate (RMR) allows implementing a proper calorie restriction diet in patients with lipedema. Therefore, an accurate assessment of energy demand in patients with lipedema is crucial in clinical practice. Our study aimed to compare actual resting metabolic rate (aRMR) with predicted resting metabolic rate (pRMR) in women with lipedema and to determine the association between individual anthropometric measurements and aRMR.Methods: A total of 108 women diagnosed with lipedema were enrolled in the study. aRMR was measured by indirect calorimetry (IC) using FitMate WM metabolic system (Cosmed, Rome, Italy). pRMR was estimated with predictive equations and BIA. All anthropometric measurements were based on BIA (bioelectric impedance analysis).Results: The mean aRMR in the study group was 1705.2 ± 320.7 kcal/day. Most methods of predicted RMR measurement used in our study significantly underpredicted aRMR in patients with lipedema. We reported statistically significant high correlations between all anthropometric measurements and aRMR/pRMR and a moderate correlation between visceral fat level (VFL) and aRMR. Conclusions: aRMR in patients with lipedema calculated with predictive equations was significantly lower than aRMR measured with other methods. This study found the agreement of predictive equations compared to IC is low (<60%). Fat-free mass (FFM) is a stronger determinant of RMR in patients with lipedema than fat mass.

PURPOSE OF REVIEW: The regulation of blood pressure is conventionally conceptualised into the product of "circulating blood volume" and "vasoconstriction components". Over the last few years, however, demonstration of tissue sodium storage challenged this dichotomous view. RECENT FINDINGS: We review the available evidence pertaining to this phenomenon and the early association made with blood pressure; we discuss open questions regarding its originally proposed hypertonic nature, recently challenged by the suggestion of a systemic, isotonic, water paralleled accumulation that mirrors absolute or relative extracellular volume expansion; we present the established and speculate on the putative implications of this extravascular sodium excess, in either volume-associated or -independent form, on blood pressure regulation; finally, we highlight the prevalence of high tissue sodium in cardiovascular, metabolic and inflammatory conditions other than hypertension. We conclude on approaches to reduce sodium excess and on the potential of emerging imaging technologies in hypertension and other conditions.

Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart failure, end-stage liver disease, chronic kidney disease, and nephrotic syndrome. Diuretics are the cornerstone of therapy for volume overload and comprise several classes whose mechanisms of action, pharmacokinetics, indications, and adverse effects are essential principles of nephrology. Loop diuretics are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders. Separately, clinical trials highlight improved outcomes in some states of volume overload, such as loop diuretics and sodium/glucose cotransporter 2 inhibitors in patients with congestive heart failure. Resistance to diuretics is a frequent, multifactorial clinical challenge that requires creative and physiology-based solutions. In this installment of AJKD's Core Curriculum in Nephrology, we discuss the pharmacology and therapeutic use of diuretics in states of volume overload and strategies to overcome diuretic resistance.

El lipedema es un trastorno crónico que se presenta en mujeres durante la pubertad u otros momentos de cambios hormonales como en el embarazo o la menopausia.  Es caracterizado por una obesidad desproporcionada de las extremidades, especialmente en caderas y piernas, asociado a hematomas con mínimo trauma y dolor espontáneo o inducido por presión. Usualmente es mal diagnoticado e infratratado y suele confundirse con otras enfermedades como la obesidad y linfedema. Su causa aún se sigue estudiando, existen hipótesis sobre su origen poligenético regulado por los estrógenos, por el inicio de la enfermedad en etapas de cambio hormonal y debido a que se presenta mayormente en mujeres. Los tratamiento para el lipedema se basa en seis pilares: 1) Fisioterapia-ejercicios, 2) Terapia compresiva, 3) Control de peso, 4) Liposucción, 5) Terapia psicosocial-6) Automanejo.

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

Lymphatic drainage is the main form of therapy for lymphedema, as it affects the pathophysiology of this clinical condition. The two main objectives of lymphatic drainage are the formation and drainage of lymph. In recent years, Godoy & Godoy developed a novel concept of mechanical lymphatic drainage involving a device denominated RAGodoy®, which performs passive exercises of the lower and upper limbs as a form of lymphatic drainage. The aim of the present study was to address the concept of this therapy as well as perform a literature review on its forms of use and the results obtained. All studies analyzed show that this technique used as monotherapy enables the treatment of lymphedema, but superior results are achieved when combined with compression mechanisms.

Background: There is insufficient clear epidemiological and clinical knowledge about lymphedema patient’s population in Mexico, this limits its investigation. The objective of this study is to present basic lymphedema epidemiological data and its clinical characteristics based on the analysis of lymphedema patients’ data collected from a specialized rehabilitation clinic in Mexico. Methods: This is a cohort study developed between 2015 and 2021. The study was carried ou in a private clinic specialized in oncological and peripheral vascular patients’ rehabilitation. Clinical assessments and interviews were performed to collect each case’s clinical history, considering its medical characteristics, physical activity and functionality and socio-demographic information, classified in a matrix, and later statistically evaluated. Results: Among 446 lymphedema patients, gender distribution was represented by 81% female and 19% male with a mean age of 50.5 years (±44.5). The population was categorized into the following three different study groups according to diagnosis: Cancer-Related Lymphedema (CRL), Non-Cancer-Related Secondary Lymphedema (NCRSL) and Primary Lymphedema. 60.08% of the patients had CRL; 25.11% had NCRSL and 14.79% had Primary Lymphedema. Among the patients with CRL, 81% of them corresponded to breast cancer diagnosis, the rest were associated to 19 different cancer diagnoses. The most prevalent diagnosis was breast CRL 48.6%; phlebolymphedema 19.4%; congenital and praecox lymphedema 14.1%; lipo-lymphedema 4.8%. The BMI of 64% of the patients ranged in overweight and obesity. 37.6% of patients reported that had experienced pain in limbs affected by lymphedema and 45% of all patients reported some disability to perform one or more activities associated to their limb volume or limb discomfort. 82% of patients had no physical activity or performed less physical activity than what is suggested to their population group’s recommendation. Conclusion: This study stablishes a precedent on reporting the broadest available epidemiological and clinical data of lymphedema in Mexico. Further studies are needed to report with a higher precision the epidemiological, clinical, and demographical data about each etiological group for a better understanding of lymphedema in Mexico and Latin America.

Background: Lipedema is a chronic and progressive adipose tissue disorder that causes significant morbidity and negatively influences mental health and quality of life, and increases the risk of depression, anxiety, and eating disorders. One construct of relevance to better understanding psychological disorders is emotion regulation (ER). Therefore, the aim of this study is to investigate the difficulties in ER among lipedema patients compared to healthy people without lipedema. Methods: This cross-sectional study assessed differences in ER and anxiety between two groups: 26 female patients with lipedema and 26 sex- and age-matched healthy controls. The Difficulties in Emotion Regulation Scale (DERS) assessed emotional regulation across six dimensions: Impulse control, goal-directed behavior, awareness, clarity, non-acceptance, and strategies. Anxiety was assessed by the Hamilton Anxiety Scale (HAM-A). ANOVA assessed differences in measures between lipedema and healthy control groups. Results: Lipedema patients presented with significantly more difficulties in ER and a higher level of anxiety than those without lipedema. Specifically, the lipedema group showed higher and significant differences in total DERS and anxiety scores and all DERS subscales scores compared to those without lipedema. Conclusions: Lipedema patients showed significant difficulties with ER, and were associated with anxiety symptoms, indicating that ER difficulties may play a role in developing emotional disorders, such as anxiety, for patients with lipedema. The health care provider should pay more attention to ER difficulties and psychological status among lipedema patients.

Lipedema patients suffer not only from visual stigma but also reduction in their quality of life through pain and performance loss in daily life. In clinical practice, it is still difficult to reliably diagnose the disease. This study aims to provide further insights into the characteristics of lipedema patients of all stages and provide a baseline prior to surgery for a surgical treatment evaluation by means of patient-reported outcome measures. Methods: Patients completed a lipedema-specific questionnaire containing 50 items, the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). The data were analyzed using SPSS statistics 27. Patients who had already received liposuction were excluded. Results: Five hundred and eleven patients were included, of whom 337 completed the PHQ9 and 333 completed the WHOQOL-BREF questionnaires. The general characteristics of lipedema patients, especially the daily symptoms, are described. Previous observations, such as the frequent occurrence of hypothyroidism and the low rate of type 2 diabetes, were confirmed. Over 49% suffer from severe impairments in their jobs, whereby the disease shows a familial accumulation. The results of the WHOQOL-BREF and the PHQ-9 suggest a high level of mental stress. Discussion: As surgical intervention in lipedema patients is gaining traction, its effects should be well-documented. Therefore, a comprehensive baseline needs to be established prior to surgical treatment. The psychological components are just as important as the inclusion of daily impairments.