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The objective of this study was to investigate the effect of manual lymphatic drainage (MLD) on the insulin resistance parameter (HOMA-IR), glycated hemoglobin (HbA1c), C-peptide, insulin, fasting plasma glucose (FPG), 2h-post-loadglucose (2h-PG) and the concentration of high-sensitivity C-reactive protein (hsCRP) in patients with abnormal body mass index. The study involved 30 patients, including patients with normal body weight (as a control group; group I; n = 14), overweight patients (group II; n = 9) and obese patients (group III; n = 7). Each patient underwent 10 sessions of MLD therapy, 3 times a week for 30 min. In addition, we measured body mass index (BMI) and waist-to-hip ratio (WHR) and performed body composition analysis as well as biochemical tests before MLD therapy (stage 0') and after MLD therapy (stage 1'). A statistically significant correlation was demonstrated between the concentration of C-peptide, BMI, the amount of visceral adipose tissue (r = 0.87, p = 0.003; r = 0.76, p = 0.003, respectively), and the HOMA-IR index, BMI and the amount of visceral adipose tissue (r = 0.86, p = 0.005; r = 0.84, p = 0.042, respectively), before and after MLD therapy. In overweight patients (group II), a statistically significant (p = 0.041) decrease in the hsCRP level by 2.9 mg/L and a significant (p = 0.050) decrease in the 2h-PG level by 12 mg/dL after the MLD therapy was detected. Moreover, in the group of obese patients (group III), a statistically significant (p = 0.013) decrease in HbA1c level by 0.2% after MLD therapy was demonstrated. Our results indicate that MLD may have a positive effect on selected biochemical parameters, with the most favorable changes in overweight patients. Further studies in a larger number of patients are warranted to confirm our findings, to test in-depth their mechanism, and to investigate clinical benefits of this alternative therapy in patients with abnormal body mass index.

Background The three-dimensional [3D] wound dressings Biobrane® and Epicite are used in the wound management. Fibroblasts are important for successful deep wound healing. The direct effect of Biobrane® and Epicite on human fibroblasts, particularly of juvenile individuals, remains unclear. Therefore, this study compared the survival and growth characteristics of juvenile and adult dermal fibroblasts on Biobrane® and Epicite using different culture models. Method Murine (L929), primary juvenile and adult human fibroblasts were seeded on both materials using two dimensional (2D, slide culture) or 3D culture at the medium-air interface and dynamical rotatory culture. Cell adherence, viability, morphology and actin cytoskeleton architecture were monitored. Scanning electron microscopy (SEM) analyses could be only performed from Biobrane®. Permeability and DNA amount of both materials were tested. Results The majority of all tested fibroblasts species survived on both dressings with no significant differences between 1 and 14 days. Juvenile and adult fibroblasts exerted typical fibroblast morphology with spindle-shaped cell bodies on the materials. SEM visualized morphological differences between murine and human fibroblasts on Biobrane®. Juvenile and adult fibroblasts colonized Biobrane® in rotatory culture after 7 days the most. The Biobrane® rotatory culture of L929 and juvenile fibroblasts showed after 7 days the significantly highest DNA amount. No major gender differences could be observed. Biobrane® had a higher permeability than Epicite. Conclusion Both wound dressing can be colonized by fibroblasts suggesting their high cytocompatibility. Fibroblast survival and morphology on Biobrane® and Epicite depended on the culture system and the fibroblast source.

There are many different causes of leg and foot swelling, some are benign and transient, others can be debilitating and progressive. Correct diagnosis and early treatment is crucial as conservative measures are most effective before the condition is allowed to progress. Current waiting times in the UK National Health Service (NHS) after the Covid-19 pandemic are leading to delays in care for people with chronic leg swelling. Delayed or inadequate treatment for these patients can lead to irreversible tissue damage, an episode of cellulitis, and progression to leg ulceration. There is in addition a significant impact on quality of life associated with living with the pain, anxiety, and reduced mobility. The causes of acute and chronic leg and foot swelling are outlined. Diagnosis and treatment of the common causes of leg and foot swelling in the Western adult population are discussed. The mainstay of treatment for most of these conditions relies on physical therapy and graduated elastic compression garments or elastic Velcro wraps as many do not have a cure.

Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.

Abstract Objectives Lipoedema is a chronic fat disorder involving an excessive abnormal deposition of subcutaneous fat in the thighs, legs, hips and buttocks mainly (Wounds UK, 2017). The importance of healthy eating in lipoedema management has been recognised (Wounds UK, 2017), yet dietary guidelines specific for lipoedema are lacking (Bertsch et al., 2020). The study aimed to investigate the self-reported dietary and lifestyle impact on lipoedema management among a representative lipoedema population in the UK. Methods The study used an online questionnaire that consisted of multiple-choice and open-response questions to collect data on symptoms and diagnostic status of lipoedema and self-reported dietary and lifestyle impact on lipoedema management among participants. The questionnaire was constructed using the Survey Monkey software. The active online survey link was sent to Lipoedema UK's members and contacts via e-mail and also made accessible via the study flyer advertised on Lipoedema UK's website and newsletters. Ethical approval was obtained from the De Montfort University Faculty Research Ethics Committee of Health and Life Sciences prior to the study. Participants had given their consents before starting the survey. Data collection was anonymous. Data were analysed using SPSS v26.0. Results The results showed that 165 out of 257 participants (66.3%) had tried diet as a mean to improve their lipoedema symptoms in the past. Anti-inflammatory diet was reported to be one of the three most effective diets that improved their symptoms (either single or multiple). The other two diets were ketogenic diet and rare adipose disorder diet. Noticeably, 95% of the 257 participants were classified as either overweight or obese based on their Body Mass Index (BMI) measure. And 20% of the participants who tried weight loss diets had found improvements in their lipoedema conditions. Conclusions The study results will help inform the development of future research on finding a dietary solution to effective lipoedema management for the UK lipoedema population. Funding Sources De Montfort University funded the recruitment of a Research Assistant to support part of the data analysis work.

(1) Background: Due to insufficient knowledge of lipoedema, the treatment of this disease is undoubtedly challenging. However, more and more researchers attempt to incorporate the most effective lipoedema treatment methods. When assessing a new therapeutic method, choosing correct, objective tools to measure the therapeutic outcome is very important. This article aims to present possible instruments that may be used in the evaluation of therapeutic effects in patients with lipoedema. (2) Methods: The data on therapeutic outcome measurements in lipoedema were selected in February 2022, using the Medical University of Gdansk Main Library multi-search engine. (3) Results: In total, 10 papers on this topic have been identified according to inclusion criteria. The tools evaluating the therapeutic outcomes used in the selected studies were: volume and circumference measurement, body mass index, waist-to-hip ratio, ultrasonography and various scales measuring the quality of life, the level of experiencing pain, the severity of symptoms, functional lower extremity scales, and a 6 min walk test. (4) Conclusion: The tools currently used in evaluating the effectiveness of conservative treatment in women with lipoedema are: volume and circumference measurement, waist-to-hip ratio, body fat percentage, ultrasonography, VAS scale, quality of life scales (SF-36, RAND-36), symptom severity questionnaire (QuASiL), Lower Extremity Functional Scale and 6 min walk. Choosing a proper tool to measure the treatment outcome is essential to objectively rate the effectiveness of therapeutic method.

Background: Lipedema of lower limbs is characterized by bilateral accumulations of excess adipose tissue starting from the ankle to the hips and buttocks. The studies with lymphoscintigraphy (LSC) and magnetic resonance (MR) lymphography show altered transport index and enlarged lymphatic vessels (LVs). Our studies aimed to investigate the superficial lymph flow, water accumulation, skin and subcutaneous tissue elasticity, and the possibility of using this information to diagnose lipedema. Methods and Results: Fifty patients with lipedema and 50 control subjects (women) were included. The Indocyanine Green (ICG) lymphography, LSC, skin water measurement, skin durometry, and deep tissue tonometry were done in all participants. ICG lymphography revealed: (1) Slower lymph flow in lipedema patients; after 3 minutes of feet movement in a horizontal position, the ICG-dyed lymph reached the upper calf level in 8% of lipedema patients compared with 56% in the control group (p ˂ 0.0001). (2) More than three LVs were noticed more often in lipedema patients. (3) The higher number of abnormal LV images at all limb levels and during each observation stage with a statistically significant number of foggy and dilated. (4) Statistically significant higher fluorescent intensity in all limb levels. Skin water concentration was higher in the feet in lipedema (p = 0.000189). Conclusion: Our studies have shown the differences in superficial lymph flow and water concentration between lipedema and normal limbs. Data proove the usefulness of ICG lymphography, skin water concentration and skin and subcutaneous tissue elasticity measurements in diagnosing lipedema.

The aim of the present case study was to report the 3-year follow-up of a male patient with lipedema and subclinical systemic lymphedema evaluated using multi-segment bioimpedance. The report describes the case of a 53-year-old male with a history of oncological surgery involving lymph node clearance in the right inguinal region followed by radiotherapy and chemotherapy. The physical examination revealed lipedema and lymphedema in the right lower limb. The patient was submitted to multi-segment bioimpedance, circumference measurements and volumetry, with the detection of clinical lymphedema of the limb. The patient underwent intensive treatment for lymphedema using the Godoy Method®, which resulted in a substantial reduction in the edema. However, at the 1-year follow-up, the patient had progressed to subclinical systemic lymphedema, followed a year later by clinical systemic lymphedema evaluated using multi-segment bioimpedance. Lipedema is less frequent in men compared to women, but the increase in weight is an aggravating factor in both sexes. This condition initially affects the lower limbs, progressing to subclinical systemic lymphedema, followed by clinical systemic lymphedema determined using multi-segment bioimpedance, demonstrating that edema in patients with lipedema may be systemic.

In early 2019, the Lipedema Foundation, in partnership with advisors from the Lipedema patient and research communities, launched the Lipedema Foundation Registry — an initial confidential survey to help understand the condition. After three years, we are ecstatic to share this Registry First Look report, providing perspective on the diverse experiences of people with Lipedema. We are tremendously thankful to those who contributed their time and insights, without which this report would not have been possible. This report includes data from the first 521 fully completed Registry surveys from people who believe they have Lipedema, out of 2,000 in-progress responses. These 521 people represent 14,556 years of lived experience with Lipedema, across dimensions including: • Diagnosis: This report focuses on the experiences of 521 people who either report having received a Lipedema diagnosis, or have symptoms sufficient for them to believe they have Lipedema. Data from non-Lipedema populations has been collected, but is not presented in this report. • Amount of time living with Lipedema: Participants include women with less than 10 years duration of the condition, though almost half of survey respondents had lived with Lipedema for more than 30 years at the time of participation. • Geography: Though only in English at this time, the Registry is multinational, with 21% of contributions from outside the US. Much captured here is consistent with existing academic literature and surveys. Findings include: • The Registry data is consistent with research showing the majority of patients first notice symptoms around the time of puberty; more specifically, the Registry data shows peak onset of symptoms between ages 12 and 14. • As widely reported by patients, this data shows long delays between onset and treatment. On average, women sought medical attention 17 years after first noticing symptoms, and received a diagnosis 10 years later. • Participants were able to identify Lipedema-like features in their bodies at frequencies consistent with the medical literature. They found Lipedema-like texture throughout their bodies, though most frequently in the arms and legs. • Both typical and flaring pain are common. Heaviness, bruising, and sensitivity to touch are also common and speak further to patients’ quality of life. After analyzing the data, the Lipedema Foundation team conducted two focus groups with patients to help understand and contextualize the findings. Their interpretations, insights and quotes appear throughout. Though this report is a great start, we hope it can be a tool to advance Lipedema awareness, understanding and care. Key next steps include: • Challenging healthcare professionals to recognize and understand Lipedema, and stop stigmatizing and dismissing patients when they seek care. • Informing scientific hypotheses and the research agenda. • Expanding and diversifying Registry participation, to ensure it represents the true diversity of the Lipedema patient population. Analysis of patient experience reminds us that Lipedema can present in many ways. This diversity asks us to take a closer look at typical descriptions of Lipedema, and this report should influence how we think about anatomical changes in Lipedema and progression of the disorder. These insights must be followed up with formal medical studies, but many hypotheses to be tested have been captured here in the patients’ own voices.

Since 1940, several commonly cited lipedema diagnostic criteria have been published, but no one criteria has been universally adopted by research or clinical communities. A consequence of this is that interpretation of the lipedema research is dependent on knowledge of the lipedema parameters used to recruit lipedema patients into research studies, as they may vary between studies. This table summarizes key areas of agreement and descrepancy between published works and encourages all authors to rigorously document the inclusion and exclusion criteria that serve as the foundation of their clinical studies.

Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Background and aims: Lipoedema is a little-known condition that is often misdiagnosed. Lipoedema presents with nodular to swollen areas that can lead to induration, nodular, uneven skin, as well as dimpling and skin flap formation, most commonly on the lower extremities, more rarely on the upper extremities The accumulation of adipose tissue results in characteristic symmetrical swelling of the extremities, ending above the ankles or wrists (cuff-sign). Primary pain phenomena include localized pain, tenderness, painful tightness, and pain on touch and pressure during activities. To get an insight in necessary self-management of pain and symptoms, a narrative review was conducted to identify requirement of self-management for coping with phenomena of pain in lipoedema and associated comorbidities. Methods: The narrative literature review includes international medical and guideline databases, as well as social media reports from affected persons. Analysis was performed using the content analysis method. Requirements of self-management, coping behaviour as well as individual case descriptions were searched. Results: 48 publications were identified. Guidelines and publications on guidelines accounted for a large proportion. Presentation of results outlines the range of requirements to manage pain with a bio-psycho-social pattern in the synthesis. Limiting spontaneous and pressure pain and secondary pain phenomena such as joint pain and mobility limitations are described. The prevention of chronification of pain in association with lipoedema has not yet been a direct aim in the therapeutic strategy. Conclusions: A knowledge gap regarding the incidence of pain syndrome and chronification shows major deficits of self-management strategies and implies further research needs.

In recent years, more attention is being paid to the hormonal aspect of lipoedema. There are suggestions that lipoedema patients may have particular imbalances or sensitivities with regard to oestrogens and/ or progesterone. This article examines the specifics of gluteofemoral fat storage during pregnancy: increased gluteofemoral storage with strong resistance to lipolysis. It then asks if hormonal dysregulation in lipoedema patients could result in a hormonal profile that mimics pregnancy. Such a profile may include high levels of oestrogens, progesterone, prolactin and relaxin, or any combination of the above. This pseudopregnancy hormonal profile would instruct the body to store gluteofemoral fat and strongly resist all attempts to mobilise it.

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.

High-quality three-dimensional (3D) microscopy allows detailed, unrestricted and non-destructive imaging of entire volumetric tissue specimens and can therefore increase the diagnostic accuracy of histopathological tissue analysis. However, commonly used IgG antibodies are oftentimes not applicable to 3D imaging, due to their relatively large size and consequently inadequate tissue penetration and penetration speed. The lack of suitable reagents for 3D histopathology can be overcome by an emerging class of single-domain antibodies, referred to as nanobodies (Nbs), which can facilitate rapid and superior 2D and 3D histological stainings. Here, we report the generation and experimental validation of Nbs directed against the human endothelial cell-selective adhesion molecule (hESAM), which enables spatial visualization of blood vascular networks in whole-mount 3D imaging. After analysis of Nb binding properties and quality, selected Nb clones were validated in 2D and 3D imaging approaches, demonstrating comparable staining qualities to commercially available hESAM antibodies in 2D, as well as rapid and complete staining of entire specimens in 3D. We propose that the presented hESAM-Nbs can serve as novel blood vessel markers in academic research and can potentially improve 3D histopathological diagnostics of entire human tissue specimens, leading to improved treatment and superior patient outcomes.

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.