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Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options.

Edema of the lower extremities is always associated with a pathological condition that should be treated, especially in patients with chronic wounds. Because the underlying causes of edema can vary greatly and sometimes be complex, clinical and, if necessary, various diagnostic tests should also be performed. Often, a suspected clinical diagnosis can already be made after clinical inspection with testing of Stemmer's and Godet's signs. Sonographic examination should then be performed as the next diagnostic test. Although measurement techniques such as water plethysmography are currently considered gold standard for volume measurements, they are very complex and prone to error, so that they are rarely used in clinical routine today. In summary, it is recommended to perform a clinical examination, if possible in combination with sonography, for edema diagnosis. Especially at the beginning of the decongestion phase, regular circumferential measurements should be performed and documented. This documentation is of high relevance for evaluation of therapeutic success.

EXECUTIVE SUMMARY Nuclear medicine is an essential tool in the delivery of high-quality medical care, going beyond simple anatomical imaging to the use of physiological processes for both imaging and therapy. Nuclear medicine techniques were applied to the lymphatic system as early as the 1950s by Sherman et al. (1), using 198Au colloid (a beta emitter) as a therapeutic agent for lymph node metastasis. In the late 1960s and early 1970s, the ready availability of technetium-99m (99mTc) allowed more widespread lymphatic imaging (lymphoscintigraphy) with 99mTc colloid. In 1976, Ege (2) studied lymphatic flow in 848 patients, suggesting lymphoscintigraphy could demonstrate variable lymphatic drainage patterns, therefore allowing more accurate radiation therapy fields. In recent years, advances in radiopharmaceuticals and imaging technology have allowed more accurate localization of lymph nodes during lymphoscintigraphy and the development of the sentinel lymph node (SLN) concept. One of the first mentions of SLN was made in 1960 by Gould and Philben (3). They described a specific location of a node that drained the parotid gland. This node, located at the junction of the anterior and posterior facial veins, was described as the node most likely to contain metastasis. It was recommended that this node be investigated first before carrying out complete node dissection (3). The SLN concept was further explored by Cabanas (4) in 1977 when lymphangiography with contrast was used to identify a specific location for lymphatic drainage from the penis. Similar to what was described by Gould and Philben, Cabanas (4) felt that this 1 specific lymph node (located at the superficial epigastric vein by Cabanas for penile carcinoma) could be defined as the SLN for all patients. Individual variations demonstrated in the lymphatic channels and the location of the sentinel node since the initial investigations have confirmed that mapping of lymphatic drainage needs to be carried out for each patient undergoing SLN sampling. SLN identification can be done with optical agents, such as isosulfan or methylene blue, as well as with radiotracers and fluorescent tracers. Localization of the SLN(s) with these techniques in individual patients has allowed a more focused investigation of nodal drainage from a primary tumor site, preventing the morbidity and mortality of complete node bed dissection in patients with no clinical evidence of tumor in the regional nodal basin (5). One difficulty with reviewing the literature describing lymphoscintigraphy is the variety of tracers in use around the world and throughout the history of lymphoscintigraphy. Smaller particles tend to move through the lymphatics more quickly. Some tracers are more likely to stop at the first node they encounter, while others are more likely to move through the lymphatic system more readily, demonstrating channels, node beds, and central lymphatic structures. The tracer used depends on the clinical indication (e.g., sentinel node scintigraphy, lymphedema, or lymphatic vessel integrity), as well as availability and local regulations. In the United States, there are only 2 tracers generally available for clinical use: 99mTc sulfur colloid and 99mTc tilmanocept. In addition, injection techniques, imaging protocols, and camera technology can vary substantially, making comparisons between studies challenging. A discussion of these technical differences is beyond the scope of this document. These appropriate use criteria (AUC) have been developed to describe the appropriate use of radiopharmaceuticals for lymphoscintigraphy in SLN mapping and lymphedema. It is hoped that through these recommendations, nuclear medicine lymphatic imaging techniques will be used to benefit patients in the most cost-effective manner. Representatives from the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the Society for Vascular Medicine (SVM), the Australia and New Zealand Society of Nuclear Medicine (ANZSNM), the American College of Radiology (ACR), the Society of Surgical Oncology (SSO), the European Association of Nuclear Medicine (EANM), the American Head and Neck Society (AHNS), the American Society of Clinical Oncology (ASCO), the American Society of Breast Surgeons (ASBrS), the American College of Nuclear Medicine (ACNM), and the American College of Surgeons (ACS) assembled as an autonomous workgroup to develop these AUC. This process was performed in accordance with the Protecting Access to Medicare Act of 2014 (6). This legislation requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering any advanced diagnostic imaging services. Such services are defined as diagnostic magnetic resonance imaging (MRI), computed tomography (CT), and nuclear medicine procedures, including positron emission tomography (PET) and others, as specified by the Secretary of Health and Human Services in consultation with physician specialty organizations and other stakeholders (3). Lymphoscintigraphy usually causes trivial radiation exposures for the patient, the surgeon, and the staff handling any specimens that may contain radioactivity. Local regulations that address the handling of radiopharmaceuticals and exposure of the public should always be followed. Radiation exposures are also trivial for pregnant patients and infants exposed to someone who has been injected with lymphoscintigraphic agents labeled with 99mTc. The amount of radiopharmaceutical transferred from the interstitium into the blood and from the blood to the milk is very low. However, when performing an SLN procedure for breast cancer, it seems prudent to recommend the interruption of direct breastfeeding for 24 hours after administration of the radiopharmaceutical. There is a potential for more fetal or infant exposure if the radioisotope dissociates from the radiopharmaceutical; however, exposures will remain very small and likely of no consequence. The rapid decay of 99mTc (6-hour half-life) also allows for rapid return of radiation exposures to background levels within a short time. More detailed information can be found in the document “Advisory Committee on Medical Uses of Isotopes (ACMUI) Sub-Committee on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials” (https://www.nrc.gov/docs/ML1803/ML18033B034.pdf).

Socio-economic position is a well-established driver of health status in the United Kingdom. However, less is known about the reverse relationship — the effect health conditions have on socio-economic position and social mobility. The purpose of this qualitative study was to explore individual experiences and perceptions of the relationship between ill-health and social mobility amongst people with long-term physical health conditions. Structured, in-depth interviews or focus group discussions were conducted with 37 people with long-term physical health conditions (including asthma, cancer, diabetes, heart disease, back pain, arthritis and lipoedema) between November 2019 and January 2020. Participants were asked about the impact of physical health on their career, education, and social life. Factors affecting their ability to cope with their condition were also explored. Participants reported their conditions had been a barrier to upward, and a facilitator of downward social mobility. Physical health conditions were commonly reported to have affected the participants’ educational attainment, choice of occupation, financial stability, and retirement age. Participants also described a lack of understanding from employers about their conditions, with some experiencing instances of discrimination. Factors that reduced the extent to which their condition affects social mobility included, a feeling of control over their condition, support from their employers and knowledge of the available support systems. Individual experience, psychological make-up, and early-life experience also mediated the impact. Participants described clear regional differences in terms of access to services. Advice and support services were often filled by charitable organisations. In conclusion, physical ill-health was reported to have a substantial downward impact on social mobility; by negatively impacting a person's education, choice of occupation and earning ability. Key changes that may enable people to better manage their condition and its impact on social mobility include, improved training of and support from employers and better and consistent access to multi-disciplinary support services from the health and social care system.

Lipedema is an adipofascial disorder that almost exclusively affects women. Lipedema leads to chronic pain, swelling, and other discomforts due to the bilateral and asymmetrical expansion of subcutaneous adipose tissue. Although various distinctive morphological characteristics, such as the hyperproliferation of fat cells, fibrosis, and inflammation, have been characterized in the progression of lipedema, the mechanisms underlying these changes have not yet been fully investigated. In addition, it is challenging to reduce the excessive fat in lipedema patients using conventional weight-loss techniques, such as lifestyle (diet and exercise) changes, bariatric surgery, and pharmacological interventions. Therefore, lipedema patients also go through additional psychosocial distress in the absence of permanent treatment. Research to understand the pathology of lipedema is still in its infancy, but promising markers derived from exosome, cytokine, lipidomic, and metabolomic profiling studies suggest a condition distinct from obesity and lymphedema. Although genetics seems to be a substantial cause of lipedema, due to the small number of patients involved in such studies, the extrapolation of data at a broader scale is challenging. With the current lack of etiology-guided treatments for lipedema, the discovery of new promising biomarkers could provide potential solutions to combat this complex disease. This review aims to address the morphological phenotype of lipedema fat, as well as its unclear pathophysiology, with a primary emphasis on excessive interstitial fluid, extracellular matrix remodeling, and lymphatic and vasculature dysfunction. The potential mechanisms, genetic implications, and proposed biomarkers for lipedema are further discussed in detail. Finally, we mention the challenges related to lipedema and emphasize the prospects of technological interventions to benefit the lipedema community in the future.

Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema.

BackgroundThere are both conservative and surgical treatment options for Lipohyperplasia dolorosa (LiDo). A procedure that has been established since 1997 is the surgical treatment through Lymphological Liposculpture according to Cornely™.AimAfter extensive suctioning of the extremities, an extensive subcutaneous wound cavity with a trabecular connective tissue scaffold remains. Nevertheless, surgery-related complications are rare. Postoperative management and administration of antibiotics and antithrombotics are reviewed. The therapies for complications are presented in detail.Materials and methodsRetrospectively, the frequencies of adverse events in 1400 LiDo surgeries in 2020 were evaluated. The mean age of the patients was 47.81 years (range 16–78 years). Symmetrically, 504 outer legs (outer half of the limb [BO]), 504 inner legs (inner half of the limb [BI]), and 392 arms [A] were surgically treated.ResultsRelevant adverse events rarely occurred: infections (1.79%), seromas (0.79%), erysipelas (0.28%), necrosis (0.14%) and deep vein thrombosis (0.07).DiscussionWe were able to reduce the rate of postoperative complications to 3.07% in the Lymphological Liposculpture™ regime for the surgical treatment of LiDo. In their meta-analysis on liposuction, Kanapathy et al. reported an overall incidence of major surgical complications of 3.35%. The overall incidence of minor surgical complications was 11.62%, with seroma (5.51%) being the most common minor complication [26]. Kruppa et al. report that the liposuction procedure including fat removal for esthetic reasons has a complication rate of 9.5%. Wound infections with 4.5% and the formation of erysipelas with 4% are clearly in the foreground [20].

The most relevant hallmarks of cellulite include a massive protrusion of superficial adipose tissue into the dermis, reduced expression of the extracellular glycoprotein fibulin-3, and an unusually high presence of MUSE cells in gluteofemoral white adipose tissue (gfWAT) that displays cellulite. Also typical for this condition is the hypertrophic nature of the underlying adipose tissue, the interaction of adipocytes with sweat glands, and dysfunctional lymph and blood circulation as well as a low-grade inflammation in the areas of gfWAT affected by cellulite. Here, we propose a new pathophysiology of cellulite, which connects this skin condition with selective accumulation of endogenous lipopolysaccharides (LPS) in gfWAT. The accumulation of LPS within a specific WAT depot has so far not been considered as a possible pathophysiological mechanism triggering localized WAT modifications, but may very well be involved in conditions such as cellulite and, secondary to that, lipedema.

Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10–6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.

BACKGROUND: The aim of this study was to define outcomes after total knee arthroplasty (TKA) in lymphoedema and lipoedema patients managed by a multidisciplinary team and daily compression bandaging. METHODS: A retrospective study was performed in a single centre. Between 2007 and 2018, 36 TKA procedures were performed on 28 consecutive patients with a diagnosis of lymphoedema and lipoedema. Oxford Knee Scores (OKS), EuroQol-5D (EQ-5D) scores, satisfaction scores, radiographs, and complications were obtained at the final follow-up. Patients were admitted to the hospital up to two weeks prior to surgery and remained on the ward for daily compression bandaging by the specialist lymphoedema team. RESULTS: Over the study period, 36 TKAs were performed on 28 patients (5 males, 23 females) with a mean age of 71 years (range 54-90). Of these, 30 TKAs were in patients with lymphoedema, five with lipoedema, and one with a dual diagnosis. Overall, 28 TKAs (21 patients) were available at the final follow-up with a mean follow-up time of 61 months (range 9-138). The mean BMI was 38.5 kg/m2. The mean pre-operative and post-operative Oxford Knee Score increased from 18 (range 2-38) to 29 (range 10-54); p < 0.001. EQ-5D score increased from 0.48 (range 0.15-0.80) to 0.74 (0.34-1.00) (p < 0.001). Mean post-operative satisfaction was 7.6/10 (range 2-10), with 89.3% TKAs satisfied. Complications were one (4%, 1/28) deep vein thrombosis, one superficial wound infection, one prosthetic joint infection, one stiff knee requiring manipulation, and one intra-operative femoral fracture. CONCLUSIONS: Lymphoedema and lipoedema should not be seen as barriers to TKA if adopting a multidisciplinary approach.

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1–3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact.

INTRODUCTION: The lower limbs are a common body site affected by chronic edema. Imaging examination of the lymphatic system is useful to diagnose lymphoedema, identify structural changes in individuals, and guide interventional strategies. In this study, we used a protocol combining indocyanine green (ICG) lymphography and ICG-guided manual lymphatic drainage (MLD) for the diagnostic assessment of lower limb lymphoedema. MATERIALS AND METHODS: Patients with lower limb lymphoedema were divided into three groups by their medical history: primary, secondary cancer-related, or secondary non-cancer-related. ICG lymphography was conducted in three phases: initial observation, MLD to accelerate ICG dye transit and reduce imaging time, and imaging data collection. Lymphatic drainage regions were recorded, and the MD Anderson Cancer Center ICG staging was applied. We collected routine lymphoedema assessment data, including limb volume and bioimpedance spectroscopy measurements. RESULTS: Three hundred and twenty-six lower limbs that underwent ICG lymphography were analyzed. Eight drainage regions were identified. The ipsilateral inguinal and popliteal were recognized as the original regions, and the remaining six regions were considered compensatory regions that occur only in lymphoedema. More than half of the secondary cancer-related lower limb lymphoedema (57.6%) continued to drain to the ipsilateral inguinal region. The incidence of drainage to the ipsilateral inguinal region was even higher for the primary (82.8%) and secondary non-cancer-related (87.1%) groups. Significant associations were observed between cancer-related lymphoedema and the presence of compensatory drainage regions. CONCLUSIONS: We proposed a prospective ICG lymphography protocol for the diagnostic assessment of lower limb lymphoedema in combination with MLD. Eight drainage regions were identified, including two original and six compensatory regions.

OBJECTIVES: To contribute to a more in-depth assessment of shape, volume, and asymmetry of the lower extremities in patients with lipedema or lymphedema utilizing volume information from MR imaging. METHODS: A deep learning (DL) pipeline was developed including (i) localization of anatomical landmarks (femoral heads, symphysis, knees, ankles) and (ii) quality-assured tissue segmentation to enable standardized quantification of subcutaneous (SCT) and subfascial tissue (SFT) volumes. The retrospectively derived dataset for method development consisted of 45 patients (42 female, 44.2 ± 14.8 years) who underwent clinical 3D DIXON MR-lymphangiography examinations of the lower extremities. Five-fold cross-validated training was performed on 16,573 axial slices from 40 patients and testing on 2187 axial slices from 5 patients. For landmark detection, two EfficientNet-B1 convolutional neural networks (CNNs) were applied in an ensemble. One determines the relative foot-head position of each axial slice with respect to the landmarks by regression, the other identifies all landmarks in coronal reconstructed slices using keypoint detection. After landmark detection, segmentation of SCT and SFT was performed on axial slices employing a U-Net architecture with EfficientNet-B1 as encoder. Finally, the determined landmarks were used for standardized analysis and visualization of tissue volume, distribution, and symmetry, independent of leg length, slice thickness, and patient position. RESULTS: Excellent test results were observed for landmark detection (z-deviation = 4.5 ± 3.1 mm) and segmentation (Dice score: SCT = 0.989 ± 0.004, SFT = 0.994 ± 0.002). CONCLUSIONS: The proposed DL pipeline allows for standardized analysis of tissue volume and distribution and may assist in diagnosis of lipedema and lymphedema or monitoring of conservative and surgical treatments. KEY POINTS: • Efficient use of volume information that MRI inherently provides can be extracted automatically by deep learning and enables in-depth assessment of tissue volumes in lipedema and lymphedema. • The deep learning pipeline consisting of body part regression, keypoint detection, and quality-assured tissue segmentation provides detailed information about the volume, distribution, and asymmetry of lower extremity tissues, independent of leg length, slice thickness, and patient position.

PURPOSE: Lipoedema is a progressive adipose (fat) disorder, and little is known about its psychological effect. This study aimed to determine the experiences of physical and mental health and health care across stages of lipoedema. METHODS: Cross-sectional, secondary data from an anonymous survey (conducted 2014-2015) in Dutch and English in those with self-reported lipoedema were used (N = 1,362, Mdnage = 41-50 years old, 80.2% diagnosed). χ2 analyses of categorical data assessed lipoedema stage groups 'Stage 1-2' (N = 423), 'Stages 3-4' (N = 474) and 'Stage Unknown' (N = 406) experiences of health (physical and psychological), and health care. RESULTS: Compared to 'Stage 1-2', 'Stage 3-4' reported more loss of mobility (p =  < .001), pain (p =  < .001), fatigue (p = .002), problems at work (p =  < .001) and were seeking treatment to improve physical functioning (p =  < .001) more frequently. 'Stage 3-4' were more likely to report their GP did not have knowledge of lipoedema, did not take them seriously, gave them diet and lifestyle advice, dismissed lipoedema, and treated them 'badly' due to overweight/lipoedema compared to 'Stage 1-2' (p =  < .001). 'Stage 3-4' were more likely to report depression (p =  < .001), emotional lability (p = .033) eating disorders (p = .018) and feeling lonelier, more fearful, and stayed at home more (p =  < .001) and less likely to have visited a psychologist (p =  < .001) compared to 'Stage 1-2'. CONCLUSIONS: A divergent pattern of physical and psychological experiences between lipoedema stages reflects physical symptom differences and differences in psychological symptoms and health care experiences. These findings increase the understanding of lipoedema symptoms to inform psychological supports for women with lipoedema in navigating chronic health care management.

Background: Lipedema is a distinct adipose disorder from obesity necessitating awareness as well as different management approaches to address pain and optimize quality of life (QoL). The purpose of this proof-of-principle study is to evaluate the therapeutic potential of physical therapy interventions in women with lipedema. Methods and Results: Participants with Stage 1-2 lipedema and early Stage 0-1 lymphedema (n = 5, age = 38.4 ± 13.4 years, body mass index = 27.2 ± 4.3 kg/m2) underwent nine visits of physical therapy in 6 weeks for management of symptoms impacting functional mobility and QoL. Pre- and post-therapy, participants were scanned with 3 Tesla sodium and water magnetic resonance imaging (MRI), underwent biophysical measurements, and completed questionnaires measuring function and QoL (patient-specific functional scale, PSFS, and RAND-36). Pain was measured at each visit using the 0-10 visual analog scale (VAS). Treatment effect was calculated for all study variables. The primary symptomatology measures of pain and function revealed clinically significant post-treatment improvements and large treatment effects (Cohen's d for pain VAS = -2.5 and PSFS = 4.4). The primary sodium MRI measures, leg skin sodium, and subcutaneous adipose tissue (SAT) sodium, reduced following treatment and revealed large treatment effects (Cohen's d for skin sodium = -1.2 and SAT sodium = -0.9). Conclusions: This proof-of-principle study provides support that persons with lipedema can benefit from physical therapy to manage characteristic symptoms of leg pain and improve QoL. Objective MRI measurement of reduced tissue sodium in the skin and SAT regions indicates reduced inflammation in the treated limbs. Further research is warranted to optimize the conservative therapy approach in lipedema, a condition for which curative and disease-modifying treatments are unavailable.

Background: Edema is highly prevalent in patients with cardiovascular disease and is associated with various underlying pathologic conditions, making it challenging for physicians to diagnose and manage. Methods: We report on presentations from a virtual symposium at the Annual Meeting of the European Venous Forum (25 June 2021), which examined edema classification within clinical practice, provided guidance on making differential diagnoses and reviewed evidence for the use of the treatment combination of Ruscus extract, hesperidin methyl chalcone and vitamin C. Results: The understanding of the pathophysiologic mechanisms underlying fluid build-up in chronic venous disease (CVD) is limited. Despite amendments to the classic Starling Principle, discrepancies exist between the theories proposed and real-world evidence. Given the varied disease presentations seen in edema patients, thorough clinical examinations are recommended in order to make a differential diagnosis. The recent CEAP classification update states that edema should be considered a sign of CVD. The combination of Ruscus extract, hesperidin methyl chalcone and vitamin C improves venous tone and lymph contractility and reduces macromolecule permeability and inflammation. Conclusions: Data from randomized controlled trials support guideline recommendations for the use of Ruscus extract, hesperidin methyl chalcone and vitamin C to relieve major CVD-related symptoms and edema.

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.