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Lipedema is usually thought of as a dis-ease of women. Potentially diagnostic comparative data is needed between patients with lip-edema and those with lower limb lymphedema (LLL). Since there is no gold standard to diagnose lipedema, some promising modalities such as Tissue Dielectric Constant (TDC) need to be investigated among patients with lipedema and lymphedema. This study was completed with a total of 26 patients (14 lipedema, 12 LLL). Local tissue water was assessed with Moisture MeterD compact (DelfinTech, Kuopio, Finland) according to the TDC method at 300 MHz within a 2.5 mm tissue penetration depth via the following reference points: Thigh, calf (20 cm upper and lower point of knee level, respectively), and malleoli (5 cm upper point of medial malleolus). Patients with LLL showed significantly higher TDC values and interlimb TDC ratios in all affected points and unaffected malleolus points compared to patients with lipedema. No significant difference was achieved between genders with LLL in all reference points. The area under the curve (AUC) for thigh, calf, and malleolus reference points were found as 0.851 (95%CI .678-1.00), 0.801 (95% CI 0.612-0.989) and 0.786 (95%CI 0.596-0.976), respectively. Patients with LLL showed significantly higher TDC values compared to patients with lipedema, these differences should be carefully interpreted in patients with bilateral LLL and those with lipo-lymphedema.

Lipedema is a relatively common, unrecognized connective tissue disorder. It affects about 11% of women across the globe. In lipedema, there is symmetrical abnormal deposition of fat especially in the lower extremities. Lipedema can be accompanied with pain, spider veins and easy bruising. Lipedema is rare in men. The disease is progressive in nature. Trigger points for lipedema appear to be puberty, pregnancy and menopause. The disease affects various aspects of the connective tissues like lymphatics, veins, skin, ligaments and even joints as it progresses. Oestrogen and progesterone abnormalities seem to have a role in the progression of the condition. Lipedema also appears to have a genetic predisposition. Lipedema is classified into 4 stages depending on the degree and type of abnormal fat deposition. The severe form can be confused with Dercum’s disease. Depending on the site of deposition of abnormal fat, lipedema is also classified into 5 different types. Lipedema is often confused to be obesity or lymphedema and treated accordingly. Treatments are based on the stages and types of lipedema. Lipedema is extremely difficult to manage with diet, exercises and bariatric surgery alone. All treatments are focused around improving the quality of life, improving physical abilities and appearances.

Lipoedema is an overlooked and often misdiagnosed condition, which mainly affects women. This review summarises the present knowledge of the condition. It is characterised by bilateral and symmetrical accumulation of subcutaneous adipose tissue mainly in the legs. Patients with lipoedema often display tenderness to palpation or spontaneous pain in the adipose tissue. Lipoedema is diagnosed based on the medical history and clinical findings. Treatment includes conservative and surgical options with the aim of relieving symptoms and increasing mobility, but there is a paucity of randomised controlled trials.

OBJECTIVE: Does short-term use of pneumatic compression devices (PCD) and off-the-shelf compression alleviate symptoms and improve quality of life in women with lipedema and secondary lipolymphedema? METHODS: Prospective, randomized controlled, industry-sponsored, proof-in-principle study comparing PCD plus conservative care (PCD+CC) to CC alone (control). Adult females with bilateral lipedema and secondary lymphedema were randomized to PCD+CC or CC. Outcome measures were lower limb and truncal circumferential measurements, bioimpedance, and quality-of-life, symptom, and pain intensity questionnaires. RESULTS: Both groups experienced improvements in leg circumference and bioimpedance with more improvement in the PCD+CC group than the CC group. Pain scores of the SF-36 survey and numerical rating scales were improved in the PCD+CC group. Wong-Baker Faces scores showed trends toward improvement in both groups. CONCLUSIONS: This proof-in-principle study supports conservative management with graduated compression and with or without PCD for improvement in leg circumference, bioimpedance measurements, and pain in patients with lipedema.

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.

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.

INTRODUCTION: Lipedema is a poorly known condition. Diagnosis is based almost exclusively on clinical criteria, which may be subjective and not always reliable. This study aimed to investigate regional body composition (BC) by dual-energy X-ray absorptiometry (DXA) in patients with lipedema and healthy controls and to determine cut-off values of fat mass (FM) indices to provide an additional tool for the diagnosis and staging of this condition. METHODS: This study is a single-center case-control study performed at Lausanne University Hospital, Switzerland. Women with clinically diagnosed lipedema underwent regional BC assessment by DXA. The control group without clinical lipedema was matched for age and body mass index (BMI) at a ratio of 1:2 and underwent similar examination. Regional FM (legs, arms, legs and arms, trunk, android and gynoid FM) was measured in (kg) and divided by FM index (FMI) (kg/m2) and total FM (kg). The trunk/legs and android/gynoid ratios were calculated. For all indices of FM distribution showing a significant difference between cases and controls, we defined the receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), sensitivity, specificity, and Youden's index. Types and stages of lipedema were compared in terms of FM indices. Correlation analyses between all FM distribution indices and lipedema stages were performed. RESULTS: We included 222 women (74 with lipedema and 148 controls). Overall, the mean age was 41 years (standard deviation [SD] 11), and mean BMI was 30.9 kg/m2 (SD 7.6). A statistically significant difference was observed for all DXA-derived indices of FM distribution between groups, except for arm FM indices. The ROC curve analysis of leg FM/total FM, as a potential indicator of lipedema, resulted in an AUC of 0.90 (95% confidence interval 0.86-0.94). According to Youden's index, optimal cut-off value identifying lipedema was 0.384. Sensitivity and specificity were 0.95 and 0.73, respectively. We found no significant differences between lipedema types and stages in terms of FM indices, nor significant correlations between the latter and lipedema stages. DISCUSSION/CONCLUSION: BC assessment by DXA, and particularly calculation of the leg FM/total FM index, is a simple tool that may help clinicians rule out lipedema in doubtful cases.

Lipedema may be considered a model for healthy expandability of subcutaneous adipose tissue (SAT). This condition is characterized by the disproportional and symmetrical SAT accumulation in the lower-body parts and extremities, avoiding the abdominal area. There are no circulating biomarkers facilitating the diagnosis of lipedema. We tested the hypothesis that women living with lipedema present a distinct pattern of circulating parameters compared to age- and BMI-matched women. In 26 women (Age 48.3 ± 13.9 years, BMI 32.6 ± 5.8 kg/m2; lipedema group: n=13; control group: n=13), we assessed circulating parameters of glucose and lipid metabolism, inflammation, oxidative stress, sex hormones and a proteomics panel. We find that women with lipedema have better glucose metabolism regulation represented by lower HbA1c (5.55 ± 0.62%) compared to controls (6.73 ± 0.85%; p<0.001); and higher adiponectin levels (lipedema: 4.69 ± 1.99 mmol/l; control: 3.28 ± 1.00 mmol/l; p=0.038). Despite normal glycemic parameters, women with lipedema have significantly higher levels of total cholesterol (5.84 ± 0.70 mmol/L vs 4.55 ± 0.77 mmol/L in control; p<0.001), LDL-C (3.38 ± 0.68 mmol/L vs 2.38 ± 0.66 mmol/L in control; p=0.002), as well as higher circulating inflammation (top 6 based on p-values: TNFSF14, CASP8, EN-RAGE, EIF4EBP1, ADA, MCP-1) and oxidative stress markers (malondialdehyde, superoxide dismutase and catalase). Our findings suggest that the expected association between activation of inflammatory and oxidative stress pathways and impaired glucose metabolism are counterbalanced by protective factors in lipedema.

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.

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.

The Wound, Ostomy and Continence Nurses (WOCN) Society charged a task force with updating the venous leg ulcer (VLU) algorithm to include the addition of lymphedema with the new title of "Compression for Lower Extremity Venous Disease and Lymphedema (CLEVDAL)." As part of the process, the task force was charged to develop consensus-based statements to serve as clinical guidance related to CLEVDAL. The 3-member task force assisted by a moderator completed a scoping literature review to identify recommendations supported by research to qualify as evidence-based and to identify areas where guidance is needed to provide CLEVDAL. Based on the findings of the scoping review, the WOCN Society convened a panel of experts to develop consensus statements to direct care for those with lower extremity venous disease and lymphedema. These consensus statements underwent a second round of content validation with a different panel of clinicians with expertise in venous disease and lymphedema management. This article reports on the scoping review and subsequent evidence-based statements, along with the generation and validation of consensus-based statements to assist clinical decision-making in the CLEVDAL algorithm.

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.

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: 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.