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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.

OBJECTIVE: Advanced pneumatic compression devices (APCDs) have been shown to be an effective intervention for lymphedema when used as part of a self-care maintenance treatment regimen. However, adherence to self-care is poor, and APCDs require patients to be immobile during treatment. We sought to evaluate the safety and efficacy of a novel non-pneumatic compression device (NPCD) for treating lymphedema versus an APCD. METHODS: A randomized, crossover head-to-head investigation at five US sites in 2021. Patients were randomized to either the NPCD or a commercially-available APCD. Subjects used the randomly assigned initial device for 28 days with a 4-week washout period prior to a comparable 28-day utilization of the second device. RESULTS: Data from 50 adult women with unilateral breast cancer-related lymphedema (BCRL) were analyzed. When compared with the APCD, the NPCD was associated with greater mean reduction in limb edema volume (64.6% vs. 27.7%, p<0.001), significantly greater mean improvements in quality of life scores, greater adherence (95.6% vs. 49.8%, p<0.001), and greater satisfaction with the device (90% vs. 14%, p<0.001). Patients indicated that the NPCD facilitated exercise and was convenient for travel. No adverse events were reported. CONCLUSIONS: The novel NPCD is an effective maintenance treatment for reducing limb volume in BCRL patients. The device was more effective than an APCD and resulted in higher adherence to self-care interventions and greater patient satisfaction.

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.

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.

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.

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.

Lower extremity edema is a common complaint of patients across all medical specialties. This is a wide group of conditions, ranging from relatively minor conditions such as false swelling in lipedema to life-threatening conditions such as heart failure and nephrotic syndrome. The most common cause of chronic edema is chronic venous disease. High-quality differential diagnosis aims to determine the etiology of edema and initiate targeted treatment.

The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.

OBJECTIVE: Upper extremity lymphedema (UEL) is a burdensome disease with significant impact on quality of life underscoring the importance of quality of life measurements in this patient population. Only recently, the LYMPH Q Upper Extremity Module, a new patient-reported outcome measurement (PROM), has been developed. The aim of the study was to translate the LYMPH Q Upper Extremity Module from English to German and perform a comprehensive validation. METHODS: Translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines. To validate the German LYMPH Q, a multicenter study was conducted. Internal consistency was determined by Cronbach's alpha. Reliability was assessed by the intra-class correlation coefficient (ICC). To analyse construct validity, a Pearson correlation coefficient between the LYMPH Q, quickDASH and SF-36 was calculated. Responsiveness was assessed by comparing the pre- and postoperative LYMPH Q scores in five patients receiving lymphatic reconstructive surgery. RESULTS: Validation was performed in a cohort of 65 patients. Internal consistency of the different domains was good to excellent (α: 0.87-0.97). ICC ranged from 0.74 to 0.92. The domains of the LYMPH Q correlated significantly with the corresponding domains of the SF-36 and quick DASH. Construct validity was good with eight of ten hypotheses confirmed. Significant improvements of function (46.4 ± 13.3 vs. 77.8 ± 11.5; p= 0.03), symptoms (42.0 ± 10.7 vs. 70.6 ± 11.6; p= 0.02) and psychological well-being (40.4 ± 14.6 vs. 78.0 ± 17.3; p= 0.03) were observed after lymphatic reconstructive surgery. CONCLUSION: The German version of The LYMPH Q Upper Extremity Module is conceptually equivalent to the original English version. It is a reliable and valid PROM to assess physical and psychological impairments in patients with UEL.

BACKGROUND: Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited to five peer-reviewed publications. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. Considering the chronically progressive nature of lipedema, it was hypothesized that younger patients with lower body mass index and stage would report better results. METHODS: This retrospective, single-center, noncomparative study included lipedema patients who underwent liposuction between July of 2009 and July of 2019. After a minimum of 6 months since the last surgery, all patients completed a disease-related questionnaire. The primary endpoint was the need for complex decongestive therapy based on a composite score. Secondary endpoints were the severity of complaints (i.e., spontaneous pain, sensitivity to pressure, feeling of tension, bruising, impairment of body image) measured on a visual analogue scale. RESULTS: One hundred six patients underwent a total of 298 large-volume liposuctions (mean lipoaspirate, 6355 ± 2797 ml). After a median follow-up of 20 months (interquartile range, 10 to 42 months), a median complex decongestive therapy score reduction of 37.5 percent (interquartile range, 0 to 88.8 percent; p < 0.0001) was observed. An improvement in lipedema-associated symptoms was also observed (p < 0.0001). The percentage reduction in complex decongestive therapy scores was greater in patients with a body mass index less than or equal to 35 kg/m2; (compared to higher body mass index; p < 0.0001) and in stage I and II patients (compared to stage III patients; p = 0.0019). CONCLUSION: Liposuction reduces the severity of symptoms and the need for conservative treatment in lipedema patients, especially if it is performed in patients with a body mass index below 35 kg/m2; at an early stage of the disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

In daily practice, medical history and physical examination are commonly coupled with anthropometric measurements for the diagnosis and management of patients with lymphatic diseases. Herein, considering the current progress of ultrasound imaging in accurately assessing the superficial soft tissues of the human body; it is noteworthy that ultrasound examination has the potential to augment the diagnostic process. In this sense/report, briefly revisiting the most common clinical maneuvers described in the pertinent literature, the authors try to match them with possible (static and dynamic) sonographic assessment techniques to exemplify/propose an 'ultrasound-guided' physical examination for different tissues in the evaluation of lymphedema.