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OBJECTIVES: The association between serum Vitamin D (Vit. D) and mood disorders in lipedema patients has not been investigated. Therefore, the main aim of this study is to investigate the correlation between serum Vit. D, depression and anxiety risk. METHODS: A cross-sectional cohort of lipedema patients were investigated by collecting the clinical and demographic data. The Hamilton Depression Scale (HAM-D) and the Hamilton of Anxiety Scale (HAM-A) were used to evaluating the risk of depression and anxiety. Serum concentrations of Vit. D were measured. The association between Vit. D levels and both HAM-A and HAM-D scores were statistically examined by bivariate and partial correlations. RESULTS: Forty lipedema patients were enrolled in this study. Around two-thirds of them had a higher depression or anxiety risk, and 77.5% were under the normal serum Vit. D levels. A significant and inverse correlation was observed between serum Vit. D levels and both HAM-D (r=-0.661, p<0.001), and HAM-A (r=-0.496, p=0.001) scores. This strong association was sustained after the statistical model adjusted for the main potential confounding factors (age, body mass index (BMI), disease duration, and lipedema stages). Additionally, serum Vit. D correlated significantly and inversely with BMI (r=-0.647, p<0.001). Moreover, BMI significantly correlated with HAM-D: r=0.560, p<0.001, and HAM-A: r=0.511, p=0.00. CONCLUSIONS: This study suggests a strong correlation between Vit. D levels, depression scores, and anxiety scores in lipedema patients. Our results also demonstrate a strong and direct relationship between BMI, Vit. D levels, depression, and anxiety.

Lipedema is a chronic feminine disease that causes abnormal fat deposition in lower limbs and occasionally upper limbs. Easy bruising and pain are common. Lipedema patients suffer from both physical and psychological disability. Despite the relatively high prevalence and the impact on the quality of life, little is known about the disease. The majority of patients are misdiagnosed as lymphedema or obesity. The objective was to perform a non-systematic review on lipedema literature, related to diagnosis and therapy. Regarding pathophysiology, alterations are not exclusively confined to adipose tissue. Lymphatic dysfunction, cardiovascular variations, blood capillary fragility and increased permeability are common. Patients often present with neurological alterations and hormonal malfunction. Elevated cutaneous sodium has been documented. Due to the absence of a defined etiology, evidence-based research is difficult in the management of lipedema. The setting of realistic expectations is important for both patient and medical care provider. The major aims of the management are multimodal for improvements in the quality of life; reduction in heaviness and pain, reshaping the affected limbs, weight control, improvements in mobility. Compression garments, physical therapy, exercise regimens, diet and psychological counseling are necessities. For selected patients, surgical treatment is an added option.

BACKGROUND: Lipedema is characterized by the deposition of abnormal fat in the lower and upper limbs bilaterally. It is a disease with high prevalence and genetic characteristics. Non-specific and non-quantified increases in the thickness of the subcutaneous tissue have previously been demonstrated using magnetic resonance imaging and computed tomography. OBJECTIVES: To evaluate the thickness of the dermis and subcutaneous tissue in predetermined areas as a distinguishing feature between individuals with and without lipedema using ultrasound. METHODS: Ultrasound images of 89 female patients were analyzed, including patients undergoing clinical investigation for venous insufficiency or lipedema who underwent ultrasound evaluations at our institution. Patients were divided in two groups: with lipedema clinically diagnosed and those without lipedema. They underwent a common Doppler protocol for venous mapping to assess venous insufficiency associated with the evaluation of dermis and subcutaneous thickness at pre-defined points of the lower limbs. RESULTS: There were 63 patients with lipedema. Anterior thigh, pre-tibial and lateral aspect of the leg and supra-just medial malleolar region were significantly different. Supra-just medial malleolar region was significantly different with BMI above 25. An optimal cutoff value was calculated for the ultrasound diagnosis of lipedema using thickness of the dermis and subcutaneous tissues. CONCLUSIONS: Studied criteria allow use of simple and reproducible ultrasound cutoff values to diagnose lipedema in the lower limbs. Pre-tibial region thickness measurement, followed by thigh and lateral leg thickness are recommended for the ultrasound diagnosis of lipedema.

AIM: Fluid and macromolecule transport from the interstitium into and through lymphatic vessels is necessary for tissue homeostasis. While lymphatic capillary structure suggests that passive, paracellular transport would be the predominant route of macromolecule entry, active caveolae-mediated transcellular transport has been identified in lymphatic endothelial cells (LECs) in vitro. Caveolae also mediate a wide array of endothelial cell processes, including nitric oxide regulation. Thus, how does the lack of caveolae impact "lymphatic function"? METHODS: Various aspects of lymphatic transport were measured in mice constitutively lacking caveolin-1 ("CavKO"), the protein required for caveolae formation in endothelial cells, and in mice with a LEC-specific Cav1 gene deletion (Lyve1-Cre x Cav1flox/flox ; "LyCav") and ex vivo in their vessels and cells. RESULTS: In each model, lymphatic architecture was largely unchanged. The lymphatic conductance, or initial tissue uptake, was significantly higher in both CavKO mice and LyCav mice by quantitative microlymphangiography and the permeability to 70 kDa dextran was significantly increased in monolayers of LECs isolated from CavKO mice. Conversely, transport within the lymphatic system to the sentinel node was significantly reduced in anaesthetized CavKO and LyCav mice. Isolated, cannulated collecting vessel studies identified significantly reduced phasic contractility when lymphatic endothelium lacks caveolae. Inhibition of nitric oxide synthase was able to partially restore ex vivo vessel contractility. CONCLUSION: Macromolecule transport across lymphatics is increased with loss of caveolae, yet phasic contractility reduced, resulting in reduced overall lymphatic transport function. These studies identify lymphatic caveolar biology as a key regulator of active lymphatic transport functions.

BACKGROUND: When performing large volume liposuction, perioperative management of lipedema patients with coagulation disorders remains challenging due to a lack of clinical experience. With a prevalence of 1% of von Willebrand disease (VWD) in the general population, basic knowledge on diagnostic and adapted surgical strategies are essential for patients' safety. OBJECTIVE: Based on a selective literature review, the purpose of this article is to present a standardized algorithm for diagnosis and perioperative treatment of VWD patients undergoing large volume liposuction. METHODS: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term "(((liposuction) OR (surgery)) OR (lipectomy)) AND (((VWD) OR (hemostaseology)) OR (von Willebrand disease))". Included were articles published in English or German until November 2020. RESULTS: The evidence for large volume liposuctions in patients with VWD is limited. Experience is largely based on operations with similar bleeding risks. A safe performance requires an adjustment of the surgical technique and a customized perioperative drug substitution plan. According to the current literature, perioperative thromboembolic events appear to be rare with adequate drug treatment. CONCLUSION: The implementation of the developed diagnostic and treatment algorithm may help further reducing bleeding complications and improve the safety for treated patients.

Lipedema is an infrequently recognized disorder. It is characterized by bilateral painful enlargement of the legs due to abnormal depositions of subcutaneous fat, that can result in considerable disability. The diagnosis is established on the basis of medical history and clinical findings. Early diagnosis of this disorder is necessary to start adapted management and prevent progression and complications of the disease. Currently there is no curative treatment. The conservative treatment requires a multidimensional approach including manual lymph drainage, compression garments and management or prevention of obesity as well as other comorbidities. In some cases, surgery may be considered.

Lipedema is a widespread in concern of etiology partially unknown disease especially in women. In many cases it is accompanied by bleeding complications. Our current work focuses on possible coagulation disorders as potential sources of such bleeding complications. Since only a minority of our patients showed a coagulation defect it is suggestive that the main underlying reason for bleeding in lipedema is of cutaneous origin what may only be forwarded by simultaneously existing coagulation disorders.

PURPOSE OF REVIEW: Williams syndrome is a multisystem disorder caused by a microdeletion on chromosome 7q. Throughout infancy, childhood, and adulthood, abnormalities in body composition and in multiple endocrine axes may arise for individuals with Williams syndrome. This review describes the current literature regarding growth, body composition, and endocrine issues in Williams syndrome with recommendations for surveillance and management by the endocrinologist, geneticist, or primary care physician. RECENT FINDINGS: In addition to known abnormalities in stature, calcium metabolism, and thyroid function, individuals with Williams syndrome are increasingly recognized to have low bone mineral density, increased body fat, and decreased muscle mass. Furthermore, recent literature identifies a high prevalence of diabetes and obesity starting in adolescence, and, less commonly, a lipedema phenotype in both male and female individuals. Understanding of the mechanisms by which haploinsufficiency of genes in the Williams syndrome-deleted region contributes to the multisystem phenotype of Williams syndrome continues to evolve. SUMMARY: Multiple abnormalities in growth, body composition, and endocrine axes may manifest in individuals with Williams syndrome. Individuals with Williams syndrome should have routine surveillance for these issues in either the primary care setting or by an endocrinologist or geneticist.

Background: Lack of diagnostic awareness of lipedema and frequent confusion with obesity or lymphedema may be an obstacle for treatment. The clinical effects of conservative treatment methods are not clearly known. This study investigated the effects of exercise-based rehabilitation combined with complete decongestive therapy (CDT) or intermittent pneumatic compression therapy (IPCT) or alone in patients with severe lipedema. Methods: Thirty-three women with severe (type 3, stage III or IV) lipedema diagnosed according to the revised-Wold criteria were randomized into three groups: Group 1 (CDT plus exercises), Group 2 (IPCT plus exercises), and Group 3 (control-exercises alone). All groups received 30 sessions of combined (aerobic, strengthening, and stretching) exercise program. In addition, there were CDT in Group 1 and IPCT in Group 2 five times a week for 6 weeks. The primary outcome measure was the limb volume measurements. The secondary outcome measures were anthropometric measurements (body weight, body mass index, waist-to-height ratio, waist-to-hip ratio), 6-minute walk test, visual analog scale for pain, fatigue severity scale, Beck Depression Inventory, and Short Form Health Survey-36 (SF-36). Results: Thirty-one participants completed the interventions. Limb volumes (p = 0.017, ηp2 = 0.562 for right; p < 0.001, ηp2 = 0.775 for left), pain (p = 0.045, ηp2 = 0.199), and physical functioning subscore of SF-36 (p = 0.040, ηp2 = 0.465) differed significantly between treatments originating from Group 1. Conclusions: All programs improved outcome measurements after the intervention. However, when the difference between treatments was investigated, CDT administered in addition to the exercises has been shown to provide significant improvements in reducing limb volumes, pain, and physical function. Clinical trial registration number: The study was registered at the US National Institutes of Health (ClinicalTrials.gov) (NCT03924999) and available at https://clinicaltrials.gov/ct2/show/NCT03924999?term=lipedema&draw=2&rank=6.

Background: The aim of this study is to investigate the effect of complex decongestive physiotherapy (CDP) plus intermittent pneumatic compression (IPC) applications on lower extremity limb circumference and volume in patients with lipedema. Methods and Results: In measurement of limb volume and circumference measurement, the Perometer 400 NT was used before and after treatment. The perometer measurements in this study were performed in the certain five reference points (cB, cC, cD, cE, and CF). All participants included in the study were included in a treatment protocol consisting of CDP and IPC. It was seen that statistically significant reduction was found in the circumference of 3 of the 5 points of measurements performed in the left limb, whereas statistically significant reduction was found in the circumference of 4 of the 5 points of measurements performed in the right limb. When the assessments of limb volume performed with the perometer were compared before and after CDP, it was seen that statistically significant reduction was found in the volume of both limbs. Conclusion: This reduction indicates that CDP is effective in the treatment of lower extremity lipedema. Clinicaltrials.gov with an ID of NCT04492046.

Many drugs are responsible, through different mechanisms, for peripheral edema. Severity is highly variable ranging from slight edema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often non-inflammatory and bilateral, some drugs are associated with peripheral edema that is readily erythematous (e.g., pemetrexed) or unilateral (e.g., sirolimus). Thus, drug-induced peripheral edema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory edema), sodium/water retention (renal edema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability edema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of drug.

Significance: Primary lymphedema is a chronic condition without a cure. The lower extremities are more commonly affected than the arms or genitalia. The disease can be syndromic. Morbidity includes decreased self-esteem, infections, and reduced function of the area. Recent Advances: Several mutations can cause lymphedema, and new variants continue to be elucidated. A critical determinant that predicts the natural history and morbidity of lymphedema is the patient's body mass index (BMI). Individuals who maintain an active lifestyle with a normal BMI generally have less severe disease compared to subjects who are obese. Because other causes of lower extremity enlargement can be confused with lymphedema, definitive diagnosis requires lymphoscintigraphy. Critical Issues: Most patients with primary lymphedema are satisfactorily managed with compression regimens, exercise, and maintenance of a normal body weight. Suction-assisted lipectomy is our preferred operative intervention for symptomatic patients who have failed conservative therapy. Suction-assisted lipectomy effectively removes excess subcutaneous fibro-adipose tissue and can improve underlying lymphatic function. Future Directions: Many patients with primary lymphedema do not have an identifiable mutation and thus novel variants will be identified. The mechanisms by which mutations cause lymphedema continue to be studied. In the future, drug therapy for the disease may be developed.

The aim of the case report was to discuss generalised oedema in a patient with lipoedema and obesity, describing a novel concept of a stage 0 lymphoedema that we denominated as subclinical systemic lymphoedema. A 35-year-old female patient reported to our clinic due to telangiectasia of the lower limbs and leg pain that increased in the heat and when she spend a lot of time in a standing position. The patient had a physical appearance of lipoedema involving the upper and lower limbs associated with a family history o