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Methemoglobinemia is characterized by an increased level of methemoglobin (MetHb) in the peripheral blood. MetHb levels increase after tumescent anesthesia and need to be monitored. If a patient becomes symptomatic and/or the MetHb levels increase >10%, intravenous injection of an antidote is recommended. Toluidine blue is twice as effective as methylene blue in this respect.A 27-year-old woman with advanced lipedema underwent her third liposuction under tumescent anesthesia. After surgery, her MetHb levels increased and needed injection of toluidine blue. She developed an acute and painful edema after extravasation of some toluidine blue due to a bursting vein. This is the first report in the recent medical literature. Clinical presentation, course, and treatment are described.

Background and Aim: Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods: Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results: Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p < 0.005) and Obese (p < 0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p < 0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p < 0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion: Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.

Advanced lymphedema is associated with a number of adverse skin changes including color, thickening of the epidermis, dryness, and hyperkeratosis. These changes are related to prolonged lymph stasis and contribute to an increased risk of infection. Similarly, lipedema is associated with skin thickening and appearance of nodular adipose deposition. Skin care is essential in both conditions. We examined whether inclusion of targeted skin products for 2 weeks to an established pre-surgical conservative treatment program was associated with beneficial effects on the skin condition in 150 patients with lymphedema and lipedema. Patients were randomly assigned to control or one of two treatment groups. All three groups (and for both lymphedema and lipedema) demonstrated a significant reduction in softness. Dimpling/ redness was significantly reduced in the targeted skin product groups for both patients with lymphedema or lipedema. Only patients with lipedema demonstrated a significant reduction in dryness/ hyperkeratosis following targeted skin product treatment. This study demonstrates that short-term use of targeted skin products in both patients with lymphedema and lipedema can be of benefit and further studies are needed to replicate these results and explore possible mechanisms.

Lipedema is a chronic fat disorder with disproportional fat distribution, especially around the legs, hips, and sometimes arms, and it affects women almost exclusively. The major symptoms and complaints include pain in the soft tissue and the feeling of “heavy legs.” The perception of pain depends to a high degree on the psychological condition of the patient. Obesity is the major comorbidity and can worsen lipedema. In combination with impaired levels of physical activity, there is an increase in interstitial filtration, and noninfectious inflammation with capillary leakage can occur. Eventually, chronic edema develops due to the dynamic insufficiency of the lymphatic system. However, edema is not a pathognomonic aspect of lipedema. There are many controversies and myths about the condition lipedema, and no objective diagnostic tool is available to confirm the diagnosis. Therapeutic approaches in lipedema are multimodal and focus on the biomedical, psychological, and functional aspects involved with the disorder. A lifestyle change is often part of the therapeutic program, along with other therapeutic interventions, such as exercise, compression, weight management, and nutritional and psychological support. Clinimetrics with validated techniques in all fields of human functioning of a lipedema patient are mandatory to objectively evaluate the improvements that are due to the treatment program. Liposuction is a technique to remove fat and is therefore introduced to treat lipedema. Some doctors who offer the procedure state that “liposuction leads to comprehensive and long-term improvements in lipedema and cures the disease.” These statements are often too optimistic and lead to high costs for the patient and disappointment in the end. However, liposuction can lead to improvements in lipedema when offered within a therapeutic program that includes other nonoperative modalities for the correct selection of patients according to their medical criteria. It cannot be emphasized enough that liposuction is not a method that should be used to treat obesity.

Subcutaneous adipose tissue diseases involving adipose tissue and its fascia, also known as adipofascial disorders, represent variations in the spectrum of obesity. The adipofascia diseases discussed in this chapter can be localized or generalized and include a common disorder primarily affecting women, lipedema, and four rare diseases, familial multiple lipomatosis, angiolipomatosis, Dercum disease, and multiple symmetric lipomatosis. The fat in adipofascial disorders is difficult to lose by standard weight loss approaches, including lifestyle (diet, exercise), pharmacologic therapy, and even bariatric surgery, due in part to tissue fibrosis. In the management of obesity, healthcare providers should be aware of this difficulty and be able to provide appropriate counseling and care of these conditions. Endocrinologists and primary care providers alike will encounter these conditions and should consider their occurrence during workup for bariatric surgery or hypothyroidism (lipedema) and in those that manifest, or are referred for, dyslipidemia or diabetes (Dercum disease). People with angiolipomas should be worked up for Cowden’s disease where a mutation in the gene PTEN increases their risk for thyroid and breast cancer. This chapter provides details on the pathophysiology, prevalence, genetics and treatments for these adipofascial disorders along with recommendations for the care of people with these diseases. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Obesity is a clinical condition that affects millions of people around the world and is associated with inflammatory processes. The aim of the present study was to report the association between obesity, lipedema, and systemic fluid retention, characterizing subclinical systemic lymphedema with aggravating factors. A 50-year-old female patient weighing 150 kilograms (body mass index: 60.2 kg/m2) reported being obese since childhood, but more located on the hips. She had a family history of this body configuration. Electrical bioimpedance analysis revealed generalized edema, constituting systemic lymphedema. Subclinical systemic lymphedema is caused by obesity and lipedema is also associated with this condition.

The V.A.C.-Prevena™ dressing (Prevena Incision Dressing) is suitable for the treatment of surgical high-risk wounds (closed surgical incision management). It leads to the reduction of wound in­ fections and to improvement of wound healing in patients with relevant secondary diagnoses (e. g. diabetes mellitus, obesity, nicotine abuse, vascular problems, etc.). This dressing is placed directly on surgical sutures and a vacuum device is used to create suction. This results in a reduction of possible complications in wound healing (wound infections, wound dehiscence, haematomas, seromas, oedema. The dressing can be left in place for several days. We were interested to find out whether a circular bandage, which is not only applied directly to the wound site but also to the wider wound environment, is more effective and whether there are new indications for this.

Cellulite is a change of the skin and subcutaneous tissue that develops mainly in the thighs and gluteal region of almost all women. Many concepts in the pathological physiology of cellulite are to some extent contradictory and inconclusive; however, some studies point to structural changes in the dermis and subcutaneous tissue. A correlation of cellulite with focal hypertrophic subcutaneous connective tissue strands and lower density of connective tissue septa in subcutaneous tissue also point to changes in the related gluteal fascia and thus in the closely interlaced gluteal muscles. A rapid degenerative development of the muscle dynamics that were originally gained over generations unquestionably occurs in the Caucasian race and its related urbanization. The gender-specific dimorphism in the subcutaneous area must also be investigated further, since almost exclusively women are affected. For this reason we have anatomically examined male and female gluteal zones and demonstrated significant genderspecific changes. In particular, a weakening of the muscle-tendon and muscle-fascia dynamics of the gluteal muscles appears to be responsible for the round, superficially visible dermal changes. The entire embryonic unit of the muscle-fascia-skin structures in the buttocks and thigh area is involved in female cellulite. A transformation of these degenerative changes through regenerativemeasures, such as active movement and shock wave therapy is, therefore, appropriate and necessary.

Cellulite is a change of the skin and subcutaneous tissue that develops mainly in the thighs and gluteal region of almost all women. Many concepts in the pathological physiology of cellulite are to some extent contradictory and inconclusive; however, some studies point to structural changes in the dermis and subcutaneous tissue. A correlation of cellulite with focal hypertrophic subcutaneous connective tissue strands and lower density of connective tissue septa in subcutaneous tissue also point to changes in the related gluteal fascia and thus in the closely interlaced gluteal muscles. A rapid degenerative development of the muscle dynamics that were originally gained over generations unquestionably occurs in the Caucasian race and its related urbanization. The gender-specific dimorphism in the subcutaneous area must also be investigated further, since almost exclusively women are affected. For this reason we have anatomically examined male and female gluteal zones and demonstrated significant genderspecific changes. In particular, a weakening of the muscle-tendon and muscle-fascia dynamics of the gluteal muscles appears to be responsible for the round, superficially visible dermal changes. The entire embryonic unit of the muscle-fascia-skin structures in the buttocks and thigh area is involved in female cellulite. A transformation of these degenerative changes through regenerativemeasures, such as active movement and shock wave therapy is, therefore, appropriate and necessary.

The easiest way to differentiate lipedema from lymphedema is to detect lipedema-associated clinical symptoms (e.g., cuffing sign, retromalleolar fat pads, tenderness of the skin). Physical examinations including the Streeten test, waist-to-height ratio, capillary fragility, and pain measurements can also aid in differential diagnosis. The last two methods can be used to follow and measure therapeutical efficacy. Imaging techniques (ultrasound, computed tomography, magnetic resonance imaging, lymphoscintigraphy, infrared fluoroscopy) and cardiovascular methods (aortic stiffness determination, three-dimensional speckle tracking echocardiography) are sensitive tools to find subtle differences.

Lipedema is a clinical entity frequently misdiagnosed or confounded with primary lymphedema. Lipedema is an adipose tissue disorder, also pathological itself, that occurs almost exclusively in obese women. It is characterized by bilateral enlargement from hip to ankle due to abnormal deposits of subcutaneous fat, usually sparing the feet. This disease usually occurs at or just after puberty. Patients may complain of pain, easy bruising of the affected areas with moderate to severe sensitivity to digital pressure or pinching, and mild edema after orthostatism. Lipedema results in considerable frustration and distress resulting from the cosmetic appearance. Imaging studies using computed tomography, magnetic resonance imaging, and lymphoscintigraphy are not indicated, except if the diagnosis is atypical or doubtful or to confirm lipedema. Long-term evolution may alter lymphatic system and lead to a lipo-lymphedema, then involving the foot, with specific complications such as cellulitis. Lipedema management is not codified and includes weight loss (which poorly improves leg appearance or discomfort), psychological counselling, compression therapy often poorly tolerated and physical activity, particularly aquatic. Liposuction using tumescent local anesthesia, may reduce edema, spontaneous pain, sensitivity to pressure, bruising and may improve appearance resulting in a notable improvement of quality of life. Clinical and physiopathological studies are still required to enable improved management of women having lipedema.

An endothelial cell monolayer separates interstitia from blood and lymph, and determines the bidirectional transfer of solutes and macromolecules across these biological spaces. We review advances in transport modalities across these endothelial barriers. Glucose is a major fuel for the brain and peripheral tissues, and insulin acts on both central and peripheral tissues to promote whole-body metabolic signalling and anabolic activity. Blood-brain barrier endothelial cells display stringent tight junctions and lack pinocytic activity. Delivery of blood glucose and insulin to the brain occurs through their respective carrier (Glucose transporter 1) and receptor (insulin receptor), enacting bona fide transcytosis. At supraphysiological concentrations, insulin is also likely transferred by fluid phase cellular uptake and paracellular transport, especially in peripheral microvascular endothelia. The lymphatic microvasculature also transports insulin but in this case from tissues to lymph and therefrom to blood. This serves to end the hormone's action and to absorb highly concentrated subcutaneously injected insulin in diabetic individuals. The former function may involve receptor-mediated transcytosis into lymphatic endothelial cells, the latter fluid phase uptake and paracellular transport. Lymphatic capillaries also mediate carrierdependent transport of other nutrients and macromolecules. These findings challenge the notion that lymphatic capillaries only transport macromolecules through intercellular flaps.

Lipedema is a fat disorder that is often misdiagnosed. It was first identified at the Mayo Clinic in 1940, but medical schools do not include it in their curriculum and is therefore poorly understood. It presents as disproportionate and symmetrical accumulations of fat (bilateral), which is often accompanied by orthostatic edema. Early diagnosis and treatment are crucial, as the disease is progressive and can lead to immobility as well as a significant decrease in the quality of life. Lipedema differs from obesity because it does not respond to diet and exercise. This article gives you a glimpse into what lipedema is about and will help you identify some differences between lipedema and lymphedema. It will also help you identify which surgical procedures have been successful in treating the disease.

The purpose of this work was to quantify 3.0 T (i) T(1) and T(2) relaxation times of in vivo human lymph nodes (LNs) and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment-related lymphedema (BCRL). MR relaxometry was performed over bilateral axillary regions at 3.0 T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T(1) maps were calculated using a multi-flip-angle (20, 40, 60°) method with B(1) correction (dual-T(R) method, T(R1) /T(R2)  = 30/130 ms), and T(2) maps using a multi-echo (T(E)  = 9-189 ms; 12 ms intervals) method. T(1) and T(2) were quantified in the LN cortex and hilum. A Mann-Whitney U-test was applied to compare LN relaxometry values between patients and controls (significance, two sided, p < 0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean ± standard deviation) in healthy controls were T(1) cortex, 1435 ± 391 ms; T(1) hilum, 714 ± 123 ms; T(2) cortex, 102 ± 12 ms, and T(2) hilum, 119 ± 21 ms. T(1) of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p < 0.001) and compared with bilateral control values (p < 0.01). The LN cortex T(1) asymmetry discriminated cases from controls (p = 0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0 T T(1) and T(2) relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.