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The invention provides carbazole derivatives for the treatment of fibrotic diseases (pathological collagen deposition) in tissues and organs, and related symptoms, and conditions thereof.

Lipoedema is a chronic progressive adipose disorder that affects mainly women and presents as symmetrical enlargement of the buttocks and legs. It is commonly misdiagnosed as obesity or lymphoedema, but careful assessment will reveal a disproportionate enlargement below the waist which is resistant to dieting, sparing of the feet, legs are tender or painful to touch and bruise easily, there is occasional orthostatic oedema, and there is often significant psychological morbidity. Lipoedema is a oestrogen-regulated condition with onset around puberty in 78% of women, and there is often a strong family history. The condition is exacerbated by weight gain and there is increasing anecdotal evidence that women who are obese are seeking a diagnosis of lipoedema, either to procure NHS funded manual lymphatic drainage, or to medicalise their obesity and avoid acknowledging that the responsibility for their weight gain is lifestyle orientated. Management of lipoedema consists of accurate diagnosis, psychological care, management of orthostatic oedema, and prevention of progression through skin care and weight management.

Lipedema, or adiposis dolorosa, is a common adipose tissue disorder that is believed to affect nearly 11% of adult women worldwide. It is characterized most commonly by disproportionate adipocyte hypertrophy of the lower extremities, significant tenderness to palpation, and a failure to respond to extreme weight loss modalities. Women with lipedema report a rapid growth of the lipedema subcutaneous adipose tissue in the setting of stress, surgery, and/or hormonal changes. Women with later stages of lipedema have a classic "column leg" appearance, with masses of nodular fat, easy bruising, and pain. Despite this relatively common disease, there are few physicians who are aware of it. As a result, patients are often misdiagnosed with lifestyle-induced obesity, and/or lymphedema, and subjected to unnecessary medical interventions and fat-shaming. Diagnosis is largely clinical and based on criteria initially established in 1951. Treatment of lipedema is effective and includes lymphatic support, such as complete decongestive therapy, and specialized suction lipectomy to spare injury to lymphatic channels and remove the diseased lipedema fat. With an incidence that may affect nearly 1 in 9 adult women, it is important to generate appropriate awareness, conduct additional research, and identify better diagnostic and treatment modalities for lipedema so these women can obtain the care that they need and deserve.

Lipoedema is a long-term, progressive condition, usually presenting as symmetrical enlargement of the legs and buttocks, and mainly affecting women. Distinct from obesity or lymphoedema, lipoedema is associated with an unusual distribution and proliferation of diet-resistant inflammatory fat tissue. This article provides background to lipoedema diagnosis and discusses self-care support for women with lipoedema.

BACKGROUND: Long-term results following liposuction in patients with lipoedema are available only for an average period of 4 years. OBJECTIVE: To find out whether the improvement of complaints persists for a further 4 years. METHODS: In a single-centre study, 85 patients with lipoedema had already been examined after 4 years. A mail questionnaire - often in combination with clinical controls - was repeated after another 4 years (8 years after liposuction). RESULTS: Compared with the results after 4 years, the improvement in spontaneous pain, sensitivity to pressure, oedema, bruising and restriction of movement persisted. The same held true for patient self-assessment of cosmetic appearance, quality of life and overall impairment. Eight years after surgery, the reduction in the amount of conservative treatment (combined decongestive therapy, compression garments) was similar to that observed 4 years earlier. CONCLUSION: These results demonstrate for the first time the long-lasting positive effects of liposuction in patients with lipoedema.

Compression therapy is a key component in the effective management of people with lower limb problems associated with venous, lymphatic and fat disorders such as lipoedema. Individuals with lymphoedema, venous ulceration and lipoedema often require long-term compression therapy to prevent and manage problems such as chronic ulceration and skin changes, persistent swelling and shape distortion. Challenges remain in achieving acceptable, safe, effective and cost-efficient compression therapy choices. Adjustable compression wrap devices using hook and loop fasteners, commonly called VELCRO brand fasteners, present new opportunities for improving treatment outcomes, supporting patient independence and self-management in the use of compression therapy. This paper reports the findings of an evidence review of adjustable compression wrap devices in people with lymphoedema, chronic oedema, venous ulceration and lipoedema. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

While there is no proven cure for lipoedema, early detection is key as specialist treatments, complemented by self-management techniques, can improve symptoms and prevent progression. There is no universal approach as the correct treatment or treatments will depend on each patient's particular circumstances; however, when chosen early and appropriately, interventions can provide huge benefits. The most common treatments in the management of lipoedema include compression, manual lymphatic drainage (MLD), tumescent liposuction, intermittent pneumatic compression therapy (IPC), kinesio taping, deep oscillation therapy, and cognitive behavioural therapy (CBT).

Selecting the most appropriate compression garments is vital in the long-term management of venous disease and chronic oedema. The range of styles has improved greatly over the years and many garments are available on the UK Drug Tariff. Practitioners now have a wide range of options to choose from including the type of fabric, colour, compression class, and style of garment. These options increase the pratitioner's ability to select the most suitable garments and combine clinical and aesthetic needs, with the ultimate aim of improving compliance. The focus of this article is to highlight the aims and qualities of the various types of compression garments available, discuss the rationale for prescribing choice, and describe the benefits of Haddenham's Veni made-to-order compression leg garments in the management of chronic oedema and venous disease. Three case studies will demonstrate the effectiveness of the Veni made-to-order range of compression garments.

Lipedema is a chronic disorder characterized by abnormal distribution of subcutaneous adipose tissue on the proximal extremities, pain and capillary fragility. Its etiology is unknown but in analogy to central obesity, chronic low-level inflammation in adipose tissue has been suggested. There seems to be an increased propagation of pre-adipocytes into mature adipocytes contributing to the massive enlargement of subcutaneous adipose tissue. We investigated whether tyrosine kinases might be involved. Proteins from adipose tissue harvested during microcannular tumescent liposuction in lipedema and in lipomas were subjected to 10% polyacrylamide-gel, transferred to a polyvinylidenfluorid membrane and immunoblotted with indicated P-Tyr-100 antibody followed by enhanced chemiluminescence reaction. A survey of all blots did not reveal tyrosine-phosphorylated proteins with a molecular weight >100 kD in lipedema tissue and controls. These investigations suggest absence of activated growth factor receptors. Some signals indicating unspecific tyrosine-phosphorylation of smaller proteins were detected in tissue of both lipedema patients and controls. The present data suggest that there is no enduring activation of tyrosine kinase pathways of adipogenesis in lipedema as in lipoma controls.

PURPOSE: Lipoedema is a chronic, progressive adipose disorder of unknown etiology, often underdiagnosed or misdiagnosed as obesity. It manifests itself with accumulation of the fat in lower parts of the body and associated edema and, due to numerous physical and psychological consequences, affects the quality of life (QOL) of those who suffer. The aim of this study was to investigate the psychological factors that might have an impact on the QOL of women with lipoedema from the contextual behavioral viewpoint. METHODS: In an Internet-based cross-sectional study, women suffering from lipoedema (N = 120) were asked to fill in questionnaires assessing: symptom severity, QOL (WHOQOL-BREF), satisfaction with life (SWLS), psychological flexibility (Acceptance and Action Questionnaire-II), social connectedness (Social Connectedness Scale-Revised) and other psychological factors. The majority of participants were from the USA, the UK, and Australia. RESULTS: Multiple hierarchical regression analyses showed that a higher level of QOL was predicted by higher levels of psychological flexibility and social connectedness, while controlling for symptom severity. Higher level of SWL was predicted only by higher level of social connectedness. CONCLUSIONS: Acceptance and Commitment Therapy with psychological flexibility as the target of change and Functional Analytic Psychotherapy with social connectedness as the target of change might be useful in treating women with lipoedema; however, further research in this area is needed. The authors conclude that psychological and biomedical interventions for women with lipoedema and their QOL merit more attention from researchers and the medical community than is currently received.

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g. , magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.

Lymphoscintigraphy has emerged as the diagnostic test of choice differentiating lymphoedema from other causes of extremity swelling in adult and paediatric patients with a high clinical suspicion of impaired lymphatic function. In paediatric patients who present with lymphoedema, primary lymphoedema accounts for the majority of the cases, with prevalence estimates that approximate 1.15/100,000 persons aged less than 20 years. Other causes of lymphoedema include combined lymphatic vascular diseases and to a lesser extent, secondary lymphoedema due to surgical and non-surgical trauma to the lymphatic system. Lymphoscintigraphy plays an important role in the direction of clinical management in these patients with lymphoedema and proper recognition of lymphoscintigraphic patterns in this population is essential. Sentinel lymph node localization and biopsy has become standard of care in adult patients with melanoma and breast cancer. It is recommended in paediatric and adolescent patients with melanoma, peripheral rhabdomyosarcomas, and several specific soft tissue sarcomas.

Lipedema is an uncommon disorder characterized by localized adiposity of the lower extremities, often occurring in females with a family history of the condition. The adiposity extends from hips to ankles and is typically unresponsive to weight loss. In addition to the aesthetic deformity, women also describe pain in the lower extremities, particularly with pressure, as well as easy bruising. Although the condition is well described, it is relatively rare and often misdiagnosed. The purpose of this review is to describe the initial evaluation and diagnosis of lipedema and discuss treatment options.