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Lipedema is a chronic metabolic disorder of the adipose tissue, of unknown aetiology, and is marked by a bilateral and symmetrical swelling of the lower extremities, caused by extensive deposits of subcutaneous fatty tissue (local lipohypertrophy). Proliferative subcutaneous fatty tissue compresses the lymph collectors of the superficial lymphatic system. Lymphedema is characterized swelling of soft tissues by accumulation of lymphatic fluid [1]. If lipolympedema remains untreated, it will progress through the same stages as pure lymphedema [1,2]. A helpful diagnostic tool to distinguish lipedema from lymphedema is Stemmers sign. Limb circumference or volume measurements are commonly used for diagnosis and for following lymphedema progression [3]. Developing technology also brings new approaches for lymphedema diagnosis: bioimpedance, 99mTc lymphoscintigraphy, magnetic resonance lymphangiography etc. Ultrasound is recently developing imaging technique for both lymphedema diagnosis and follow up [4]. In this case report localized lipedema which diagnosed with ultrasonography, in a patient with osteoarthritis in the knee joint was discussed.

Lipoedema is a condition characterised by symmetrical lower limb enlargement. It was first described by Allen & Hines who coined the term lipoedema. The result of subcutaneous deposition of fat gives rise to fatty swelling in the buttocks, thighs and lower limbs sparing the feet. It is associated with obesity and hence upper limbs and rarely trunks are also affected.  This Clinical condition affects females predominantly 1:4 and hence has a profound effect on the psychology therefore it is not uncommon to see these patients with a low self esteem, socially isolated and depressed. Due to its resemblance to lymphoedema it is not unusual to be misdiagnosed, thus leading to a spiral of inappropriate tests and improper treatment outcome.

INTRODUCTION: Nowadays, liposuction is the most frequently performed aesthetic surgery procedure in Western Countries. This technique has had rapid development since the 1970s, when it was experimented for the first time by A. and G. Fischer. It is currently widely used in clinical practice for many different situations in aesthetic, reconstructive and functional fields. MATERIALS AND METHODS: This review aims to describe the historical evolution of liposuction by analyzing the transformation of the method in function of the introduction of innovative ideas or instruments. We have also focused on reporting the major clinical applications of this surgical technique, applicable to almost the entire body surface. We finally analyzed the complications, both major and minor, associated with this surgical technique. RESULTS: Liposuction is mainly used to correct deep and superficial fat accumulations and remodel the body contour. It has become an essential complementary technique to enhance the aesthetic result of many other aesthetic procedures such as reduction mammoplasty, abdominoplasty, brachioplasty, thigh lift and post bariatric body contouring. However, it can be largely used for the treatment of innumerable pathologies in reconstructive surgery such as lipomas, lipedema, lipodystrophies, pneudogynecomastia and gynecomastia, macromastia e gigantomastia, lymphedema and many others. The complication rate is very low, especially when compared with conventional excisional surgery and the major, complications are generally associated with improper performance of the technique and poor patient management before and after surgery. CONCLUSION: Liposuction is a safe, simple and effective method of body contouring. It has enormous potential for its application in ablative and reconstructive surgery, far from the most common aesthetic processes with a very low complication rate.

Lipedema an often overlooked but treatable disease Lipedema is a painful disease that affects some women between puberty and menopause through a subcutaneous fat accumulation especially in the lower extremities. Patients suffer from pain and pressure tenderness. The larger fat accumulation, especially on the inside of the thighs and knees, causes walking difficulties. This can successfully be treated by liposuction with good long-term results in terms of pain reduction and prevention of osteoarthritis development in the knee and ankle joints.

Lipoedematous scalp (LS) is an extremely rare condition characterised by a soft and boggy consistency in the scalp due to an increased layer of subcutaneous tissue.In this report, we present a case of LS in a 64-year-old Indian woman. Clinical examination revealed only vague boggy lumpiness involving the whole of occipital scalp extending to parietal scalp. MRI scalp showed diffuse fatty infiltration of the scalp, particularly at the posterior parietal and occipital convexity extending to both lateral aspects of the cranium, with homogeneous signal in keeping with fat. Incidentally MRI also found diffuse fatty infiltration of the parotids.The aethiopathogenesis of LS is still unknown, however it is believed that the hormone leptin could be the key hormone in the dysregulation of fat deposition and distribution. This case report highlights the subtle features with which these cases can present and explores the literature on reported cases of LS.

Liposuction is a procedure commonly performed in the UK usually with a low incidence of serious sequelae; however with larger patients and increased volumes of lipoaspirate, complications have been reported more frequently. One of the rare but very serious complications postliposuction is fat embolism syndrome (FES), a life-threatening condition difficult to diagnose and limited in treatment. The authors present the case of a 45-year-old woman who was admitted to the intensive care unit postelective liposuction for bilateral leg lipoedema. She presented with the triad of respiratory failure, cerebral dysfunction and petechial rash requiring a brief period of organ support. This case highlights that with the recent increase in liposuction procedures worldwide, FES is a differential to always consider. Although still a rare condition this article emphasises the importance of thinking outside the box and how to identify and manage such a lifethreatening complication.

BACKGROUND: Lipedema is a condition consisting of painful bilateral increases in subcutaneous fat and interstitial fluid in the limbs with secondary lymphedema and fibrosis during later stages. Combined decongestive therapy (CDT) is the standard of care in most countries. Since the introduction of tumescent technique, liposuction has been used as a surgical treatment option. The aim of this study was to determine the outcome of liposuction used as treatment for lipedema. METHODS: Twenty-five patients who received 72 liposuction procedures for the treatment of lipedema completed a standardized questionnaire. Lipedema-associated complaints and the need for CDT were assessed for the preoperative period and during 2 separate postoperative follow-ups using a visual analog scale and a composite CDT score. The mean follow-up times for the first postoperative follow-up and the second postoperative follow-up were 16 months and 37 months, respectively. RESULTS: Patients showed significant reductions in spontaneous pain, sensitivity to pressure, feeling of tension, bruising, cosmetic impairment, and general impairment to quality of life from the preoperative period to the first postoperative follow-up, and these results remained consistent until the second postoperative follow-up. A comparison of the preoperative period to the last postoperative follow-up, after 4 patients without full preoperative CDT were excluded from the analysis, indicated that the need for CDT was reduced significantly. An analysis of the different stages of the disease also indicated that better and more sustainable results could be achieved if patients were treated in earlier stages. CONCLUSIONS: Liposuction is effective in the treatment of lipedema and leads to an improvement in quality of life and a decrease in the need for conservative therapy.

This study aimed to explore patients' perceptions regarding the impact that lower limb chronic oedema has on their quality of life (QoL). A quantitative descriptive design was used to collect data from patients with lower limb chronic oedema. A condition-specific validated questionnaire was distributed to a purposive sample (n = 122) through manual lymphatic drainage/vascular/health clinics in Ireland. Results indicated that patients with lower limb chronic oedema experience a wide range of physical problems such as limb heaviness (74%, n = 66), weakness (44%, n = 40) and pain (38%, n = 34). Additionally, difficulties with walking (53%, n = 48), standing (51%, n = 46) and bending (45%, n = 40) were reported. Concerns regarding poor body image were strongly evident (76%, n = 68). Difficulties finding clothing/footwear to fit oedematous limb(s) were reported (59%, n = 53), in addition to finding clothes that participants would like to wear (64%, n = 58). Emotional symptoms of irritability (42%, n = 38), anxiety (41%, n = 37) and tension (40%, n = 36) were reported. Over half of the participants (55%, n = 49) stated that their chronic swelling affected their social functioning and their ability to engage in leisure activities. This study has identified that lower limb chronic oedema has significant psychological, social and physical implications for persons' QoL.

Background: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)., Methods and Results: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages., Conclusion: Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.

The lymphatic system regulates tissue fluid homeostasis, intestinal fat absorption, and immune cell trafficing. Lymphedema is soft tissue swelling secondary to lymphatic dysfunction, which results in the accumulation of tissue fluid in the interstitial space. This might occur as a primary disorder of the developing lymphatic system, or alternatively lymphedema might be an acquired disorder secondary to lymphatic injury. For example, secondary lymphedema is a common problem following cancer and cancer treatments such as lymph node surgery and radiotherapy, resulting in significant morbidity. Radiotherapy is an established risk factor for lymphedema, and in addition to causing direct injury to the lymphatic vessel, it is possible that alternative mechanisms might also contribute to radiation-induced lymphatic dysfunction, such as localized ischemia of the lymphatic wall. It is also likely that predisposing genetic risk factors are at play, as not all individuals exposed to the same risk factors will develop secondary lymphedema. Lipoedema is a different form of soft tissue swelling due to the abnormal accumulation of adipose tissue. Lipoedema and lymphatic dysfunction appear to be linked, as individuals frequently develop a degree of lymphedema, particularly as the condition progresses in severity, where it may be decribed as lipo-lymphedema. The cause of lipoedema and the genetic basis of the condition are currently unknown. This thesis aims to discover and define alternative mechanisms for lymphtic dysfunction in the context of secondary lymphedema, particularly focussing on the supply of oxygenated blood to the lymphatic vessel wall. We also aim to describe inheritance patterns and the genetic factors involved in lipoedema and lipo-lymphedema. Such knowledge might uncover therapeutic targets and facilitate the development of treatments for lymphedema and lipoedema, including gene therapy.

Das Lipödem ist gekennzeichnet durch eine dispropor tionale Vermehrung des subkutanen Fettgewebes an Hüf ten, Beinen und Armen. Von der asymptomatischen Lipo hypertrophie unterscheidet es sich durch das Vorhandensein der typischen Symptome (Spontan und Berührungsempfindlichkeit, Ödeme). Auch wenn die Pathogenese des Lipödems immer noch weitgehend unbe kannt ist, deutet vieles darauf hin, dass neben hormonel len Faktoren entzündliche Prozesse eine wesentliche Rolle spielen. Dabei ist nicht geklärt, ob und in welcher Weise diese selbst ursächlich für das Auftreten des Lipödems sind oder Folge anderer körperlicher Veränderungen wie Adipositas oder hormoneller Dysbalancen. Der Circulus vitiosus aus Adipositas, die bei über der Hälfte der Patientinnen vorliegt, und der sich hierdurch entwickelnden Hyperinsulinämie bewirkt nicht nur eine weitere Fettgewebszunahme, sondern wirkt über die Zyto kine des viszeralen Fettgewebes auch proinflammatorisch und ödemfördernd,

EXECUTIVE SUMMARY Lipedema is a chronic condition that occurs almost exclusively in women and manifests as symmetrical buildup of painful fat and swelling in the limbs, sparing the hands and feet. A critical issue is the poorly understood disease biology, which for diagnosed patients results in limited treatment options that, at best, ameliorate the symptoms of lipedema. Individuals who suffer from the disease are further impacted by the absence of diagnostic tools, the lack of public and medical awareness of lipedema, and the stigma associated with weight gain. As a result, the true number of women with lipedema, or its epidemiology, is unknown. Braving these challenges is an active, numerous, and engaged patient community eager to participate in lipedema research. Supported by equally devoted caregivers and researchers, the lipedema field presents an immense opportunity for scientific and medical advancements. To capitalize on this potential, the Lipedema Foundation and the Milken Institute’s Center for Strategic Philanthropy convened leading stakeholders to discuss the current state of lipedema science and identify the key philanthropic research opportunities to advance the field. Little is known about how and why lipedema develops in a patient. Although the disease is reported to occur during puberty and other periods of hormonal changes, why this happens is not understood. The painful fat and swelling in some patients can be so debilitating that their mobility is impaired; yet what drives these symptoms is unknown. Psychosocial issues are also prevalent in women with lipedema, contributing to health burden and complexity of disease management. Furthermore, many patients develop the disease alongside obesity; however, diet, exercise, and weight loss surgery have limited effect on lipedema fat. Although the lack of disease biology is staggering, philanthropic investments in research can leverage the desire of patients to participate in studies to improve their and the entire field’s understanding of lipedema. The convergence of multiple scientific topics around lipedema indicates that addressing these gaps in research will also improve the understanding of hormone, pain and edema, mental health, and metabolic biology. There are no diagnostic tools or tests for lipedema. Diagnosis of lipedema involves a clinical assessment and discussion of the individual’s medical history, a process that is difficult to scale within the current healthcare system. The absence of diagnostic tools to streamline or confirm a clinical diagnosis is a key unmet need, which if addressed by philanthropy, has the potential to dramatically change the trajectory of the disease. Investing in research efforts to advance novel imaging technologies to diagnose lipedema is a promising research avenue that would simultaneously benefit individuals who suffer from the disease and healthcare providers unfamiliar with the condition. The public and medical community are not aware of lipedema. Lipedema was initially described in 1940, yet little knowledge about the disease has permeated the general public, with a concomitant lack of mention in the educational curriculum of medical trainees. Addressing this challenge will require philanthropic efforts to define the disease from a basic, clinical, and diagnostic perspective. A key philanthropic opportunity is support for a lipedema patient registry linked to a tissue biorepository. This effort has the potential to generate and support the needed disease research, while engaging patients as partners in understanding the science of lipedema.

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