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Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Background: The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. Methods: We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise cooccurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease–disease interrelationships. Results: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease–disease interrelationships was noted in all three lymphatic categories when compared to the control population.

Recommendations: 1.1 Evidence on the safety of liposuction for chronic lipoedema is inadequate but raises concerns of major adverse events such as fluid imbalance, fat embolism, deep vein thrombosis, and toxicity from local anaesthetic agents. Evidence on the efficacy is also inadequate, based mainly on retrospective studies with methodological limitations. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page. 1.2 Further research should report: • patient selection, including age, effects of hormonal changes (which should include effects seen during puberty and menopause) and the severity and site of disease • details of the number and duration of procedures, the liposuction technique used (including the type of anaesthesia and fluid balance during the procedure), and any procedure-related complications • long-term outcomes, including weight and body mass index changes • patient-reported outcomes, including quality of life. 1.3 Patient selection should be done by a multidisciplinary team, including clinicians with expertise in managing lipoedema. 1.4 The procedure should only be done in specialist centres by surgeons experienced in this procedure.

Background: An adequate dietary energy supply is particularly important in patients with lipedema as it promotes weight and fat loss. Accurate estimation of resting metabolic rate (RMR) allows implementing a proper calorie restriction diet in patients with lipedema. Therefore, an accurate assessment of energy demand in patients with lipedema is crucial in clinical practice. Our study aimed to compare actual resting metabolic rate (aRMR) with predicted resting metabolic rate (pRMR) in women with lipedema and to determine the association between individual anthropometric measurements and aRMR.Methods: A total of 108 women diagnosed with lipedema were enrolled in the study. aRMR was measured by indirect calorimetry (IC) using FitMate WM metabolic system (Cosmed, Rome, Italy). pRMR was estimated with predictive equations and BIA. All anthropometric measurements were based on BIA (bioelectric impedance analysis).Results: The mean aRMR in the study group was 1705.2 ± 320.7 kcal/day. Most methods of predicted RMR measurement used in our study significantly underpredicted aRMR in patients with lipedema. We reported statistically significant high correlations between all anthropometric measurements and aRMR/pRMR and a moderate correlation between visceral fat level (VFL) and aRMR. Conclusions: aRMR in patients with lipedema calculated with predictive equations was significantly lower than aRMR measured with other methods. This study found the agreement of predictive equations compared to IC is low (<60%). Fat-free mass (FFM) is a stronger determinant of RMR in patients with lipedema than fat mass.

Attention has been drawn to the role of changes in visceral adipose tissue rather than subcutaneous adipose tissue in the relationship between adipokines and dysfunctional adipose tissue. Especially in lipedema in which subcutaneous adipose tissue is affected, information about adipokines is insufficient. In this study, it was aimed to investigate adiponectin, ghrelin, resistin and visfatin levels and their relationship with adipose tissue thickness in patients with lipedema. For this purpose, subcutaneous adipose tissue thickness was evaluated objectively by ultrasonography. A total of 19 female patients diagnosed with lipedema and 15 healthy women with no age difference were included in the study. Skin and subcutaneous adipose tissue thickness were measured ultrasonographically. Serum levels of adiponectin, ghrein, resistin and visfatin of all subjects were measured using sandwich ELISA protocol. In patients with lipedema, subcutaneous subcutaneous tissue thickness and total skin-subcutaneous thickness were significantly increased in the thigh and calf, excluding skin thickness in the thigh, compared to controls (P0.05). No significant correlation was found between adiponectin, ghrelin, resistin and visfatin and skin, subcutaneous and total thickness measurements by ultrasound in patients with lipedema and controls (P>0.05). Although not statistically significant, when examined in detail, positive or negative correlations were observed between the groups in the relationship between adipokines and ultrasound measurements. According to our findings, although no significant relationship was found between serum levels of adipokines and subcutaneous adipose tissue thickness, it is controversial that they are completely unrelated. Further studies in larger series will shed light on the relationship between adipokines and subcutaneous tissue thickness and the importance of ultrasonography. , Adipokinler ve disfonksiyonel yağ dokusu arasındaki ilişkide subkutan yağ dokusundan ziyade viseral yağ dokusundaki değişikliklerin rolüne dikkat çekilmiştir. Özellikle cilt altı yağ dokusunun etkilendiği lipödemde adipokinler hakkında bilgi yetersizdir. Bu çalışmada lipödemli hastalarda adiponektin, ghrelin, resistin ve visfatin düzeylerinin ve bunların yağ doku kalınlığı ile ilişkisinin araştırılması amaçlandı. Bu amaçla cilt altı yağ dokusu kalınlığı ultrasonografi ile objektif olarak değerlendirildi. Lipödem tanısı almış toplam 19 kadın hasta ve yaş farkı olmayan 15 sağlıklı kadın çalışmaya dahil edildi. Deri ve deri altı yağ dokusu kalınlıkları ultrasonografik olarak ölçüldü. Tüm deneklerin serum adiponektin, ghrein, resistin ve visfatin seviyeleri sandviç ELISA protokolü kullanılarak ölçüldü. Lipödemli hastalarda, uyluk ve baldırda subkutan subkutan doku kalınlığı ve toplam deri-subkutan kalınlığı kontrollere kıyasla, uyluktaki deri kalınlığı dışında önemli ölçüde arttı (P0.05). Lipödemli hastalarda ve kontrollerde ultrason ile adiponektin, ghrelin, resistin ve visfatin ile deri, deri altı ve toplam kalınlık ölçümleri arasında anlamlı bir ilişki bulunmadı (P>0.05). İstatistiksel olarak anlamlı olmasa da detaylı incelendiğinde adipokinler ve ultrason ölçümleri arasındaki ilişkide gruplar arasında pozitif veya negatif korelasyonlar gözlendi. Bulgularımıza göre, serum adipokin düzeyleri ile deri altı yağ dokusu kalınlığı arasında anlamlı bir ilişki bulunmamakla birlikte, tamamen ilgisiz oldukları tartışmalıdır. Daha geniş serilerde yapılacak çalışmalar adipokinlerin cilt altı doku kalınlığı ile ilişkisine ve ultrasonografinin önemine ışık tutacaktır.

Lipoedema has received increased attention in recent years. Overlaps with obesity sometimes make it difficult to differentiate. However, this is important for a differentiated targeted therapy. Definition and clinic Lipoedema is a painful, genetic, exces sive increase in adipose tissue on the extremities in women. This leads to a disproportion of the body. The first symptoms often manifest themselves in puberty, the course is usually progressive. Characteristic symptoms are pain at rest and pressure, tendency to hematoma, feelings of tension and swelling, rapid fatigue of the muscles and edema, which are inconsistent depending on the stage. 25–88 % of lipoedema patients suffer from obesity at the same time. Prevalence Depending on the study, 5–9.7 %, corresponding to 2–4 million women in Germany. Etiology Family disposition is obvious. Hormonal changes are trigger factors and suggest hormonal influences. In the tissue there is a slight chronic inflammation (silent inflammation), which explains the symptoms. Diagnosis The diagnosis is made clinically and must be distin guished from other fat distribution disorders. The BMI is not suitable. The waist circumference-size quotient (BCG = WHtR Waist to Height-Ratio) should be used. Therapy interdisciplinary therapeutic approach,which inaddi tion to conservative decongestion therapy, surgical therapy by liposuction also includes nutrition, exercise and psychotherapy.

Lipedema PubMed published article

El lipedema es un trastorno crónico que se presenta en mujeres durante la pubertad u otros momentos de cambios hormonales como en el embarazo o la menopausia.  Es caracterizado por una obesidad desproporcionada de las extremidades, especialmente en caderas y piernas, asociado a hematomas con mínimo trauma y dolor espontáneo o inducido por presión. Usualmente es mal diagnoticado e infratratado y suele confundirse con otras enfermedades como la obesidad y linfedema. Su causa aún se sigue estudiando, existen hipótesis sobre su origen poligenético regulado por los estrógenos, por el inicio de la enfermedad en etapas de cambio hormonal y debido a que se presenta mayormente en mujeres. Los tratamiento para el lipedema se basa en seis pilares: 1) Fisioterapia-ejercicios, 2) Terapia compresiva, 3) Control de peso, 4) Liposucción, 5) Terapia psicosocial-6) Automanejo.

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

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.

Left ventricular (LV) twist is defined as the wringing motion of the LV around its long-axis during systole generated by rotation of the LV apex in a counterclockwise direction, as viewed from the apex, while the LV base moves in a clockwise direction. In several cases, the LV apex and base move in the same direction during ejection demonstrating a special condition called as LV 'rigid body rotation'. The present review aimed to summarize our knowledge about this rare but not fully understood entity demonstrating its theoretic pathophysiologic background, clinical significance, associated diseases, and reversibility based on available literature.

BACKGROUND: Lipedema often remains undiagnosed in patients with obesity, leading to mismanagement of treatment. Because of this, despite remarkable weight loss after bariatric surgery and decreases in hip and abdomen circumference, some patients show only small decreases in circumference of the extremities and report persistent limb pain. OBJECTIVE: The goal of this work is to raise awareness of lipedema coincident with obesity, mistakenly diagnosed as obesity alone, in order to ensure the correct diagnosis of the condition and to achieve better treatment outcomes for people with lipedema and coincident obesity. SETTING: CG Lympha Clinic, Cologne, and Ernst von Bergmann Clinic, Potsdam. METHODS: From clinical records, we identified 13 patients who were diagnosed with lipedema only after undergoing bariatric surgery. We describe the course of their pain before and after bariatric surgery, focusing on the long-term progression of symptoms accompanying the disease. RESULTS: Lipedema cannot be cured by bariatric surgery, and although the patients in this study lost an average of more than 50 kg of weight, they displayed no improvement in the pain symptoms typical of lipedema. CONCLUSIONS: Because of the different etiologies of lipedema and obesity, lipedema requires its own specific treatment. Patients suffering from obesity should always be assessed for pain and lipedema. If coincident lipedema is diagnosed, we suggest that bariatric surgery only be performed first if diet and exercise have failed, the patient's body mass index is >40 kg/m2, and the patient has been informed of the possible persistence of pain. Lipedema, like a coincident disease, must be additionally treated conservatively or preferably surgically. This optimized treatment may help to better manage patient expectations after weight loss.

This book is written as a guide for patients suffering from lipedema. Known as a common, painful fat distribution disorder characterised by a disproportional fat accumulation, lipedema represents an unmet medical need where scientific evidence on both pathophysiology and its treatment is still lacking. As the number of affected patients is increasing, besides striving to map the conundrum of clinical signs and relate these to their underlying mechanisms, developing standardised approaches addressing both fat mass reduction and body contouring are key issues able to warrant therapeutic success. In this book, our intention was to look at this complex disease from all its actual perspectives and provide a concise summary of the actual state of knowledge for all those affected. After looking into the most actual data on the aetiology, pathophysiology and course of the disease, the book then focuses on our complex treatment protocols wherecurrent conservative and surgical treatment options are systematically analyzed, considering their long-term chances of success as well as associated risks and side effects. We propose a three step treatment approach. 1st step initiates with weight control and addresses obesity, if present. 2nd step is an individual liposuction therapy plan to treat all lipedema areas, and more. 3rd step includes body contouring surgery, only in patients with massive skin laxity after liposuction and / or massive weight loss. Table of Contents Front Matter Pages i-xviii The Lipedema Zaher Jandali, Benedikt Merwart, Lucian Jiga Pages 1-68 The Lymphedema Corrado Campisi, Lucian Jiga, Zaher Jandali Pages 69-94 Treatment of Lipedema Zaher Jandali, Benedikt Merwart, Ralf Weise, Angel Pecorelli Capozzi, Lucian Jiga Pages 95-176 Body Contouring Surgery After Extensive Liposuction and Weight Loss Zaher Jandali, Benedikt Merwart, Lucian Jiga Pages 177-198 Additional Information about Treatment Zaher Jandali, Benedikt Merwart, Lucian Jiga Pages 199-204 Back Matter Pages 205-207

Background: Lipedema is a chronic and progressive adipose tissue disorder that causes significant morbidity and negatively influences mental health and quality of life, and increases the risk of depression, anxiety, and eating disorders. One construct of relevance to better understanding psychological disorders is emotion regulation (ER). Therefore, the aim of this study is to investigate the difficulties in ER among lipedema patients compared to healthy people without lipedema. Methods: This cross-sectional study assessed differences in ER and anxiety between two groups: 26 female patients with lipedema and 26 sex- and age-matched healthy controls. The Difficulties in Emotion Regulation Scale (DERS) assessed emotional regulation across six dimensions: Impulse control, goal-directed behavior, awareness, clarity, non-acceptance, and strategies. Anxiety was assessed by the Hamilton Anxiety Scale (HAM-A). ANOVA assessed differences in measures between lipedema and healthy control groups. Results: Lipedema patients presented with significantly more difficulties in ER and a higher level of anxiety than those without lipedema. Specifically, the lipedema group showed higher and significant differences in total DERS and anxiety scores and all DERS subscales scores compared to those without lipedema. Conclusions: Lipedema patients showed significant difficulties with ER, and were associated with anxiety symptoms, indicating that ER difficulties may play a role in developing emotional disorders, such as anxiety, for patients with lipedema. The health care provider should pay more attention to ER difficulties and psychological status among lipedema patients.

Lipedema patients suffer not only from visual stigma but also reduction in their quality of life through pain and performance loss in daily life. In clinical practice, it is still difficult to reliably diagnose the disease. This study aims to provide further insights into the characteristics of lipedema patients of all stages and provide a baseline prior to surgery for a surgical treatment evaluation by means of patient-reported outcome measures. Methods: Patients completed a lipedema-specific questionnaire containing 50 items, the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). The data were analyzed using SPSS statistics 27. Patients who had already received liposuction were excluded. Results: Five hundred and eleven patients were included, of whom 337 completed the PHQ9 and 333 completed the WHOQOL-BREF questionnaires. The general characteristics of lipedema patients, especially the daily symptoms, are described. Previous observations, such as the frequent occurrence of hypothyroidism and the low rate of type 2 diabetes, were confirmed. Over 49% suffer from severe impairments in their jobs, whereby the disease shows a familial accumulation. The results of the WHOQOL-BREF and the PHQ-9 suggest a high level of mental stress. Discussion: As surgical intervention in lipedema patients is gaining traction, its effects should be well-documented. Therefore, a comprehensive baseline needs to be established prior to surgical treatment. The psychological components are just as important as the inclusion of daily impairments.