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Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.

Dr. Allen and Dr. Hines pioneered and first described lipedema in the 1940s, a common subcutaneous adipose tissue disorder characterized as enlargement of both lower extremities. Lipedema is not edema; it is a genetically determined disturbance in adipose tissue mass and adipose tissue distribution.[1][2][3][4] In 1951 a second seminal paper provided more description of lipedema. Fat distribution involves lower extremities, upper arms, hips, buttocks, thighs sparing trunks, and feet.[2] Lower extremities are characterized by pain, easy bruisability, firm subcutaneous nodules of adipose tissue, and resistance of fat to traditional diet and exercise.[5][6]

Lipoedema UK welcomed our involvement with NICE and the opportunity to comment on noncosmetic liposuction (NCL) as a proposed interventional procedure for chronic lipoedema. In response, we have been proactive in capturing the views and experiences of individuals in the UK living with lipoedema and from those who have undergone non-cosmetic liposuction.

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated by autonomic nerves (ANs) (sympathetic and parasympathetic nerves) and SNs. Recent studies have shown that the nerves innervating the tumor microenvironment establish intimate communications with tumors, producing various stimuli for tumors to progress and disseminate. In this review, our current understanding of the role of SNs innervating bone in the pathophysiology of CABP will be overviewed. Then the hypothesis that SNs facilitate cancer progression in bone will be discussed in conjunction with our recent findings that SNs play an important role not only in the induction of CABP but also the progression of bone metastasis using a preclinical model of CABP. It is suggested that SNs are a critical component of the bone microenvironment that drives the vicious cycle between bone and cancer to progress bone metastasis. Suppression of the activity of bone-innervating SNs may have potential therapeutic effects on the progression of bone metastasis and induction of CABP.

(1) Background: Lipoedema is a disease characterized by excessive bilateral and symmetrical accumulation of subcutaneous tissue in the lower extremities. It is a poorly understood condition, and low awareness of its existence often leads to incorrect diagnosis Initially, lipoedema was considered to be completely independent of lifestyle Currently, however, more and more cases of the coexistence of lipoedema and obesity are described in the literature as additionally affecting the severity of the disease The aim of the review is to present lipoedema as a social problem. (2) Methods: Materials on lipoedema in the social context were selected from 2018-2021. The PRISMA-Scr checklist was used in the review. (3) Results: Research has shown that more than 3/4 of patients with lipoedema are also overweight or obese. Patients with lipoedema have many comorbidities, and their presence negatively affects the quality of life. The quality of life in patients with lipoedema is lower than in healthy patients. (4) Conclusions: The number of studies available on lipoedema is low. Obesity is common in patients with lipoedema. Mental disorders increase the level of experienced pain. Lipoedema significantly reduces quality of life. A healthy lifestyle in patients with lipoedema could be helpful for prevention of complications and disability.

Whole-body three-dimensional surface imaging (3DSI) offers the ability to monitor morphologic changes in multiple areas without the need to individually scan every anatomical region of interest. One area of application is the digital quantification of leg volume. Certain types of morphology do not permit complete circumferential scan of the leg surface. A workflow capable of precisely estimating the missing data is therefore required. We thus aimed to describe and apply a novel workflow to collect bilateral leg volume measurements from whole-body 3D surface scans regardless of leg morphology and to assess workflow precision. For each study participant, whole-body 3DSI was conducted twice successively in a single session with subject repositioning between scans. Paired samples of bilateral leg volume were calculated from the 3D surface data, with workflow variations for complete and limited leg surface visibility. Workflow precision was assessed by calculating the relative percent differences between repeated leg volumes. A total of 82 subjects were included in this study. The mean relative differences between paired left and right leg volumes were 0.73 ± 0.62% and 0.82 ± 0.65%. The workflow variations for completely and partially visible leg surfaces yielded similarly low values. The workflow examined in this study provides a precise method to digitally monitor leg volume regardless of leg morphology. It could aid in objectively comparing medical treatment options of the leg in a clinical setting. Whole-body scans acquired using the described 3DSI routine may allow simultaneous assessment of other changes in body morphology after further validation.

Objective: Lipedema is a relatively common yet debilitating and often misdiagnosed lipodystrophy that mainly affects females. Very little is known about the etiology and pathophysiology of the disease. However, due to its high preference for female patients, hormonal factors may contribute to the pathogenesis., Case: A 62-year-old male patient presented to the authors with painful swelling of the thighs. The patient had been treated elsewhere for lymphedema with subsequent disease progression. Lipedema stage IV was confirmed by clinical examination and ultrasound. The patient underwent three sessions of tumescence liposuction which was well tolerated. Later on, the patient reported great improvement in terms of complaints as well as disfigurement., Conclusion: The etiology and pathophysiology of lipedema remain unclear. However, the case at hand shows that lipedema may, albeit rare, also present in male patients. Moreover, we show that liposuction is efficient and safe in treating lipedema even in atypical cases.

Introduction, Breast cancer-related lymphedema (BCRL) is a complication of treatment for breast cancer. The aim of the present study is to report a form of intensive treatment for BCRL., Method, A crossover study was conducted involving the evaluation of the change in the volume of the upper limbs of 45 women with BCRL who underwent the intensive Godoy Method® (eight hours/day for five days). Volumetric analyses were performed before and after treatment and differences were analyzed using the paired t-test. Reductions in volume were found in all patients., Results, The average reduction was 45.38%. The reduction was between 15% and 20% in 6.67% of the women (n = 3); 20% to 30% in 13.33% (n = 6); 30% to 40% in 20% (n = 9); 40% to 50% in 40% (n = 18); and more than 50% in 20% of the women (n = 9)., Conclusion, The intensive form of treatment for lymphedema is highly effective in a short period of time, with a 40% to 50% reduction in volume in five days, but requires specialized centers adapted to this form of therapy. This is an option for reference centers in the treatment of lymphedema and the formation of human resources.

The World Health Organization (WHO) has recognised obesity as one of the top ten threats to human health. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of an increased release of biologically active metabolites. Moreover, obesity predisposes the development of metabolic syndrome and increases the incidence of type 2 diabetes (T2DM), increases the risk of developing insulin resistance, atherosclerosis, ischemic heart disease, polycystic ovary syndrome, hypertension and cancer. The lymphatic system is a one-directional network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells that provides a unidirectional conduit to return filtered arterial and tissue metabolites towards the venous circulation. Recent studies have shown that obesity can markedly impair lymphatic function. Conversely, dysfunction in the lymphatic system may also be involved in the pathogenesis of obesity. This review highlights the important findings regarding obesity related to lymphatic system dysfunction, including clinical implications and experimental studies. Moreover, we present the role of biological factors in the pathophysiology of the lymphatic system and we propose the possibility of a therapy supporting the function of the lymphatic system in the course of obesity.

T helper cell responses are tailored to their respective antigens and adapted to their specific tissue microenvironment. While a great proportion of T cells acquire a resident identity, a significant proportion of T cells continue circulating, thus encountering changing microenvironmental signals during immune surveillance. One signal, which has previously been largely overlooked, is sodium chloride. It has been proposed to have potent effects on T cell responses in the context of autoimmune, allergic and infectious tissue inflammation in mouse models and humans. Sodium chloride is stringently regulated in the blood by the kidneys but displays differential deposition patterns in peripheral tissues. Sodium chloride accumulation might furthermore be regulated by dietary intake and thus by intentional behavior. Together, these results make sodium chloride an interesting but still controversial signal for immune modulation. Its downstream cellular activities represent a potential therapeutic target given its effects on T cell cytokine production. In this review article, we provide an overview and critical evaluation of the impact of this ionic signal on T helper cell polarization and T helper cell effector functions. In addition, the impact of sodium chloride from the tissue microenvironment is assessed for human health and disease and for its therapeutic potential.

Introduction: Cellulite is associated with variations in the skin appearance with cottage cheese, mattress-like, or orange peel. The most common areas for these lesions are the posterior or upper thighs and buttocks and mainly affect females after puberty. The objective of the study was to determine whether extracorporeal shock wave therapy (ESWT) or manual lymphatic drainage (MLD) is more effective for the reduction of the grade of cellulite after liposuction. Methods: This study is a single-blinded randomized controlled clinical trial. Thirty females with grade 3 cellulite were randomly distributed into two groups equal in number (n = 15), group A was equipped to ESWT and group B was equipped to MLD. The cellulite grading scale was used to assess cellulite grade, and the skinfold caliper was used to assess the thickness of subcutaneous fat. The assessment was carried out before and four weeks after starting the treatment. Both groups received topical retinol twice daily for four weeks; in addition, group A received ESWT, while group B received MLD, two times/week for 4 weeks. Results: The mean values of the skinfold caliper in group A decreased by 24.4% and in group B by 15.38% with a significant difference between the two groups (p < 0.001). Also, the mean values of the cellulite grading scale decreased significantly after treatment in group A compared with the mean values of group B (p < 0.001). Conclusions: There was more reduction in the grade of cellulite and thickness of subcutaneous fat in the ESWT group than the MLD group after liposuction.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.

Lipedema is a chronic, progressive disease that almost exclusively affects women and often misdiagnosed as obesity or primary lymphedema. Research concerning lipedema is sparse, and there is a lack of studies focusing on women's experiences of living with the illness. We interviewed fourteen women with lipedema with the aim of describing their experiences of living with lipedema. Our results show that women felt controlled by their body, and were fat-shamed and viewed by others as a person who lacked character. They received unsupportive advice on how to manage from healthcare, and blamed themselves while striving to take responsibility.

Patient: Female, 31-year-old, Final Diagnosis: Lipedema, Symptoms: Bruising • leg edema • leg pain, Medication: —, Clinical Procedure: —, Specialty: Endocrinology and Metabolic • Family Medicine • Medicine, General and Internal • Metabolic Disorders and Diabetics • Plastic Surgery • Psychiatry

Background Reduced diffusion along perivascular spaces in adults with Alzheimer’s-disease-related-dementias has been reported and attributed to reduced glymphatic flow. Objectives To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration. Methods 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 Tesla MRI. Diffusion-tensor-imaging (spatial resolution=2x2x2 mm; b-value=1000 s/mm2; directions=33) measures of diffusion (mm2/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (DTI-ALPS), were calculated. Regions were identified by a board-certified neuroradiologist from T1-weighted and T2-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score. Results The DTI-ALPS score was reduced in PD compared to ET participants (p=0.037). No association between DTI-ALPS score and MCI status, but an inverse association between DTI-ALPS and Fazekas score (p=0.002), was observed. DTI-ALPS scores were inversely associated with age (p=0.007). Conclusion Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.

The Western diet is rich in salt, and a high salt diet (HSD) is suspected to be a risk factor for cardiovascular diseases. It is now widely accepted that an experimental HSD can stimulate components of the immune system, potentially exacerbating certain autoimmune diseases, or alternatively, improving defenses against certain infections, such as cutaneous leishmaniasis. However, recent findings show that an experimental HSD may also aggravate other infections (e.g., pyelonephritis or systemic listeriosis). Here, we discuss the modulatory effects of a HSD on the microbiota, metabolic signaling, hormonal responses, local sodium concentrations, and their effects on various immune cell types in different tissues. We describe how these factors are integrated, resulting either in immune stimulation or suppression in various tissues and disease settings.

BackgroundLipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery.MethodsThis paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system.ResultsEighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested.ConclusionThese guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.

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Patient: Female, 41-year-old, Final Diagnosis: Malnutrition, Symptoms: Leg edema • weakness, Medication: —, Clinical Procedure: Lymphatic mapping, Specialty: Dermatology • Endocrinology and Metabolic • Surgery