Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema.

Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

High Volume Liposuction in Tumescence Anesthesia in Lipedema Patients: A Retrospective Analysis.

BACKGROUND: Lipedema is a chronic, progressive disease that occurs almost exclusively in women and leads to pathological, painful fat growths at the extremities. Only symptomatic therapy can be offered since the etiology of the disease has not yet been clarified. Liposuction in tumescent anesthesia has established itself as a surgical treatment method of choice. The complication rate associated with the procedure and the pharmacological course and safety of treatment in patients with lipedema has not yet been sufficiently studied. The aim of the study was to broaden the evidence on the safety of ambulatory high-volume liposuction in tumescent anesthesia in lipedema patients. Influencing factors of patients (weight, fat content, comorbidities) or the process technique (drug administration, volume of aspirates) should be investigated on the safety and risks of tumescent anesthesia. This was a retrospective data analysis in which data from 27 patients (40 liposuction procedures) treated at the Sandhofer and Barsch lipedema center between 2016 and 2018 were evaluated. The liposuctions were carried out in tumescent anesthesia and using a Power-Assisted Liposuction system. Clinical examinations and regular blood samples were carried out before the procedure, intra- and postoperatively. The procedures lasted an average of 118 minutes and an average of 6111 ml of aspirate was removed. For tumescent anesthesia, patients were given an average lidocaine dose of 34.23 mg/kg body weight and an epinephrine dose of 0.11 mg/kg body weight. No relevant complications associated with drug side effects, hypovolemia or hypervolemia or blood loss were detected. Liposuction under high volume tumescent anesthesia for the treatment of lipedema patients is, even for major intervention, a safe procedure. J Drugs Dermatol. 2021;20(3):326-334. doi:10.36849/JDD.5828.

SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema.

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles - but not cCMmiRNAs - were impacted by lipedema. Seven sEVmiRNAs (miR-16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR-144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

Prevention of Progression of Lipedema With Liposuction Using Tumescent Local Anesthesia: Results of an International Consensus Conference.

BACKGROUND: Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that usually affects the lower extremities of women. Also known as "two-body syndrome," the fat accumulations in lipedema are unsightly and painful. The disorder is well-known in Europe but is largely unrecognized and underdiagnosed in the United States. OBJECTIVE: To hold the First International Consensus Conference on Lipedema with the purpose of reviewing current European guidelines and the literature regarding the long-term benefits that have been reported to occur after lymph-sparing liposuction for lipedema using tumescent local anesthesia. METHODS: International experts on liposuction for lipedema were convened as part of the First International Congress on Lipedema in Vienna, Austria, June 9 to 10, 2017. RESULTS: Multiple studies from Germany have reported long-term benefits for as long as 8 years after liposuction for lipedema using tumescent local anesthesia. CONCLUSION: Lymph-sparing liposuction using tumescent local anesthesia is currently the only effective treatment for lipedema.

Fast Ablation of Anogenital Warts of the Urinary Meatus by Low-dose Ingenol Mebutate Gel.

Therapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate gel.