Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis.

Introduction: Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far. Methods: SAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies. Results: Lipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype. Conclusions: In summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.

[Settlement of the surgical treatment of lipoedema]. / Abrechnung der chirurgischen Therapie des Lipödems.

The billing of lipoedema treatment in Germany has come to be heterogeneous. This is due to the decision of the Federal Joint Committee ("Gemeinsamer Bundesausschuss", G-BA) to acknowledge lipoedema stage III as a treatment to be paid by the statutory health insurance funds ("Gesetzliche Krankenversicherung", GKV) until the completion of the trial study "LipLeg" at the end of 2024. Based on this decision, inpatient and outpatient surgical treatment of stage III lipoedema can be billed to the GKV, while the reimbursement of costs for surgical treatment of the other two stages remains a case-by-case decision of the GKV and is currently often rejected. Therefore, treatment costs are often paid by patients themselves. The question of the correct settlement of lipoedema treatment repeatedly arises in the context of legal disputes, which, in turn, repeatedly faces experts and courts with a major challenge. In the following article, the Task Force Lipoedema of the German Society for Plastic, Reconstructive and Aesthetic Surgery presents an overview of the various billing modalities and presents a proposal for the correct billing of lipoedema within the framework of the German medical fee schedule ("Gebührenordnung für Ärzte", GOÄ).

Free Flaps in Sternal Osteomyelitis After Median Sternotomy: A Center's 12-Year Experience.

BACKGROUND: Adequate treatment of deep sternal wound infections (DSWIs) after open thoracic surgery still presents a major challenge. This study retrospectively analyzes the results of a single center's 12-year experience in treating DSWI, with special emphasis on free flap reconstruction. METHODS: In this single-center, retrospective study, all patients admitted with the diagnosis of DSWI after open thoracic surgery between 2009 and 2020 were included. A comparative analysis was performed between: (1) pedicled versus free flaps, (2) the center's two workhorse flaps-the pedicled latissimus dorsi (pLD) versus free anterolateral thigh (fALT) flaps, as well as (3) myocutaneous (MC) versus fasciocutaneous (FC) flaps. Primary endpoints were length of hospital stay (LOS) after reconstruction and in-hospital mortality. RESULTS: Of a total of 165 patients included, 152 underwent DSWI defect reconstruction with a total of 12 different reconstruction methods. Although the defect size was larger in patients who underwent free flap coverage, and the risk profile in the fALT and FC flap groups was higher, the LOS after reconstruction (in days) did not differ significantly between the groups (pedicled vs. free flaps: 23 vs. 28, p > 0.05; pLD vs. fALT: 24.5 vs. 26, p > 0.05; MC vs. FC flaps: 23 vs. 26, p > 0.05). Also, no significant differences were found in terms of in-hospital mortality when comparing the groups (pedicled vs. free flaps: 11.2 vs. 17.4%, p > 0.05; pLD vs. fALT: 11.5 vs. 12.5%, p > 0.05; MC vs. FC flaps: 12.9 vs. 12.5%, p > 0.05). CONCLUSION: With proper patient selection, free tissue transfer is a valuable alternative in the treatment of sternal dehiscence after a DSWI. Furthermore, our data demonstrate that MC flaps are not necessarily superior to FC flaps in the reconstruction of sternal osteomyelitis defects.

Long-term Results After Autologous Fat Transfer for Treatment of Chronic Lower Extremity Wounds.

Autologous fat transfer may offer a simple and effective treatment option for chronic wound patients, delivering adipose-derived stem cells, with potent regenerative attributes. Nevertheless, the clinical benefit has not yet been sufficiently demonstrated. A total of 39 wound patients were treated with autologous fat transfer (AFT) and matched with a control group, according to the identified confounding variables "gender" and "method of defect closure." All data were acquired retrospectively. Primary outcome was "wound closure" and "reduction of wound size."After a follow-up of 48 weeks, there was no significant difference in primary outcome (wound closure P = .54) between both groups. The relative wound reduction after fat transfer was 69.9% ± 42.7% compared to 53.4% ± 106.8% in the control group (P = .91). Subgroup analysis of all patients, healed by secondary intention, revealed an increased wound size reduction (P = .03) and wound closure rate (P = .20) in the case group after 12 weeks. No adverse events were recorded. Fat grafting can reduce the wound size if left to secondary healing and may be considered individually for reconstructive purposes. A repeated application of autologous fat might be beneficial due to a temporary effect.

A 10-Year Retrospective before-and-after Study of Lipedema Surgery: Patient-Reported Lipedema-Associated Symptom Improvement after Multistage Liposuction.

BACKGROUND: Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. 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 disease-related complaints 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, 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 (p < 0.0001) and in stage I and II 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.

Autologous Lipofilling Improves Clinical Outcome in Patients With Symptomatic Dermal Scars Through Induction of a Pro-Regenerative Immune Response.

BACKGROUND: Autologous lipofilling is an emerging procedure to treat and possibly reverse dermal scars and to reduce scar-related pain, but its efficacy and mechanisms are poorly understood. OBJECTIVES: The aim of this study was to test the hypothesis that repeated lipografts reverse dermal scars by reinitiation of wound healing. METHODS: In a prospective, non-placebo-controlled clinical study, 27 adult patients with symptomatic scars were given 2 lipofilling treatments at 3-month intervals. As primary outcome, clinical effects were measured with the Patient and Observer Scar Assessment Scale (POSAS). Scar biopsies were taken before and after treatments to assess scar remodeling at a cellular level. RESULTS: Twenty patients completed the study. Patients' scars improved after lipofilling. The total POSAS scores (combined patient and observer scores) decreased from 73.2  [14.7] points (mean [standard deviation]) pretreatment to 46.1 [14.0] and 32.3 [13.2] points after the first and second lipofilling treatment, respectively. Patient POSAS scores decreased from 37.3 [8.8] points to 27.2 [11.3] and 21.1 [11.4] points, whereas observer POSAS scores decreased from 35.9 [9.5] points to 18.9 [6.0] and 11.3 [4.5] points after the first and second treatment, respectively. After each lipofilling treatment, T lymphocytes, mast cells, and M2 macrophages had invaded scar tissue and were associated with increased vascularization. In addition, the scar-associated epidermis showed an increase in epidermal cell proliferation to levels similar to that normal in skin. Moreover, lipofilling treatment caused normalization of the extracellular matrix organization towards that of normal skin. CONCLUSIONS: Autologous lipofilling improves the clinical outcome of dermal scars through the induction of a pro-regenerative immune response, increased vascularization, and epidermal proliferation and remodeling of scar tissue extracellular matrix.

Management of large volume liposuction in lipedema patients with von Willebrand disease: A systematic review and treatment algorithm.

BACKGROUND: When performing large volume liposuction, perioperative management of lipedema patients with coagulation disorders remains challenging due to a lack of clinical experience. With a prevalence of 1% of von Willebrand disease (VWD) in the general population, basic knowledge on diagnostic and adapted surgical strategies are essential for patients' safety. OBJECTIVE: Based on a selective literature review, the purpose of this article is to present a standardized algorithm for diagnosis and perioperative treatment of VWD patients undergoing large volume liposuction. METHODS: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term "(((liposuction) OR (surgery)) OR (lipectomy)) AND (((VWD) OR (hemostaseology)) OR (von Willebrand disease))". Included were articles published in English or German until November 2020. RESULTS: The evidence for large volume liposuctions in patients with VWD is limited. Experience is largely based on operations with similar bleeding risks. A safe performance requires an adjustment of the surgical technique and a customized perioperative drug substitution plan. According to the current literature, perioperative thromboembolic events appear to be rare with adequate drug treatment. CONCLUSION: The implementation of the developed diagnostic and treatment algorithm may help further reducing bleeding complications and improve the safety for treated patients.

Liposuction for Lipedema: Functional Therapy or Aesthetic Procedure?

Liposuction is one of the most common procedures undertaken in plastic surgery with a steadily increasing trend over the years. Although usually performed as an aesthetic procedure for body contouring, it can also be utilized in specific patient groups for disease symptom reduction. One such disease entity is lipedema. The goal of this video to present the authors' technique in the surgical treatment of lipedema, and to offer the viewer a better understanding of the differences between an aesthetic liposuction and a functional liposuction as performed on a lipedema patient. Between July 2009 and July 2019, 106 lipedema patients have been treated in the authors' specialized lipedema clinic, with a total of 298 liposuction procedures and a median follow-up of 20 months. The mean amount of lipoaspirate was 6354.73 ml (± 2796.72 ml). The patients reported a significant reduction in lipedema-associated complaints and improvement in quality of life. The need for conservative therapy was significantly reduced. No serious complications were reported. The authors also present before and after photographs of three patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Disease progression and comorbidities in lipedema patients: A 10-year retrospective analysis.

Multiple associated comorbidities have been described for lipedema patients. Disease diagnosis still remains challenging in many cases and is frequently delayed. The purpose of this study was to determine the most common comorbidities in lipedema patients and the impact of surgical treatment onto disease progression. A retrospective assessment of disease-related epidemiologic data was performed for patients who underwent liposuction between July 2009 and July 2019 in a specialized clinic for lipedema surgery. All patients received a standardized questionnaire regarding the clinical history and changes of lipedema-associated symptoms and comorbidities after surgery. 106 patients who underwent a total of 298 liposuction procedures were included in this study after returning the questionnaire fully filled-in. Multiple comorbidities were observed in the assessed collective. The prevalence for obesity, hypothyroidism, migraine, and depression were markedly increased in relation to comparable nonlipedema populations. Despite a median body mass index (BMI) of 31.6 kg/m2 (IQR 26.4-38.8), unexpected low prevalence of diabetes (5%) and dyslipidemia (7%) was found. Diagnosis and initiation of guideline-appropriate treatment were delayed by years in many patients. After surgical treatment (medium follow-up 20 months, IQR 11-42), a significant reduction of lipedema-associated symptoms was demonstrated. Lipedema occurs with a diversity of associated comorbidities. Therefore, on the basis of available data, the authors suggest the necessity of a multimodal therapy concept for a comprehensive and holistic treatment. Despite a commonly increased BMI, lipedema patients appear to have an advantageous metabolic risk profile.

Lipedema-Pathogenesis, Diagnosis, and Treatment Options.

BACKGROUND: Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. METHODS: This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library databases. RESULTS: The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diagnosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory healthinsurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. CONCLUSION: The diagnosis of lipedema remains a challenge because of the hetero - geneous presentation of the condition and the current lack of objective measuring instruments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.

Use of a Total Leg Fillet Flap to Cover Multiple Pelvic Pressure Ulcers.

The authors present the surgical strategy in the treatment of a morbidly obese paraplegic patient with a massive sacral pressure ulcer as well as bilateral trochanteric ulcers in a 1-step leg-sacrificing procedure utilizing the "spare-part" concept. It is the intention of the authors to reinforce the use of fillet flaps as a last resort option in paraplegic patients with pressure sores.

[Surgical treatment of lipoedema]. / Operative Behandlung des Lipödems.

Although liposuction of lipoedema is a well-established therapeutic option in plastic and reconstructive surgery, the commonly known operative protocols vary widely between clinics. A precise summary of all described protocols and a critical evaluation have not been published to date. This review aims to create a basic structure for future Standard Operative Protocols (SOPs) in the surgical treatment of lipoedema. For that purpose, 140 publications on therapeutic approaches concerning lipoedema have been reviewed and systematically categorized. The results indicate fundamental differences in treatment strategies as well as minor differences in organizational management.

Liposuction in the Treatment of Lipedema: A Longitudinal Study.

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.

A modified free muscle transfer technique to effectively treat chronic and persistent calcaneal osteomyelitis.

UNLABELLED: Successful management of chronic calcaneal osteomyelitis presents a major challenge for the plastic and reconstructive surgeon, especially in cases involving soft-tissue defects. This article describes a modified free muscle transfer technique to effectively eradicate chronic and persistent calcaneal osteomyelitis. METHODS: Between February 2009 and September 2009, 3 male patients with persistent calcaneal osteomyelitis were treated in our clinic. All 3 had purulent drainage for a minimum of 6 months and a maximum of 23 years. Multiple surgical debridements and vacuum-assisted closure had been used in the past, but the infection remained. We used a therapeutic protocol of repeated and radical surgical debridement with removal of nearly all cancellous bone and preservation of the cortical shell of the calcaneus. After the final debridement, the bone cavity was plugged by a free gracilis muscle flap from the contralateral side. A meshed split thickness skin graft was applied. Culture-specific antibiotics were administered for 2 weeks. RESULTS: All flaps healed uneventfully except for a minor hematoma that was treated conservatively. All 3 patients were able to return to ambulatory status with regular foot apparel. At last follow-up evaluation, they had no clinical, laboratory, or radiologic signs of osteomyelitis. CONCLUSION: This modified free muscle transfer technique seems to be successful in managing chronic and persistent calcaneal osteomyelitis. Infected and healthy cancellous bone of the calcaneus is removed to eradicate all possible foci that maintain inflammation. The resulting bony defect after the aggressive surgical debridement is sufficiently filled with a well-vascularized muscle that ensures a good wound healing. We consider this method to be a promising treatment option, which needs to be supported by further cases.

"The Maestro": a pioneering plastic surgeon--Sir Archibald McIndoe and his innovating work on patients with burn injury during World War II.

This article describes McIndoe's revolutionary methods of burn treatment and rehabilitation of patients with burn injury and outlines his personality traits that made him one of the most important plastic surgeons of the twentieth century. As a consultant plastic surgeon to the Royal Air Force, he set up a plastic surgery unit in the Queen Victoria Hospital in East Grinstead. By using biographical data and photography, McIndoe's work on burns treatment and the challenges he faced are presented. Before World War II, little was known about the treatment of severe burns and their complications, and even less was done about the rehabilitation and social reintegration of patients with burn injury. McIndoe changed all that by developing new techniques for the management and reconstruction of burn injuries. He helped his patients become and get accepted as a normal part of society again. The patients with burn injury treated by him formed the Guinea Pig Club. Sir Archibald Hector McIndoe, a charismatic plastic surgeon with an uncanny instinctive knowledge of psychology, recognized early that the rehabilitation of a burned patient was as important as the reconstruction of his physical body. His therapeutic approach to patients with burn injury was mental and physical.