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Background The mitofusin 2 (MFN2) R707W mutation causes debilitating human lipodystrophy featuring lower body adipose loss, upper body adipose hyperplasia, and dyslipidaemic insulin resistance. Mechanical complications include airway compromise due to head and neck adipose overgrowth. This condition, sometimes called Multiple Symmetrical Lipomatosis (MSL), is also seen in sporadic form strongly associated with excess ethanol consumption. Mitigating the cellular pathology, or, conversely, exacerbating it, inducing selective death of affected adipocytes, are potential therapeutic strategies. Methods Candidate exacerbating and mitigating approaches to MFN2-MSL were tested in human MFN2 R707W/R707W fibroblasts, and in Mfn2 R707W/R707W mice and derived preadipocytes. Cell survival, mitochondrial network morphology and integrated stress response markers were assessed in cells, and body composition and metabolic indices in mice. Results Forcing galactose metabolism in human MFN2 R707W/R707W dermal fibroblasts did not replicate the overt adipose mitochondrial phenotype. 50mmol ethanol had little effect on Mfn2 R707W/R707W white preadipocytes, but increased mitochondrial content and blunted mitolysosome formation in Mfn2 R707W/R707W brown preadipocytes. 20% EtOH consumption increased brown adipose tissue in female Mfn2 R707W/R707W mice , and serum lactate in males. Rapamycin – a candidate mitigating treatment - increased size and mitolysosome content of WT preadipocytes, and to a lesser degree of Mfn2 R707W/R707W preadipocytes. In male Mfn2 R707W/R707W mice, rapamycin reduced weight gain, brown adipose mass, and increased serum Fgf21. Finally, a panel of mitochondrial stressors solicited no selective death or ISR in Mfn2 R707W/R707W preadipocytes. Conclusions Ethanol mildly exacerbates murine MFN2 -related MSL, while rapamycin is tolerated. MFN2-related MSL may not be solely attributable to compromised oxidative phosphorylation.

Objective Evaluation of Multidimensional Clinical Outcomes Following Unilateral Biportal Endoscopic Unilateral Laminectomy for Bilateral Decompression (UBE-ULBD) for Symptomatic Lumbar Epidural Lipomatosis . Methods This retrospective study analyzed 15 consecutive patients with lumbar epidural lipomatosis (LEL) who underwent UBE-ULBD between February 2021 and November 2023. Demographic data, surgical techniques, radiographic parameters, and patient-reported outcomes were systematically reviewed. MRI was used to measure the Cross Sectional Area (CSA) of dural sac and paravertebral muscle to evaluate the decompression effect. The range of postoperative spinal canal decompression extent and facet joint preservation rate were evaluated by CT. Dynamic X-ray measurement of intervertebral mobility to assess lumbar stability. Visual Analogue Scale (VAS) was used to evaluate the relief degree of for low back/leg pain at preoperative and postoperative 1/3/6/12-month intervals. Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Scores (JOA) were used to evaluate the functional recovery. Fischgrund criteria were used to determine the global clinical efficacy grading. Group comparisons were performed using repeated-measures ANOVA and paired-samples t-tests. Categorical variables were presented as frequencies (percentages). Statistical significance was defined as P  < 0.05. Results All 15 patients successfully underwent UBE-ULBD, achieving complete removal of adipose tissue in the compressed segments. Each patient was followed for a minimum of 12 months postoperatively. Postoperative CSA of the dural sac was significantly larger than preoperative values ( p  < 0.001). The atrophy rate of the paraspinal muscles was 4.92%, and 77.78% of facet joints were preserved. No lumbar instability occurred during follow-up. VAS scores for low back and leg pain improved significantly from (7.37 ± 0.62) and (6.31 ± 0.38) preoperatively to (1.46 ± 0.20) and (1.49 ± 0.14) at 12 months postoperatively ( P  < 0.05). ODI scores improved significantly from (67.93 ± 2.40) preoperatively to (16.60 ± 2.06) at 1 year ( P  < 0.05). Similarly, JOA scores improved from (8.73 ± 1.94) to (25.93 ± 0.80) ( P  < 0.05). According to the Fischgrund criteria, 5 patients had excellent outcomes, 8 had good outcomes, 2 had fair outcomes, and the overall Good-to-excellent rate was 86.67%. One patient experienced incisional adipose tissue liquefaction with persistent drainage, which resolved after wound debridement and anti-inflammatory therapy. All patients were free of Complications such as cauda equina injury or cerebrospinal fluid leakage. Conclusion UBE-ULBD demonstrates excellent clinical and radiological outcomes in LEL patients, with minimal complications, making it an effective treatment option.

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

Objective: To present a case of gastroduodenal lipomatosis associated with familial multiple lipomatosis (FML). Clinical Presentation and Intervention: A 58-year-old male presented with FML that manifested as multiple, painless, subcutaneous lipomas on his body; his mother had subcutaneous lipoma without a diagnosis of gastroduodenal lipomatosis. His lipid profile was normal. Abdominal computed tomography showed multiple, submucosal, polypoid lesions (of uniform density) of fat in the stomach and duodenum, and a small, similar lesion in the ileum. Conclusion: This case shows that gastrointestinal lipomatosis can manifest as FML.

BackgroundMadelung disease is a rare lipid metabolic disorder, and most cases are sporadically reported. There are currently no systematic reviews summarizing the epidemiological and clinical characteristics of this disease. The purpose of the current article is to extract and analyze the existing evidence concerning Madelung disease derived from case series in order to provide adequate treatments for patients based on a more comprehensive understanding of the disease.MethodsPubMed, Embase, and Web of Science databases were queried for relevant articles using the search terms “Madelung disease,” “multiple symmetric lipomatosis,” “Launois-Bensaude syndrome” and synonyms until Aug 31,2020. Data statistics of Madelung disease epidemiology and clinical characteristics are summarized in different tables or charts with Microsoft Office software.ResultsPatients exhibiting Madelung disease were mostly located in Europe, although some records existed in Asia as well. Average patient age was between 45 and 65 years old. Type I was the most common form of the disease, and the neck was the most common location for tumors. Madelung disease is associated with various metabolic disorders, and hematoma and seroma were the most common complications. Overall recurrence rate was 18.3%, with similar recurrence rates after lipectomy and liposuction. Fewer complications occurred after liposuction compared with lipectomy, but relapse was more common after liposuction.ConclusionMadelung disease consists of specific epidemiological and clinical characteristics, knowledge of which can be helpful for diagnosis and cognition. Lipectomy and liposuction are considered to be the most effective treatment methods for Madelung disease; however, choice of surgery should be based on comprehensive consideration of the disease, such as severity, mass location, and patient expectations.Level of Evidence IVThis 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.

Lipomatosis of nerve is a rare malformation characterized by a fibrolipomatous proliferation within peripheral nerve. Lipomatosis of nerve most frequently involves the median nerve, and manifests clinically as a compressive neuropathy. However, 30–60% of cases are associated with tissue overgrowth within the affected nerve’s territory (e.g., macrodactyly for lipomatosis of nerve in the distal median nerve). Somatic activating PIK3CA mutations have been identified in peripheral nerve from patients with lipomatosis of nerve with type I macrodactyly, which is now classified as a PIK3CA-related overgrowth spectrum disorder. However, the PIK3CA mutation status of histologically confirmed lipomatosis of nerve, including cases involving proximal nerves, and cases without territory overgrowth, has not been determined. Fourteen histologically confirmed cases of lipomatosis of nerve involving the median ( N  = 6), brachial plexus ( N  = 1), ulnar ( N  = 3), plantar ( N  = 2), sciatic and superficial peroneal nerves ( N  = 1 each) were included. Ten cases had nerve territory overgrowth, ranging from macrodactyly to hemihypertrophy; and four cases had no territory overgrowth. Exome sequencing revealed “hotspot” activating PIK3CA missense mutations in 6/7 cases. Droplet digital polymerase chain reaction for the five most common PIK3CA mutations (p.H1047R, p.H1047L, p.E545K, p.E542K, and p.C420R) confirmed the exome results and identified an additional six cases with mutations (12/14 total). PIK3CA mutations were found in 8/10 cases with territory overgrowth ( N  = 7 p.H1047R and N  = 1 p.E545K), including two proximal nerve cases with extremity overgrowth, and 4/4 cases without territory overgrowth (p.H1047R and p.H1047L, N  = 2 each). The variant allele frequency of PIK3CA mutations (6–32%) did not correlate with the overgrowth phenotype. Three intraneural lipomas had no detected PIK3CA mutations. As PIK3CA mutations are frequent events in lipomatosis of nerve, irrespective of anatomic site or territory overgrowth, we propose that all phenotypic variants of this entity be classified within the PIK3CA-related overgrowth spectrum and termed “PIK3CA-related lipomatosis of nerve”.

Study Design: Narrative review of available literature. Objective: To summarize current trends in pathogenesis and management of spinal epidural lipomatosis (SEL) and suggest areas where more research would be of benefit. Methods: The available literature relevant to SEL was reviewed. PubMed, Medline, OVID, EMBASE, Cochrane, and Google Scholar were used to review the literature. Institutional review board approval is not applicable for this study. Results: This article clearly summarizes current trends in the pathogenesis and management of SEL. Conclusions: Possible etiologies of SEL include exogenous steroid use, endogenous steroid hormonal disease, obesity, surgery induced, and idiopathic disease. Comorbidities such as acquired immunodeficiency syndrome and Scheuermann’s disease have also been implicated in the pathogenesis of SEL. Steroid-induced SEL seems to have a proclivity for the thoracic region of the spine and has a higher incidence of paraplegia when compared with other forms. Several treatment modalities exist for SEL and are dictated by the underlying cause of the disorder. These include weight reduction, cessation of steroid medications, treatment of underlying endocrine abnormalities, and surgical decompression. Conservative treatments generally aim to decrease the thickness of adipose tissue in the epidural space, but the majority of patients tend to undergo surgical decompression to relieve neurologic symptoms. Surgical decompression provides a statistically significant reduction in symptoms, but postoperative mortality is high, influenced primarily by the patient’s preoperative comorbidities. Physicians should consider the underlying cause of SEL in a given patient before pursuing specific treatment modalities, but alarm symptoms, such as the development of acute cauda equina syndrome, should likely be treated with urgent surgical decompression.

Background Madelung’s disease (MD), alternatively referred to as benign symmetric lipomatosis, multiple symmetric lipomatosis, or Launois–Bensaude syndrome, is an uncommon benign disorder marked by symmetric proliferation of adipose tissue in the head, neck, and torso regions. Case description In this case, the patient was a female with the late middle-aged demographic, diagnosed with Type I MD. Notably, she exhibited no prior history of alcohol consumption, and there was no family history of MD. Subsequent to the clinical diagnosis, the patient underwent medical imaging assessments to delineate the surgical parameters. Post-surgery, she demonstrated a favorable recovery trajectory, marked by the absence of any surgical complications. Result The patient underwent successful surgical excision of the lipomatous mass. Postoperatively, she had an uneventful recovery with no complications and no recurrence observed during the follow-up period of seven months. Conclusion Timely diagnosis and early surgical intervention play a pivotal role in enhancing the quality of life for individuals with MD. Preoperative medical imaging examinations function as highly effective tools, contributing to heightened surgical safety and a decreased probability of encountering complications during the surgical procedure.

PurposeLumbar spinal epidural lipomatosis (LEL) is a condition characterized by excessive deposition of epidural fat in the spinal canal. Metabolic abnormalities may be associated with LEL, but few validated reports exist. Thus, we investigated the association between LEL and metabolic disorders in this study.MethodsA total of 218 patients who had neurological symptoms due to neural compression in the lumbar spinal canal were examined by magnetic resonance imaging (MRI), abdominal computed tomography (CT) scans and blood tests. We evaluated the epidural fat, dural sac and spinal canal areas using MRI, and the visceral fat and subcutaneous fat areas using abdominal CT. We compared the patients’ demographics and the radiological parameters between the LEL and non-LEL patients.ResultsThere were 58 LEL patients and 160 non-LEL patients. The LEL group included more men than women. In the MRI measurement, the dural sac area was similar between the LEL and non-LEL patients; however, the epidural fat/spinal canal ratio was much greater in the LEL group. In the LEL patients, factors associated with metabolic disorders, such as visceral fat area, uric acid (UA) and insulin levels, were significantly greater, compared to the non-LEL patients. In the logistic regression analysis, UA and visceral fat area were the independent explanatory factors in the pathogenesis of LEL.ConclusionsLEL patients had significantly more visceral fat and increased levels of insulin, UA and ferritin, which are closely related with metabolic disorders. This study indicates that the increased epidural fat in the spinal canal seen in the LEL patients is associated with metabolic syndrome.Graphical abstractThese slides can be retrieved under Electronic Supplementary material.

Background Facial infiltrating lipomatosis (FIL) is a congenital disorder that causes overgrowth of one side of the face. The purpose of this study was to determine whether PIK3CA mutations are present in tissues outside of the subcutaneous adipose. Methods FIL tissues from three patients were dissected to enrich for cells from skin, subcutaneous tissue, orbicularis oris muscle, buccal fat, zygomatic bone, and mucosal neuroma. Endothelial cells within the affected tissue also were enriched using CD31 microbeads. Laser capture microdissection on formalin-fixed paraffin-embedded histologic sections was performed to collect specific cell types. DNA was extracted from each tissue and cell type, and measured for the abundance of mutant PIK3CA alleles using droplet digital PCR. Results We detected mutant PIK3CA alleles in every tissue and cell type tested from each overgrown face; frequencies ranged from 1.5 to 53%. There were fewer mutant endothelial cells compared with nonendothelial cells, and the stromal cell compartment had the highest frequency of mutant cells in each tissue. Conclusions PIK3CA mutations are not restricted to a single tissue or cell type in FIL. Overgrowth in this condition is likely due to the mutation arising in a cell that contributes to several different facial structures during embryogenesis.