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Dendritic arborization is critical for the establishment and maintenance of precise neural circuits. Vascular endothelial growth factor D (VEGF-D), well-characterized as a “lymphangiogenic” growth factor, reportedly maintains dendritic arborization and synaptic strength in the hippocampus of adult mice through VEGF receptor (VEGFR-3) signaling. Here, we investigated the effect of chronic VEGFR-3-specific activation on adipose arbor morphometry using the Adipo-VD mouse, a model of inducible, adipose-specific VEGF-D overexpression. We examined whether adipose tissue innervation was preserved or functionally different in Adipo-VD mice during stress in vivo and if VEGFR-3 signaling afforded neuroprotection to challenged neurons in vitro. Chronic VEGFR-3 signaling in Adipo-VD subcutaneous adipose tissue resulted in a reduction in the dendrite length, dendritic terminal branches (filament length), dendritic terminal branch volume (filament volume), but increased dendrite branching. We also identified reduced stimulus-evoked excitatory sympathetic nerve activity in Adipo-VD mice. Following 6-hydroxydopamine (6-OHDA) denervation, Adipo-VD dendritic arbors were preserved, including improved dendritic branch volume, length, and dendritic branches than in wildtype tissues. In vitro, we found that chronic elevation of VEGFR-3 signaling in developing mVC neurons changes the dendritic arbor complexity and improves stress-induced structure remodeling. Developing neurons are conferred neuroprotection against stress, potentially by upregulation of proteolytic conversion of pro-BDNF to mature BDNF. Mature neurons, however, display improved dendritic arbor complexity, and unaltered dendritic structural remodeling and improved resistance to stress with VEGFR-3 signaling. Overall, chronically increasing VEGFR-3 signaling in neurons has a synergistic impact on neurosensitization and neuroprotection during stress.

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.

Introduction: Lipedema is an abnormal deposit of subcutaneous fat most often involving the lower limbs symmetrically. The physiopathology is poorly understood, but its peak of the almost exclusively female involvement and its peak of appearance at puberty, during pregnancy or at menopause orient toward a hormonal involvement, whereas other elements are in favor of a strong genetic predisposition. Klinefelter syndrome (KS) is a genetic disease linked to aneuploidy resulting in a karyotype 47 XXY most of the time. There is a substantial variation in clinical presentation, but it often features infertility, firm testicular hypotrophy, hypergonadotropic hypogonadism, gynecomastia, and learning difficulties. Many other pathologies are associated with KS, but lipedema is never mentioned and there are no data in the literature linking these two pathologies.

Lipedema is a chronic, progressive disease marked by abnormal fat distribution in the limbs, resulting in disproportionately sized and painful limbs. It primarily affects women and causes significant disability, functional impairment, and psychological distress. Despite its clinical significance in women’s health, lipedema is largely unknown, underdiagnosed, and misdiagnosed with other diseases with similar symptoms including obesity. It is difficult to distinguish between obesity and lipedema since these two conditions often coexist. Since the precise etiology of lipedema is yet to be determined, there is no treatment that targets the underlying cause. The most basic conservative treatment is decongestive physical therapy, which is normally needed life-long. In some cases, surgical procedures such as liposuction and excisional lipectomy are the therapeutic alternatives. Lipedematous scalp is a rare, dermatological condition with no known cause, characterized by increased subcutaneous tissue thickness and a smooth and boggy scalp. When it occurs in conjunction with alopecia, it is known as lipedematous alopecia, often mistaken as androgenetic alopecia. The goals of this article are to explain the etiology, clinical features, and treatment options for lipedema and lipedematous scalp (two relatively less known conditions), as well as to highlight their diagnostic features.

Introduction Lipoedema is a chronic and progressive fat distribution disorder characterised by a symmetrical disproportional increase of adipose tissue on the extremities. The disorder is most commonly associated with pain, oedemas, increased tendency of bruising, as well as sensory dysfunctions on the affected limbs, resulting in severely reduced quality of life (QoL) for exclusively female patients. According to current clinical guidelines, conservative treatment of lipoedema consists of manual lymphatic drainage, compression garments, or both combined as complex decongestive therapy (CDT). If conservative therapy does not result in sufficient improvement of symptoms, a surgical intervention, in the form of liposuction under tumescence anaesthesia, may be indicated. This systematic review aims to assess the clinical effectiveness and safety of liposuction in patients with lipoedema (stage I-III) in comparison to any conservative treatment, concerning patient-relevant outcomes, as reduction of pain, reduction in the size of extremities, improvement of QoL, and procedure-related adverse events. Methods A systematic literature search was conducted in December 2020 in five databases to answer customised research questions on clinical effectiveness and safety-related outcomes, yielding in overall 294 potentially relevant hits. One additional hit was identified by hand search. The study selection, data extraction, and assessment of the methodological quality of the studies were performed by two independent researchers. Results A total of six prospective and one retrospective single-arm before/after studies were eligible for inclusion in the current report. Overall, data on safety and clinical effectiveness were evaluated in 492 and 467 female patients of all three lipoedema stages, respectively. The post-operative follow-up ranged from six months to twelve years. Clinical effectiveness Due to the lack of controlled trials, no conclusions on the comparative clinical effectiveness of liposuction for lipoedema could be made. Therefore, data from the prospective single-arm studies comparing patient-reported complaints before and after the liposuction were analysed. All six prospective studies reported statistically significant improvements in pain outcomes pre- vs post-liposuction. These effects were reported beginning at a six-month follow-up but also up to twelve years after the intervention. Reduced sizes of patients’ extremities before-and-after liposuction were reported in three of the included studies, in terms of reduced leg volume and circumference of lower extremities. Statistically significant changes in lipoedema-related QoL outcomes were reported by four studies. Further, reduction in complaints about oedema/swelling, bruising and sensory dysfunctions were reported in some of the included studies.

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.

Williams syndrome (WS) is a relatively rare microdeletion disorder that occurs in as many as 1:7,500 individuals. WS arises due to the mispairing of low-copy DNA repetitive elements at meiosis. The deletion size is similar across most individuals with WS and leads to the loss of one copy of 25–27 genes on chromosome 7q11.23. The resulting unique disorder affects multiple systems, with cardinal features including but not limited to cardiovascular disease (characteristically stenosis of the great arteries and most notably supravalvar aortic stenosis), a distinctive craniofacial appearance, and a specific cognitive and behavioural profile that includes intellectual disability and hypersociability. Genotype–phenotype evidence is strongest for ELN, the gene encoding elastin, which is responsible for the vascular and connective tissue features of WS, and for the transcription factor genes GTF2I and GTF2IRD1, which are known to affect intellectual ability, social functioning and anxiety. Mounting evidence also ascribes phenotypic consequences to the deletion of BAZ1B, LIMK1, STX1A and MLXIPL, but more work is needed to understand the mechanism by which these deletions contribute to clinical outcomes. The age of diagnosis has fallen in regions of the world where technological advances, such as chromosomal microarray, enable clinicians to make the diagnosis of WS without formally suspecting it, allowing earlier intervention by medical and developmental specialists. Phenotypic variability is considerable for all cardinal features of WS but the specific sources of this variability remain unknown. Further investigation to identify the factors responsible for these differences may lead to mechanism-based rather than symptom-based therapies and should therefore be a high research priority.

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

This study examined the disease-specific quality of life (QoL) in lipoedema patients undergoing treatment for the condition with liposuction. We conducted a retrospective analysis of all patients (n = 69) who underwent liposuction for treatment of lipoedema between 2004 and 2019, and gathered data on patient age, body mass index, the number of liposuction sessions, and the amount of fat removed per side. The study also prospectively evaluated the QoL in 20 lipoedema patients before and after liposuction using the Freiburg Life Quality Assessment for lymphatic diseases questionnaire. The mean age was 50.6 ± 12.8 years, and the average number of liposuction sessions performed was 2.9 ± 1.9, with a mean volume of 1868 ± 885.5 mL of fat removed per side. Before treatment with liposuction, disease-specific QoL in patients with lipoedema was low on every single subscale as well as on the global score and showed a significant improvement in all aspects after liposuction. There was a significant correlation between a higher number of liposuction treatment sessions and general health status in lipoedema patients (P = .007). Liposuction greatly improves the QoL in lipoedema patients. A higher number of liposuction treatment sessions seem to have a positive effect on general health status in these patients.

Objective: The aim of this study is to investigate the effect of complex decongestive physiotherapy (CDP) plus intermittent pneumatic compression (IPC) applications on upper extremity circumference and volume in patients with lipedema. Methods and Results: All participants included in the study were included in a treatment protocol consisting of CDP and IPC. The Perometer 400 NT was used in the measurement of upper extremity volume and circumference before and after treatment. The measurements were performed in four reference points. According to the Perometer results before and after CDP, statistically significant reduction was found in the circumference of 3 of the 4 points of measurements performed in each of the left and right upper extremities. When the volume assessments were compared, it was seen that statistically significant reduction was found in the volume of both limbs. Conclusion: A treatment program consisting of CDP and IPC can be effective in reducing the circumference and volume of the arm in patients with upper extremity lipedema. So, CDP applications can help prevent the development of complications such as lipolymphedema, hypertension, and heart failure.

We report on a 29-year-old woman who presented with abdominal right upper quadrant pain after an outpatient liposuction procedure. A contrast-enhanced computed tomography scan revealed 4 hepatic perforation tracts with subcapsular liver hematoma and hematoperitoneum. The patient was treated by intravenous tranexamic acid and isotonic fluids and monitored on an intensive care unit. No intervention or surgery was necessary during her hospital stay. Follow-up imaging after 3 days using contrast-enhanced ultrasound still showed the perforation tracts in the liver but no expansion of subcapsular hematoma. After 7 days, the patient was discharged home with stable hemoglobin and reduced pain. Liver perforation is a rare complication of liposuction procedures. In patients with abdominal pain after liposuction, contrast-enhanced imaging studies should be performed to identify and characterize solid organ injury. Teams with expertise in angiography and visceral surgery need to be on standby.