AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity.

BACKGROUND/OBJECTIVES: The incidence of obesity continues to increase worldwide and while the underlying pathogenesis remains largely unknown, nutrient excess, manifested by "Westernization" of the diet and reduced physical activity have been proposed as key contributing factors. Western-style diets, in addition to higher caloric load, are characterized by excess of advanced glycation end products (AGEs), which have been linked to the pathophysiology of obesity and related cardiometabolic disorders. AGEs can be "trapped" in adipose tissue, even in the absence of diabetes, in part due to higher expression of the receptor for AGEs (RAGE) and/or decreased detoxification by the endogenous glyoxalase (GLO) system, where they may promote insulin resistance. It is unknown whether the expression levels of genes linked to the RAGE axis, including AGER (the gene encoding RAGE), Diaphanous 1 (DIAPH1), the cytoplasmic domain binding partner of RAGE that contributes to RAGE signaling, and GLO1 are differentially regulated by the degree of obesity and/or how these relate to inflammatory and adipocyte markers and their metabolic consequences. SUBJECTS/METHODS: We sought to answer this question by analyzing gene expression patterns of markers of the AGE/RAGE/DIAPH1 signaling axis in abdominal subcutaneous (SAT) and omental (OAT) adipose tissue from obese and morbidly obese subjects. RESULTS: In SAT, but not OAT, expression of AGER was significantly correlated with that of DIAPH1 (n = 16; [Formula: see text], [0.260, 1.177]; q = 0.008) and GLO1 (n = 16; [Formula: see text], [0.364, 1.182]; q = 0.004). Furthermore, in SAT, but not OAT, regression analyses revealed that the expression pattern of genes in the AGE/RAGE/DIAPH1 axis is strongly and positively associated with that of inflammatory and adipogenic markers. Remarkably, particularly in SAT, not OAT, the expression of AGER positively and significantly correlated with HOMA-IR (n = 14; [Formula: see text], [0.338, 1.249]; q = 0.018). CONCLUSIONS: These observations suggest associations of the AGE/RAGE/DIAPH1 axis in the immunometabolic pathophysiology of obesity and insulin resistance, driven, at least in part, through expression and activity of this axis in SAT.

In severe obesity, subcutaneous adipose tissue cell-derived cytokines are early markers of impaired glucose tolerance and are modulated by quercetin.

BACKGROUND: Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. METHODS: Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. RESULTS: Serum levels of IL-9, IL-13, and MIP-1ß were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1ß and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. CONCLUSION: In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.

Marked loss of adipose tissue during neoadjuvant therapy as a predictor for poor prognosis in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: The influence of body composition changes during neoadjuvant treatment (NT) on long-term survival in patients with gastric cancer (GC) undergoing radical gastrectomy remains unclear. The present study aimed to explore the association between changes in body composition during NT and survival in patients with GC. METHODS: GC patients treated with NT and radical gastrectomy between 2015 and 2018 were included in this retrospective study. Skeletal muscle mass, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by computer tomography before and after NT. Body composition changes during NT were compared with Kaplan-Meier curves. Univariate and multivariate regression analyses were applied to determine the predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: In total, 157 GC patients were studied. A marked loss of adipose tissue was associated with poor nutritional status. The median follow-up time for all patients was 25 months. Patients with marked VAT loss (≥ 35.7%) during NT had significantly shorter OS (p = 0.028) and DFS (p = 0.03). Similarly, poorer OS (p = 0.033) and DFS (p = 0.003) were observed in patients with marked SAT loss (≥ 30.1%) during NT. Changes in skeletal muscle mass and body weight during NT were not associated with survival. Marked VAT loss accompanied by marked SAT loss was an independent predictor of OS (hazards ratio = 2.447; p = 0.045) and DFS (hazards ratio = 2.674; p = 0.018). CONCLUSIONS: Patients with locally advanced GC have a worse survival when they experienced marked loss of adipose tissue during NT.

Cardiovascular-related proteins and the abdominal visceral to subcutaneous adipose tissue ratio.

BACKGROUND AND AIMS: An increased amount of visceral adipose tissues has been related to atherosclerosis and future cardiovascular events. The present study aims to investigate how the abdominal fat distribution links to plasma levels of cardiovascular-related proteins. METHOD AND RESULTS: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 326, all aged 50 years), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue volumes were quantified by MRI. Eighty-six cardiovascular-related proteins were measured by the proximity extension assay (PEA). Similar investigations were carried out in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 400, all aged 75 years). In the discovery dataset (POEM), 10 proteins were related to the VAT/SAT-ratio using false discovery rate <.05. Of those, Cathepsin D (CTSD), Interleukin-1 receptor antagonist protein (IL-1RA) and Growth hormone (GH) (inversely) were related to the VAT/SAT-ratio in the validation in PIVUS following adjustment for sex, BMI, smoking, education level and exercise habits (p < 0.05). In a secondary analysis, a meta-analysis of the two samples suggested that 15 proteins could be linked to the VAT/SAT-ratio following adjustment as above and Bonferroni-correction of the p-value. CONCLUSION: Three cardiovascular-related proteins, cathepsin D, IL-1RA and growth hormone, were being associated with the distribution of abdominal adipose tissue using a discovery/validation approach. A meta-analysis of the two samples suggested that also a number of other cardiovascular-related proteins could be associated with an unfavorable abdominal fat distribution.

The Association of Periprostatic Fat and Grade Group Progression in Men with Localized Prostate Cancer on Active Surveillance.

PURPOSE: Evidence suggests that visceral fat quantity may be associated with post-prostatectomy outcomes and risk of prostate cancer related death. We evaluated whether increased fat volume, normalized to prostate size, is associated with decreased risk of disease progression. MATERIALS AND METHODS: Patients enrolled on a prospective active surveillance trial for at least 6 months who had magnetic resonance imaging within 2 years of enrollment were eligible. The surveillance protocol included a standardized followup regimen consisting of biennial prostate specific antigen and examination and yearly biopsy. Clinicopathological characteristics were collected at baseline. Three fat measurements were taken using prostate magnetic resonance imaging, including subcutaneous, linear periprostatic (pubic symphysis to prostate) and volumetrically defined periprostatic. Progression was defined as increase in Gleason grade group. Multivariable Cox proportional hazards models were used to evaluate fat volumes normalized by prostate size (stratified into tertiles). RESULTS: A total of 175 patients were included in the study. Average age was 62.5 years (SD 7.4) and average prostate specific antigen was 5.4 ng/dl (SD 3.9). Median followup was 42 months (IQR 18-60) and 50 patients (28.6%) had progression. Compared to the lowest tertile, the highest tertile of volumetric periprostatic fat measurement (HR 2.63, 95% CI 1.23-5.60, p=0.01) and linear periprostatic fat measurement (HR 2.30, 95% CI 1.01-5.22, p=0.05) were associated with worsened progression-free survival, while subcutaneous fat measurement (p=0.97) was not. Importantly, the model did not substantively change when accounting for patient body mass index and other factors. CONCLUSIONS: Increased periprostatic fat volume, normalized to prostate size, may be associated with shortened progression-free survival in men with prostate cancer on active surveillance.

Visceral adiposity is an independent risk factor for high intra-operative blood loss during living-donor liver transplantation; could preoperative rehabilitation and nutritional therapy mitigate that risk?

BACKGROUND & AIMS: Blood loss during liver transplantation (LT) is one of the major concerns of the transplant team, given the potential negative post-transplant outcomes related to it. Blood loss was reported to be higher in certain body compositions, such as obese patients, undergoing LT. Therefore, we aimed to study the risk factors for high blood loss (HBL) during adult living donor liver transplant (ALDLT) including the body composition markers; visceral-to-subcutaneous adipose tissue area ratio (VSR), skeletal muscle index and intramuscular adipose tissue content. In June 2015, an aggressive perioperative rehabilitation and nutritional therapy (APRNT) program was prescribed in our institute for the patients with abnormal body composition. METHODS: We retrospectively analyzed 394 patients who had undergone their first ALDLT between 2006 and 2019. Risk factors for HBL were analyzed in the total cohort. Differences in blood loss and risk factors were analyzed in relation to the APRNT. RESULTS: Multivariate risk factor analysis in the total cohort showed that a high VSR (odds ratio (OR): 1.98, 95% confidence interval (CI): 1.19-3.29, P = 0.009), was an independent risk factor for HBL during ALDLT, as well as a history of upper abdominal surgery, simultaneous splenectomy and the presence of a large amount of ascites. After the introduction of the APRNT, a significantly lower blood loss was observed during the ALDLT recipient operation (P = 0.003). Moreover, the significant difference in blood loss observed between normal and high VSR groups before the application of the APRNT (P < 0.001), was not observed with the APRNT (P = 0.85). Likewise, before the APRNT, only high VSR was a risk factor for HBL by multivariate analysis (OR: 2.34, CI: 1.33-4.09, P = 0.003). Whereas with the APRNT, high VSR was no longer a significant risk factor for HBL even by univariate analysis (OR: 0.89, CI: 0.26-3.12, P = 0.86). CONCLUSION: Increased visceral adiposity was an independent risk factor for high intraoperative blood loss during ALDLT recipient operation. With APRNT, high VSR was not associated with high blood loss. Therefore, APRNT might have mitigated the risk of high blood loss related to high visceral adiposity.

Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis.

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

The vacuum treatment for the pectus excavatum thickened subcutaneous fat of the chest wall and is effective in preteenagers.

PURPOSE: We report effects of treatment for pectus excavatum (PE) with a Vacuum Bell (VB). MATERIALS AND METHODS: Fifteen patients (13 males and 2 females) undergoing VB therapy over 6 years, aged 6-17 years (mean: 11.1 years), were divided into two Groups: Group 1 (G1), preteenagers (< 13 years); Group 2 (G2), teenagers (≧ 13 years). We retrospectively recorded changes in depth of depression and the Haller index. RESULTS: The depth of depression reduced in 93.3% of 15 patients (mean; 8.7 mm). Minimal change occurred in the Haller index but the subcutaneous fat thickened significantly (11/15 patients). The improvement rate on elevation of the chest wall was better in G1 than G2 (G1: 54.0% vs G2: 51.3%). CONCLUSION: The maximum depth of depression improved in PE patients as a result of thickening of subcutaneous fat. VB is most effective in preteenagers with PE.

The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development.

Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.

Insights Into the Pathophysiology of Cellulite: A Review.

BACKGROUND: The etiology of cellulite is unclear. Treatment of cellulite has targeted adipose tissue, dermis, and fibrous septae with varying degrees of success and durability of response. OBJECTIVE: Results from clinical trials that target different anatomical aspects of cellulite can provide insights into the underlying pathophysiology of cellulite. MATERIALS AND METHODS: A search of the PubMed database and ClinicalTrials.gov website was conducted to identify clinical trials that have investigated treatments for cellulite. RESULTS: A lack of trial protocol standardization, objective means for quantification of improvement and reported cellulite severity, and short-term follow-up, as well as variation in assessment methods have made comparisons among efficacy studies challenging. However, the lack of durable efficacy and inconsistency seen in clinical results suggest that dermal or adipose tissue changes are not the primary etiologies of cellulite. Clinical studies targeting the collagen-rich fibrous septae in cellulite dimples through mechanical, surgical, or enzymatic approaches suggest that targeting fibrous septae is the strategy most likely to provide durable improvement of skin topography and the appearance of cellulite. CONCLUSION: The etiology of cellulite has not been completely elucidated. However, there is compelling clinical evidence that fibrous septae play a central role in the pathophysiology of cellulite.

Changes in Muscle Quality and Body Composition 1 Year After Hand-Assisted Laparoscopic Donor Nephrectomy in Living Kidney Donors.

OBJECTIVES: Our aim was to investigate effects of surgery on living donors' body composition and clarify factors related to it. MATERIALS AND METHODS: We evaluated preoperative computed tomography images of 335 living kidney donors (127 men, 209 women) to calculate 3 body composition parameters and changes with aging by sex: (1) skeletal muscle mass, quantified by skeletal muscle index; (2) fat distribution, calculated by visceral adipose tissue/subcutaneous adipose tissue ratio; and (3) muscle quality, quantified by intramuscular adipose tissue content. Thereafter, with pre- and postoperative computed tomography images from 75 living kidney donors (25 men, 50 women) after hand-assisted laparoscopic donor nephrectomy, we compared pre- and postoperative body composition changes. RESULTS: Annual change in intramuscular adipose tissue content with age was 0.0049 in men and 0.0091 in women. Of 75 patients, 49 had lower quality of muscle, intramuscular adipose tissue content was significantly higher after nephrectomy (P < .001), and median change in intramuscular adipose tissue content was 0.061 (range, 0.018-0.11) in men and 0.052 (range, 0.017-0.18) in women. Univariate analysis revealed that skeletal mass index and visceral adipose tissue/subcutaneous adipose tissue ratio changes were significantly different between the intramuscular adipose tissue content improvement and deterioration groups. Multivariate analysis revealed skeletal mass index change was an independent factor for intramuscular adipose tissue content change (P = .0019). Intramuscular adipose tissue content change was negatively correlated with skeletal mass index change (r = -0.40). CONCLUSIONS: Although muscle quality deteriorates after nephrectomy, maintaining muscle mass is important to retaining muscle quality.

Testosterone is sequestered in dysfunctional adipose tissue, modifying androgen-responsive genes.

BACKGROUND/OBJECTIVE: The recognized association between male hypogonadism and obesity has multifactorial implications on adipose tissue (AT) physiology. The fat solubility of testosterone (T) suggests a sequestration process in fat depots, leading to reduced circulating levels of T in obesity. Several evidence suggest that steroids play a two-sided inhibitory role on adipogenesis by locally decreasing lipid accumulation and by stimulating lipolysis. The current study investigates T trafficking and activity in dysfunctional AT. SUBJECTS/METHODS: Samples of subcutaneous AT (SAT) were obtained from explants from lipoaspirate plastic surgery in six obese and six normal weight male patients. Experimental procedures on both SAT explants and insulin-resistant (IR) 3T3-L1 adipocytes were performed, including real-time PCR and mass-spectrometry quantification. RESULTS: A significant deregulation of gene responsiveness to androgens in IR cells and obese SAT was observed (all p < 0.05), together with reduced T release after adrenergic stimulation (-10% compared with -55% in lean SAT, p = 0.021). Higher concentrations of intracellular T and estradiol in obese SAT were also observed (2.4 vs. 1.3 ng/g, p = 0.013 and 0.075 vs. 0.22 ng/g, p = 0.004, respectively). Testosterone accumulation resulted in even lower expression in androgen-responsive genes involved in lipolytic and anti-adipogenic pathways from both in vitro and ex vivo experiments. CONCLUSIONS: These results suggest an altered response of dysfunctional fat cells to testosterone stimulation, which normally favors lipolysis and induces an anti-adipogenic effect. The considerable reduction of lipolytic T release after adrenergic stimulation in obese SAT contributes to AT dysfunction, in a feedforward loop further reducing T levels in obese hypogonadal males.

Abdominal visceral and subcutaneous adipose tissues in association with cardiometabolic risk in children and adolescents: the China Child and Adolescent Cardiovascular Health (CCACH) study.

Objective: To investigate the association of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in children and adolescents. Research design and methods: This cross-sectional study consisted of 8460 children and adolescents aged 6-18 years from Chinese urban areas who underwent dual-energy X-ray absorptiometry scan and had metabolic risk factors measured. Results: In multivariate analysis adjusted for region, family income, age, puberty development, physical activity, and smoking, VAT and SAT were significantly associated with all metabolic risk factors for both sexes (all p<0.01). After additional adjustment for fat mass index, most of these associations remain significantly positive. In boys, SAT had greater ORs for all risk factors compared with VAT; in girls, however, SAT had greater odds for high triglycerides, smaller odds for high low-density lipid cholesterol, and similar odds for other risk factors compared with VAT. In addition, boys had greater magnitude of associations of SAT with high total cholesterol, high low-density lipid cholesterol, and low high-density lipid cholesterol compared with girls; no sex differences for VAT were observed. Conclusions: Both abdominal VAT and SAT have adverse impacts on most of the cardiometabolic risk factors in youth. However, their relative contributions differ between sexes.

The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects.

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35-40 kg/m2] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m2) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1ß (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.

Adipose Tissue Distribution and Survival Among Women with Nonmetastatic Breast Cancer.

OBJECTIVE: Previous studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). METHODS: This study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1.2) months of diagnosis, covariates were collected from electronic health records, and vital status was assessed by death records. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression. RESULTS: SAT and VAT ranged from 19.0 to 891 cm2 and from 0.484 to 454 cm2 , respectively. SAT was related to increased risk of death (127-cm2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm2 increase; HR [95% CI]: 1.02 [0.91-1.14]). An association with VAT was noted among women with stage II cancer (stage II: HR: 1.17 [95% CI: 0.99-1.39]; stage III: HR: 0.90 [95% CI: 0.76-1.07]; P interaction < 0.01). Joint increases in SAT and VAT were associated with mortality above either alone (simultaneous 1-SD increase: HR 1.19 [95% CI: 1.05-1.34]). CONCLUSIONS: SAT may be an underappreciated risk factor for breast cancer-related death.

Painful Traumatic Neuromas in Subcutaneous Fat: Visibility and Morphologic Features With Ultrasound.

OBJECTIVES: Subcutaneous neuromas usually result from trauma and may lead to dissatisfaction in patients with a trigger point, loss of sensitivity in the relevant territory of innervation, and spontaneous neuropathic pain. Confirming clinically suspected cases of neuroma may prove difficult. The objective of this study was to evaluate the visibility and morphologic features of traumatic subcutaneous neuromas of the limbs with ultrasound (US). METHODS: Between January 2012 and August 2016, 38 consecutive patients clinically suspected of having subcutaneous neuromas were investigated with US. The diagnosis was confirmed on the basis of a focal morphologic abnormality of the nerve associated with trigger pain. Each neuroma was classified into 1 of 3 subtypes based on its injury pattern. The subtypes were terminal neuroma, spindle neuroma, and scar encasement, either isolated or associated with these subtypes. RESULTS: Forty-four lesions were found in the 38 patients, including 29 spindle neuromas (65.9%), 14 terminal neuromas (31.8%) and 1 scar encasement with no nerve caliber abnormality (2.3%). Fifteen neuromas (35% of all neuromas) were associated with scar encasement. In 13 cases that required surgery, the diagnosis of neuroma or scar encasement could be surgically proven and confirmed the validity of the US findings. CONCLUSIONS: Ultrasound can be used to show and classify subcutaneous nerves of the upper and lower limbs with high accuracy. The US trigger sign provides an indication of neuroma involvement in pain. This modality can play a substantial role both in the preoperative planning of neuroma surgery and in therapeutic US-guided procedures.

Function and Strength after Free Abdominally Based Breast Reconstruction: A 10-Year Follow-Up.

BACKGROUND: The long-term impact of abdominally based free flap breast reconstruction is incompletely understood. The aim of this study is to provide long-term, subjective and objective health data on abdominally based free flap breast reconstruction patients, with specific attention to the effects of laterality, flap type, and obesity. METHODS: Patients were enrolled in this prospective study between 2005 and 2010 and completed preoperative, early (<1 year), and long-term (5 to 10 years) evaluations. Objective examination included an assessment of upper and lower abdominal function and a functional independence measure. Patient-reported outcomes included the 36-Item Short-Form Health Survey and the BREAST-Q abdominal well-being module. Scores were compared by laterality (unilateral versus bilateral), flap type (muscle-sparing free transverse rectus abdominis musculocutaneous versus deep inferior epigastric artery perforator), and presence of obesity. RESULTS: Fifty-one patients were included, with an average 8.1-year follow-up. Overall, 78.8 percent of patients had stable or improved scores across the upper and lower abdominal function and functional independence measures, and minimal objective differences across flap laterality or types were observed. Postoperative scores improved for 36-Item Short-Form Health Survey physical health (p < 0.001) and mental health (p < 0.001), and did not differ based on laterality or flap type. Obesity negatively impacted physical health (p = 0.002) and mental health (p = 0.006). CONCLUSIONS: Abdominally based autologous breast reconstruction is associated with significant improvements in long-term quality of life across key domains of physical and mental health with little functional impairment and no long-term differences across flap type or laterality. Obese patients, however, may be at risk for subjective physical and mental health impairment, perhaps unrelated to the surgery itself.

Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB.

Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age and in several chronic disease states. The aim of this study was to determine the effects of human obese and lean subcutaneous adipose tissue secretome on myogenesis and metabolism in skeletal muscle cells derived from both young (18-30 yr) and elderly (>65 yr) individuals. Obese subcutaneous adipose tissue secretome impaired the myogenesis of old myoblasts but not young myoblasts. Resistin was prolifically secreted by obese subcutaneous adipose tissue and impaired myotube thickness and nuclear fusion by activation of the classical NFκB pathway. Depletion of resistin from obese adipose tissue secretome restored myogenesis. Inhibition of the classical NFκB pathway protected myoblasts from the detrimental effect of resistin on myogenesis. Resistin also promoted intramyocellular lipid accumulation in myotubes and altered myotube metabolism by enhancing fatty acid oxidation and increasing myotube respiration and ATP production. In conclusion, resistin derived from human obese subcutaneous adipose tissue impairs myogenesis of human skeletal muscle, particularly older muscle, and alters muscle metabolism in developing myotubes. These findings may have important implications for the maintenance of muscle mass in older people with chronic inflammatory conditions, or older people who are obese or overweight.