Mitochondrial Ca2+ signaling is a hallmark of specific adipose tissue-cancer crosstalk.

Obesity is associated with increased risk and worse prognosis of many tumours including those of the breast and of the esophagus. Adipokines released from the peritumoural adipose tissue promote the metastatic potential of cancer cells, suggesting the existence of a crosstalk between the adipose tissue and the surrounding tumour. Mitochondrial Ca2+ signaling contributes to the progression of carcinoma of different origins. However, whether adipocyte-derived factors modulate mitochondrial Ca2+ signaling in tumours is unknown. Here, we show that conditioned media derived from adipose tissue cultures (ADCM) enriched in precursor cells impinge on mitochondrial Ca2+ homeostasis of target cells. Moreover, in modulating mitochondrial Ca2+ responses, a univocal crosstalk exists between visceral adipose tissue-derived preadipocytes and esophageal cancer cells, and between subcutaneous adipose tissue-derived preadipocytes and triple-negative breast cancer cells. An unbiased metabolomic analysis of ADCM identified creatine and creatinine for their ability to modulate mitochondrial Ca2+ uptake, migration and proliferation of esophageal and breast tumour cells, respectively.

Discordant gene expression in subcutaneous adipose and skeletal muscle tissues in response to exercise training.

Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.

Sarcopenia and adipose tissue evaluation by artificial intelligence predicts the overall survival after TAVI.

Sarcopenia is a serious systemic disease that reduces overall survival. TAVI is selectively performed in patients with severe aortic stenosis who are not indicated for open cardiac surgery due to severe polymorbidity. Artificial intelligence-assisted body composition assessment from available CT scans appears to be a simple tool to stratify these patients into low and high risk based on future estimates of all-cause mortality. Within our study, the segmentation of preprocedural CT scans at the level of the lumbar third vertebra in patients undergoing TAVI was performed using a neural network (AutoMATiCA). The obtained parameters (area and density of skeletal muscles and intramuscular, visceral, and subcutaneous adipose tissue) were analyzed using Cox univariate and multivariable models for continuous and categorical variables to assess the relation of selected variables with all-cause mortality. 866 patients were included (median(interquartile range)): age 79.7 (74.9-83.3) years; BMI 28.9 (25.9-32.6) kg/m2. Survival analysis was performed on all automatically obtained parameters of muscle and fat density and area. Skeletal muscle index (SMI in cm2/m2), visceral (VAT in HU) and subcutaneous adipose tissue (SAT in HU) density predicted the all-cause mortality in patients after TAVI expressed as hazard ratio (HR) with 95% confidence interval (CI): SMI HR 0.986, 95% CI (0.975-0.996); VAT 1.015 (1.002-1.028) and SAT 1.014 (1.004-1.023), all p < 0.05. Automatic body composition assessment can estimate higher all-cause mortality risk in patients after TAVI, which may be useful in preoperative clinical reasoning and stratification of patients.

Effect of weight loss on knee joint synovitis over 48 months and mediation by subcutaneous fat around the knee: data from the Osteoarthritis Initiative.

BACKGROUND: Obesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression. METHODS: We included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (< ± 3% change, n = 117) over 48 months matched for age and sex. In magnetic resonance imaging (MRI) at baseline and 48 months, effusion-synovitis and Hoffa-synovitis using the MRI Osteoarthritis Knee Score (MOAKS) and average joint-adjacent SCF (ajSCF) were assessed. Odds-ratios (ORs) for synovitis progression over 48 months (≥ 1 score increase) were calculated in logistic regression models adjusting for age, sex, baseline BMI, Physical Activity Scale for the Elderly (PASE), and baseline SCF measurements. Mediation of the effect of weight loss on synovitis progression by local SCF change was assessed. RESULTS: Odds for effusion-synovitis progression decreased with weight loss and ajSCF decrease (odds ratio [OR] = 0.61 and 0.56 per standard deviation [SD] change, 95% confidence interval [CI] 0.44, 0.83 and 0.40, 0.79, p = 0.002 and 0.001, respectively), whereas odds for Hoffa-synovitis progression increased with weight loss and ajSCF decrease (OR = 1.47 and 1.48, CI 1.05, 2.04 and 1.02, 2.13, p = 0.024 and 0.038, respectively). AjSCF decrease mediated 39% of the effect of weight loss on effusion-synovitis progression. CONCLUSIONS: Effusion-synovitis progression was slowed by weight loss and decrease in local subcutaneous fat. Hoffa-synovitis characterized by fluid in the infrapatellar fat pad increased at the same time, suggesting a decreasing fat pad rather than active synovitis. Decrease in local subcutaneous fat partially mediated the systemic effect of weight loss on synovitis.

Distinct subpopulations of human subcutaneous adipose tissue precursor cells revealed by single-cell RNA sequencing.

Adipose-derived stem cells (ADSCs) play an important role in the differential capacity for excess energy storage between upper body abdominal (ABD) adipose tissue (AT) and lower body gluteofemoral (GF) AT. We cultured ADSCs from subcutaneous ABD AT and GF AT isolated from eight women with differential body fat distribution and performed single-cell RNA sequencing. Six populations of ADSCs were identified and segregated according to their anatomical origin. The three ADSC subpopulations in GF AT were characterized by strong cholesterol/fatty acid (FA) storage and proliferation signatures. The two ABD subpopulations, differentiated by higher expression of committed preadipocyte marker genes, were set apart by differential expression of extracellular matrix and ribosomal genes. The last population, identified in both depots, was similar to smooth muscle cells and when individually isolated and cultured in vitro they differentiated less than the other subpopulations. This work provides important insight into the use of ADSC as an in vitro model of adipogenesis and suggests that specific subpopulations of GF-ADSCs contribute to the more robust capacity for GF-AT to expand and grow compared with ABD-AT in women.NEW & NOTEWORTHY Identification of distinct subpopulations of adipose-derived stem cells (ADSCs) in upper body abdominal subcutaneous (ABD) and lower body gluteofemoral subcutaneous (GF) adipose tissue depots. In ABD-ADSCs, subpopulations are more committed to adipocyte lineage. GF-ADSC subpopulations are enriched for genes involved in lipids and cholesterol metabolism. Similar depot differences were found in stem cell population identified in freshly isolated stoma vascular fraction. The repertoire of ADSCs subpopulations was different in apple-shaped versus pear-shaped women.

Correlation between subcutaneous adipose tissue of the head and body mass index in children and young adults aged 8-19 years: implications for functional neuroimaging.

High body mass index (BMI) is presumed to signify high amounts of fat (subcutaneous adipose tissue) distributed across the body. High amounts of fat co-occurring with increased BMI has been cited as a potential neuroimaging barrier. Presence of increased fat may result in high electrical impedance and increased light diffusion-resulting in low signal to noise ratios during electroencepholography (EEG), functional near-infrared spectroscopy (fNIRS), and transcranial direct current stimulation (tDCS) measurements. Examining if subcutaneous fat in the head increases with respect to total body fat percentage and BMI in school-aged children and adolescents is an essential next step in developing possible mathematical corrections for neuroimaging modalities. We hypothesized that percentage of subcutaneous adipose tissue in the head region would increase with respect to both total body fat percentage and BMI. Increased subcutaneous head fat percentage was associated with a positive linear relationship with BMI and a quadratic relationship with total body fat. The data indicate that participant age, sex, and adiposity should be considered in the development of model corrections for neuroimaging signal processing in school-aged children and adolescents. Strength of regression coefficients in our models differed from those in adults, indicating that age-specific models should be utilized.

Intra- and inter-rater reliability of muscle and fat thickness measurements obtained using portable ultrasonography in older adults.

BACKGROUND & AIMS: Ultrasonography (US) is a promising tool for assessing body composition, offering accuracy and accessibility. However, technician skills and equipment characteristics can impact measurement reliability. We aimed to evaluate the intra- and inter-rater reliability of two evaluators using A-mode Portable Ultrasound to measure muscle and fat thickness in Brazilian older adults. METHODS: Quantitative cross-sectional study carried out with 150 community-dwelling older adults of Campinas-SP-Brazil, recruited in a retirement preparation program and a geriatric outpatient care unit. Scans of nine anatomical points were performed using the portable ultrasound in A-mode (BodyMetrix Pro System BX2000; Livermore, CA), with 6 scans per location and 3 measurements taken by each evaluator. After the selection and analysis of the generated images, muscle and fat thickness were measured. Reliability estimates between measures of the same evaluator (intra-rater) and between evaluators (inter-rater) were assessed using intraclass correlation coefficients (ICC), and differences within and between technicians were assessed using one-way ANOVA. Analyses were carried out for the overall sample and stratified by sex and by nutritional status. RESULTS: Excellent ICC values (>0.90) were found for subcutaneous fat thickness in intra- and inter-rater reliability analyses. The lowest ICC values were observed for deep abdominal fat thickness measured by evaluator 1 (ICC = 0.90) and evaluator 2 (ICC = 0.87), as well as in the inter-rater analysis (ICC = 0.85). Muscle thickness measurements had satisfactory ICC values for triceps, biceps, anterior thigh, and calf, ranging from moderate to good (ICC 0.50-0.90). CONCLUSION: A portable A-mode ultrasound demonstrates excellent reliability among both intra- and inter-raters for assessing fat thickness but only moderate for muscle thickness in older adults. Hence, this could prompt inquiries regarding the sole reliance on this tool for quantifying muscle mass and examining sarcopenia in older adults. To our knowledge, this study represents the first assessment of reliability for a portable A-mode ultrasound device conducted with older adults.

Subcutaneous fat necrosis of the newborn: A systematic review of surgical management and outcomes.

BACKGROUND: Subcutaneous fat necrosis of the newborn (SCFN) is a rare form of panniculitis manifesting as erythematous plaques or nodules at sites of brown fat in neonates. Surgical management may be indicated in severe cases; however, there is a paucity of literature compiling presentations and outcomes of these surgical patients. METHODS: The authors performed a systematic review, in consultation with a licensed librarian, on MEDLINE and Embase for studies including patients with SCFN who were surgically managed. RESULTS: The search strategy generated 705 results, among which 213 (30.2%) were excluded for lack of discussion on surgical management. Twenty-two studies discussed surgical management of SCFN in 26 patients, but in 6 of these studies the patients were not surgically managed. Ultimately, 16 articles with 16 patients who were surgically managed were included in the study. Average age at diagnosis was 11.8 ± 9.8 days; average age at surgery was 39.5 ± 70.4 days. The most common etiologies were "unknown" (6, 37.5%), therapeutic hypothermia (4, 25.0%), and birth complications (4, 25.0%). Patients harbored nodules on the back (14, 87.5%), upper extremities (7, 43.8%), lower extremities (7, 43.8%), buttocks (5, 31.3%), and head or neck (3, 18.8%). Linear regression models revealed the presence of back lesions and predicted concomitant medical complications (ß = 2.71, p = 0.021). CONCLUSIONS: Patients undergoing surgical management for SCFN most commonly harbor lesions on the back and extremities that are secondary to therapeutic hypothermia or of unknown origin. Reporting of additional cases is needed to further elucidate surgical management and outcomes.

Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience.

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear. METHODS: We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients. RESULTS: Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%. CONCLUSIONS: A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice.

Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages' engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

Observational Study on a Large Italian Population with Lipedema: Biochemical and Hormonal Profile, Anatomical and Clinical Evaluation, Self-Reported History.

We analyzed the medical condition of 360 women affected by lipedema of the lower limbs in stages 1, 2, and 3. The data were assessed for the whole population and compared between different clinical stages, distinguishing between obese and non-obese patients. The most frequent clinical signs were pain when pinching the skin, subcutaneous nodules, and patellar fat pads. The most frequently painful site of the lower limbs was the medial lower third of the thigh. The pain score obtained on lower limb points increased progressively with the clinical stage. In all points evaluated, the thickness of the subcutaneous tissue increased with the clinical stage. Analyzing the data on the lower medial third of the leg and considering only patients with type 3 lipedema, the difference between stages was statistically significant after correction for age and BMI. We found higher levels of C-reactive protein at more severe clinical stages, and the difference was significant after correction for age and BMI between the stages. Overall, the prevalence of alterations of glucose metabolism was 34%, with a progressive increase in prevalence with the clinical stage. The most frequent comorbidities were vitamin D insufficiency, chronic venous disease, allergies, dyslipidemia, headache, and depression of mood. Interestingly, in comparison with the general population, we found higher prevalence of chronic autoimmune thyroiditis and polycystic ovary syndrome. Finally, the clinical stage and the involvement of the upper limbs or obesity suggest a worse clinical, anthropometric, and endocrine-metabolic profile.

Comparison of Growth Performance, Carcass Properties, Fatty Acid Profile, and Genes Involved in Fat Metabolism in Nanyang and Landrace Pigs.

This study compared the growth, carcass properties, fatty acid profile, lipid-producing enzyme activity, and expression pattern of genes involved in fat metabolism in Nanyang and Landrace pigs. In the study, 32 Nanyang (22.16 ± 0.59 kg) and 32 Landrace barrows (21.37 ± 0.57 kg) were selected and divided into two groups, each with eight pens and four pigs per pen. The trial period lasted 90 days. The findings showed that the Nanyang pigs had lower average daily weight gain and lean percentage and higher average backfat thickness and lipogenic enzyme activities, including for acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase, than the Landrace pigs. A total of 14 long-chain fatty acids were detected using HPLC-MS, in which it was found that the levels of C14:0, C18:1n-9, C20:1n-9, C20:4n-6, and MUFA were up-regulated and C18:2n-6, C18:3n-3, PUFA n6, n3/n6, and total PUFA were down-regulated in the Nanyang pigs. Moreover, the mRNA levels for genes involved in fat metabolism, ME1, FAS, and LPL, were higher and the expression of SREBP1 mRNA was lower in the Nanyang pigs. Our results suggest genetic differences between the pig breeds in terms of growth, carcass traits, lipogenic enzyme activities, fatty acid profile, and the mRNA expression of genes involved in fat metabolism in subcutaneous fat tissue, which may provide a basis for high-quality pork production. Further studies are needed to investigate the regulation of lipid metabolism.

Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity.

OBJECTIVE: The objective of this study was to examine the hypothesis that abdominal and gluteal adipocyte turnover, lipid dynamics, and fibrogenesis are dysregulated among insulin-resistant (IR) compared with insulin-sensitive (IS) adolescents with obesity. METHODS: Seven IS and seven IR adolescents with obesity participated in a 3-h oral glucose tolerance test and a multi-section magnetic resonance imaging scan of the abdominal region to examine body fat distribution patterns and liver fat content. An 8-week 70% deuterated water (2 H2 O) labeling protocol examined adipocyte turnover, lipid dynamics, and fibrogenesis in vivo from biopsied abdominal and gluteal fat. RESULTS: Abdominal and gluteal subcutaneous adipose tissue (SAT) turnover rates of lipid components were similar among IS and IR adolescents with obesity. However, the insoluble collagen (type I, subunit α2) isoform measured from abdominal, but not gluteal, SAT was elevated in IR compared with IS individuals. In addition, abdominal insoluble collagen Iα2 was associated with ratios of visceral-to-total (visceral adipose tissue + SAT) abdominal fat and whole-body and adipose tissue insulin signaling, and it trended toward a positive association with liver fat content. CONCLUSIONS: Altered extracellular matrix dynamics, but not expandability, potentially decreases abdominal SAT lipid storage capacity, contributing to the pathophysiological pathways linking adipose tissue and whole-body IR with altered ectopic storage of lipids within the liver among IR adolescents with obesity.

Association between the Thickness of Lumbar Subcutaneous Fat Tissue and the Presence of Hernias in Adults with Persistent, Non-Traumatic Low Back Pain.

We aimed to analyze the association between the average lumbar subcutaneous fat tissue thickness (LSFTT) at each intervertebral level and the presence of hernias in patients with low back pain from an insurance network hospital in Mexico. This observational prospective study included 174 patients with non-traumatic lumbago who underwent magnetic resonance imaging with a 1.5T resonator. Two independent radiologists made the diagnosis, and a third specialist provided a quality vote when needed. The sample size was calculated with a 95% confidence interval using random order selection. Anonymized secondary information was used. Percentages and means with confidence intervals were tabulated. The area under the curve, specificity, and sensitivity of LSFTT were calculated. A regression analysis was performed to analyze the presence of hernias with LSFTT using each intervertebral level as a predictor. The odds of herniation at any intervertebral level increased directly with LSFTT. The average LSFTT predicted the overall presence of hernias; however, the LSFTT at each intervertebral level better predicted hernias for each intervertebral space. The area under the curve for LSFTT in predicting hernias was 68%. In conclusion, the average LSFTT was associated with the overall presence of hernias; patients with more hernias had higher LSFTT values.

Lipolytic agents for submental fat reduction: Review.

RESULT: The review delves into the realm of reducing submental fat, presenting a comprehensive analysis of various lipolytic agents used in plastic surgery and dermatology. The introduction establishes the context by defining the key indicators of a youthful neck and emphasizing the significant influence of fat in the aging process, particularly in the submental area. The usage of aminophylline involves subcutaneous injections, facilitating fat breakdown by increasing cyclic adenosine monophosphate and inhibiting adenosine receptors. Hypotonic pharmacologic lipo-dissolution induces fat dissolution via injected compounds under pressure, while lipolytic lymphatic drainage employs hyaluronidase to reduce tissue viscosity, aiding fat circulation. Glycerophosphorylcholine containing choline alfoscerate claims to activate fat metabolism, whereas the utilization of phosphatidylcholine combined with deoxycholate lacks cosmetic approval due to safety concerns. Deoxycholic acid has FDA approval for submental fat reduction, yet its mechanisms remain incompletely understood. Understanding the complex anatomy and mechanisms of lipolytic agents is essential for safe and effective submental fat reduction, despite evolving practices and off-label utilization. Clinical guidelines and references support this discussion, offering insights for safer applications.

A Family-Based Study of Inherited Genetic Risk in Lipedema.

Background: Lipedema is a progressive condition involving excessive deposition of subcutaneous adipose tissue, predominantly in the lower limbs, which severely compromises quality of life. Despite the impact of lipedema, its molecular and genetic bases are poorly understood, making diagnosis and treatment difficult. Historical evaluation of individuals with lipedema indicates a positive family history in 60%-80% of cases; however, genetic investigation of larger family cohorts is required. Here, we report the largest family-based sequencing study to date, aimed at identifying genetic changes that contribute to lipedema. Methods and Results: DNA samples from 31 individuals from 9 lipedema families were analyzed to reveal genetic variants predicted to alter protein function, yielding candidate variants in 469 genes. We did not identify any individual genes that contained likely disease-causing variants across all participating families. However, gene ontology analysis highlighted vasopressin receptor activity, microfibril binding, and patched binding as statistically significantly overrepresented categories for the set of candidate variants. Conclusions: Our study suggests that lipedema is not caused by a single exomic genetic factor, providing support for the hypothesis of genetic heterogeneity in the etiology of lipedema. As the largest study of its kind in the lipedema field, the results advance our understanding of the disease and provide a roadmap for future research aimed at improving the lives of those affected by lipedema.

Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

Association between increased Subcutaneous Adipose Tissue Radiodensity and cancer mortality: Automated computation, comparison of cancer types, gender, and scanner bias.

PURPOSE: Body composition analysis using computed tomography (CT) is proposed as a predictor of cancer mortality. An association between subcutaneous adipose tissue radiodensity (SATr) and cancer-specific mortality was established, while gender effects and equipment bias were estimated. METHODS: 7,475 CT studies were selected from 17 cohorts containing CT images of untreated cancer patients who underwent follow-up for a period of 2.1-118.8 months. SATr measures were collected from published data (n = 6,718) or calculated according to CT images using a deep-learning network (n = 757). The association between SATr and mortality was ascertained for each cohort and gender using the p-value from either logistic regression or ROC analysis. The Kruskal-Wallis test was used to analyze differences between gender distributions, and automatic segmentation was evaluated using the Dice score and five-point Likert quality scale. Gender effect, scanner bias and changes in the Hounsfield unit (HU) to detect hazards were also estimated. RESULTS: Higher SATr was associated with mortality in eight cancer types (p < 0.05). Automatic segmentation produced a score of 0.949 while the quality scale measurement was good to excellent. The extent of gender effect was 5.2 HU while the scanner bias was 10.3 HU. The minimum proposed HU change to detect a patient at risk of death was between 5.6 and 8.3 HU. CONCLUSIONS: CT imaging provides valuable assessments of body composition as part of the staging process for several cancer types, saving both time and cost. Gender specific scales and scanner bias adjustments should be carried out to successfully implement SATr measures in clinical practice.

Age-related changes in the fiber structure around adipocytes in the subcutaneous fat layer and their association with skin viscoelasticity.

OBJECTIVE: Age-related changes in the fiber structure around adipocytes were investigated via scanning electron microscopy (SEM) of excised skin tissues. In addition, the viscoelasticity of the subcutaneous fat layer was evaluated via elastography, and the association between the fiber structure and the viscoelastic properties was assessed. METHODS: Skin tissues excised from the facial cheek area were used. Then, SEM images of these tissues were obtained. The thickness and quantity of the fibers around adipocytes were assessed using a 5-point scale. The score was used to grade 18 tissue samples. Moreover, the viscoelasticity of the subcutaneous fat layer in the same samples was evaluated via ultrasound elastography. RESULTS: Based on the SEM image score, an association was observed between the fiber status score and age, thereby indicating a tendency toward age-related fibrosis. Fiber structures with high scores, which indicate fibrosis, had a significantly lower viscoelasticity based on ultrasound elastography. CONCLUSION: The thickness and quantity of fibrous structures around adipocytes in the subcutaneous fat layer increase with age, and these changes can be associated with decreased viscoelasticity in the subcutaneous fat layer.

Influence of subcutaneous adipose tissue index on prognosis in cirrhotic patients following endoscopic therapy: a retrospective cohort study.

BACKGROUND: The relation of adipose tissue depletion with prognostic outcome of variceal bleeding among cirrhotic patients is still inconclusive. The present work explored whether adipose tissue, which was measured based on computed tomography (CT), was valuable for analyzing rebleeding and mortality among patients with variceal bleeding who had undergone endoscopic therapy. METHODS: The study encompassed cirrhotic patients who underwent endoscopic therapy to prevent variceal rebleeding between January 2016 and October 2022. The L3-level CT images were obtained. Besides, impacts of subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), as well as total adipose tissue index (TATI) on rebleeding and mortality among cirrhotic patients following endoscopic therapy were examined. RESULTS: In this work, our median follow-up period was 31 months. Among those adipose tissue indexes, only SATI exhibited an independent relation to higher rebleeding (HR 0.981, 95% CI, 0.971-0.991, p < 0.001) and mortality (HR 0.965, 95% CI, 0.944-0.986, p = 0.001) risks. Upon multivariate Cox regression, low SATI (male < 30.15 cm2/m2, female < 39.82 cm2/m2) was independently linked to higher rebleeding risk (HR 2.511, 95% CI, 1.604-3.932, p < 0.001) and increased mortality risk (HR 3.422, 95% CI, 1.489-7.864, p = 0.004) after adjusting for other predictors. Furthermore, subgroups were created based on using nonselective ß-blockers (NSBBs), demonstrating that quantitatively assessing SATI exerts a vital role in evaluating rebleeding incidence in patients with or without NSBB therapy. CONCLUSION: This study underscores the potential of quantifying SATI as a means for achieving a more accurate risk classification for individual patients and identifying patients that can gain more benefits from nutritional intervention.