Subcutaneous Tissue Research Articles

Choke Anastomosis: A Key Element Acting as a Shunt Converter Between Adjacent Angiosomes.

Choke anastomosis is commonly recognized as a resistance factor that detrimentally affects the hemodynamics of the skin flap; however, its additional potential physiological roles in normal skin function are currently not fully understood. Ten cadaveric forehead flap specimens pedicled with unilateral STAs were perfused with lead oxide-gelatin mixture, and then dissected into 3 layers, including the super temporal fascia-frontalis-galea aponeurotica layer, the subcutaneous adipose tissue layer, and the "super-thin flap" layer. The forehead flap and stratified specimens underwent molybdenum target x-ray and subsequent transparent processing to effectively visualize the microscopic spatial architecture of arterial vessels across all levels. Based on the different anastomoses near the midline area of the flap, 2 types of arterial perfusion were identified: choke anastomosis type (8/10) and true anastomosis type (2/10). The former formed multiple choke anastomoses near the midline. In the "super-thin flap" layer, arterial perfusion density on the ipsilateral side was significantly higher compared to that on the contralateral side. The arterioles on the ipsilateral side exhibited a dense and uninterrupted distribution, whereas those on the contralateral side appeared sparse and dispersed. The latter exhibited an alternative perfusion pattern; the bilateral arterial vessels were connected with 3 to 5 true anastomoses near the midline. Furthermore, the microscopic architecture confirmed a uniform distribution of arterioles that remained continuous from ipsilateral to contralateral sides in the "super-thin flap" layer. This study demonstrated that choke anastomosis not only impairs blood perfusion in the adjacent angiosomes but also acts as a shunt converter to impact the blood supply of distal skin flaps at different levels through the "trans-territory diversion phenomenon." This results in necrosis of the superficial dermis while preserving survival of the deep subcutaneous adipose tissue.

Quantitative Optimization of Handheld Probe External Pressure on Dermatological Microvasculature Using Optical Coherence Tomography-Based Angiography.

Optical Coherence Tomography (OCT)-based angiography (OCTA) is a high-resolution, high-speed, and non-invasive imaging method that can provide vascular mapping of subcutaneous tissue up to approximately 2 mm. In dermatology applications of OCTA, handheld probes are always designed with a piece of transparent but solid contact window placed at the end of the probe to directly contact the skin for achieving better focusing between the light source and the tissue, reducing noise caused by minor movements. The pressure between the contact window and the skin is usually uncontrollable, and high external pressure affects the quality of microvascular imaging by compressing the vessels and obstructing the underlying blood flow. Therefore, it is necessary to determine a pressure range to ensure that the vessels can be fully imaged in high-quality images. In this paper, two pressure sensors were added to the existing handheld OCT probe, and the imaging probe was fixed to a metal stand and adjusted vertically to change the pressure between the probe and the tested skin site, a gradient of roughly 4 kPa (with 1-2 kPa error) increase was applied in each experiment, and the impact of pressure to the vessel was calculated. The experiment involved a total of five subjects, three areas of which were scanned (palm, back of the hand, and forearm). The vessel density was calculated to evaluate the impact of external pressure on angiography. In addition, PSNR was calculated to ensure that the quality of different tests was at a similar level. The angiography showed the highest density (about 10%) when the pressure between the contact window on the probe and the test area was between 3 and 5 kPa. As the pressure increased, the vascular density decreased, and the rate of decrease varied in different test areas. After fitting all the data points according to the different sites, the slope of the fitted line, i.e., the rate of decrease in density per unit value of pressure, was found to be 4.05% at the palm site, 6.93% at the back of the hand, and 4.55% at the forearm site. This experiment demonstrates that the pressure between the skin and contact window is a significant parameter that cannot be ignored. It is recommended that in future OCTA data collection processes and probe designs, the impact of pressure on the experiment be considered.

Lespedeza homoloba enhances the immunosuppressive milieu of adipose tissue and suppresses fasting blood glucose.

Immune cells migrate to hypertrophied adipocytes and release proinflammatory cytokines, leading to adipocyte dysfunction and diabetes. Numerous species of Lespedeza, which are members of the plant family Fabaceae and distributed primarily in temperate Asia and North America, exhibit binding to peroxisome proliferator-activated receptor (PPAR) γ, a target nuclear receptor for treating diabetes. Therefore, the present study aimed to determine which species of Lespedeza plants exert an anti-inflammatory effect in adipose tissue and suppression of blood glucose increase through PPARγ ligand and radical scavenging activity. PPARγ binding and DPPH radical scavenging assays of L. homoloba (LH), L. thunbergii (LT), L. maximowiczii (LM) and L. thunbergii (LT) were performed. LH and LT showed significant ligand activity towards PPARγ and notable radical scavenging activity. LH exhibited a stronger DPPH radical scavenging activity than LT and thus was measured adiponectin secretion from 3T3-L1-derived adipocytes and IL-10 secretion from murine splenocytes. LH increased the adiponectin and the IL-10 secretions. In flow cytometric analysis, BALB/c male mice administered LH exhibited an increase in regulatory T cells (Tregs) and cytotoxic T lymphocyte-associated protein (CTLA)-4+ Tregs as well as a decrease in T helper (Th)17, Th17/Treg ratio and CD8+ and CD4+ T cells in subcutaneous adipose tissue. Conversely, in the spleen, LH decreased Tregs and increased Th17 cells, Th17/Treg ratio and CD4+ and CD8+ T cells. These findings indicated that LH activated immunoreaction in the spleen and Treg cells that migrate to subcutaneous adipose tissue may suppress inflammation. In fasting blood glucose and adiponectin assays, LH-exposed mice exhibited suppression of fasting glucose levels. Therefore, LH may prevent type 2 diabetes by suppressing adipose tissue inflammation.

Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations.

Testosterone (T) and 17β-estradiol (E2) are produced in male and female humans and are potent metabolic regulators in both sexes. When E2 and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by E2 and T for metabolic function human females and males. In females, E2 is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T's conversion to E2 is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and E2 are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study.

Body composition between obstructive and non-obstructive bladder cancer: A retrospective study

Background: Body composition measurement during cancer follow-up would increase its role in improving nutritional status. Using a CT scan for nutritional evaluation with scheduled cancer screening or follow-up would add other useful information to help the physician gain a better understanding of the patient’s nutritional status, especially in adipose tissue. Objective: To evaluate the correlation of measured adipose tissue and skeletal muscle between obstructive and non-obstructive uropathy in bladder cancer on a CT scan. Background: Body composition measurement during cancer follow-up would increase its role in improving the nutritional status. Using a CT scan for nutritional evaluation with scheduled cancer screening or follow-up would add other useful information to help the physician gain a better understanding of the patient’s nutritional status, especially in adipose tissue. Objective: To compare the measured adipose tissue and the skeletal muscle between obstructive and non-obstructive uropathy in bladder cancer on a CT scan. Materials and Methods: A total of 69 patients, who underwent a CT scan of the abdomen including the pelvis before surgery and/or chemotherapy between January 2013 and December 2022, were enrolled. Analyses of the volume of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle tissue (SMT) calculated based on CT images were performed. Results: There was significantly lower VAT (p = 0.012) in the obstructive group than in the non-obstructive group. SAT, SMT, age, weight, height, BMI, and tumor size were not significantly different between both groups. Conclusion: In patients with bladder cancer, those with obstructive uropathy showed lower VAT than non-obstructive uropathy.

An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data.

F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging. We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022. In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only. FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.

Embryonic heat conditioning increases lipolytic gene expression in broiler chicks at day 4 post-hatch.

Exposure to elevated temperatures during incubation is known to induce epigenetic changes that are associated with immunological and stress-response differences at a later age. Reports on its effects on the adipose tissue are still scarce. In this experiment, we investigated the effect of embryonic heat conditioning (EHC) on growth, adipose tissue mRNA and global DNA methylation in broiler chicks at day 4 post-hatch. Fertile eggs were divided into two groups: control and EHC. Eggs in the control group were incubated at 37.8°C and 80% relative humidity from day 0 to day 18.5 (E0 to E18.5). The EHC eggs were subjected to an intermittent increase in temperature to 39.5°C and 80% relative humidity from E7 to E16 for 12h (07:30-19:30) per day. On day 4 post-hatch, control and EHC chicks were subjected to 36°C using three time points: 0 (no heat challenge serving as the control), and 2 and 12h relative to start of the heat challenge. Fifteen chicks were sampled from each group for every timepoint. Body weight was recorded before euthanasia and subcutaneous adipose tissue was collected. Body weights were similar in control and EHC groups. Diacylglycerol O-acyltransferase 2 (DGAT2) mRNA was lower in the EHC group at time 0 relative to control. Hormone-sensitive lipase (HSL) mRNA was greater in the EHC than control group at the 0h timepoint. Heat challenge affected adipose tissue DNA methylation, with methylation highest at 12h into the heat challenge. These findings highlight the dynamic molecular responses of chicks to heat stress during early post-hatch development and suggest that EHC may affect heat stress responses and adipose tissue development through mechanisms involving lipid remodeling and DNA methylation.

Use of Fresh Frozen Plasma in a Dramatic Case of ACE-Inhibitor Associated Angioedema

Angioedema describes a non-dependent, non-pitting and transient edema caused by the accumulation of vasoactive substances in the circulation. These vasoactive substances increase vascular permeability, causing swelling of the deep dermal, submucosal or subcutaneous tissues of the face, lips, neck, extremities or gastrointestinal tract. Urticaria may or may not accompany this condition. Angioedema is generally mediated through two pathways: histamine-mediated and bradykinin-mediated. Histamine-mediated angioedema generally responds to standard therapeutic measures (such as antihistamines, steroids and epinephrine), whereas bradykinin-mediated angioedema can be more difficult to manage in emergency departments (ED). Here, we present a patient who presented to our ED with bradykinin-mediated ACE-I-associated dramatic angioedema clinic, did not respond to standard treatments, rapidly improved with fresh frozen plasma (FFP) administration and was discharged after 6 days of follow-up in the emergency critical intensive care unit.

Correlation between fetal subcutaneous fat thickness and insulin resistance through cord blood analysis immediately after delivery

ObjectivesThis study aimed to determine whether fetal subcutaneous tissue (SCT) thickness, measured using ultrasound immediately before and after delivery, can reflect changes in glucose metabolism immediately after delivery. We also evaluated the impact of insulin resistance changes during pregnancy by comparing pregnant women with well-controlled gestational diabetes mellitus (GDM) and those with normal glucose metabolism. Study designThe study participants were 117 pregnant women, including 97 controls and 20 patients with GDM who visited our obstetric clinic between February and December 2022. The participants were scheduled for cesarean delivery at a gestational age of ≥37 weeks. SCT thickness before delivery was measured using ultrasound and within 48 h after delivery using Holtain calipers. The glucose and insulin concentrations were quantified from cord blood collected immediately after delivery. Based on these results, a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was performed to assess insulin resistance. Independent t-test or Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables were used to compare the various parameters. Correlations among the variables in each group were assessed by calculating the correlation coefficient (Pearson’s correlation). ResultsSCT thickness measured using ultrasound and calipers demonstrated a strong correlation where pregnant women with GDM exhibited thicker fetal SCT and neonate skinfolds than in those without GDM. Glucose and insulin levels in the cord blood were significantly elevated (p < 0.05) in the gestational diabetic group, along with remarkable differences (p < 0.001) in HOMA-IR. These variables indicated a higher prevalence of glucose intolerance in the neonates of mothers with GDM. In pregnant women with GDM, there was a statistically significant correlation between fetal abdominal SCT thickness and glucose levels (r = 0.64, p < 0.01) and HOMA-IR (r = 0.48, p < 0.05). ConclusionsMeasuring the subcutaneous fat thickness of the fetus shortly before delivery is beneficial for predicting insulin resistance in neonates. This is considered particularly useful for women with effectively managed GDM, where the presence of conditions such as macrosomia may not be pronounced.

Sorafenib safety evaluation: Real-world analysis of adverse events from the FAERS database

BackgroundSorafenib is approved for the targeted therapy of cancers such as liver cancer and renal cancer. Given its widespread use, drug-related adverse events have received attention, and the post-marketing regulatory link is crucial. ObjectiveBy using the FAERS database to mine the adverse events (AEs) related to sorafenib, comparing the association intensity of key AEs, and exploring potential drug-related AEs, it provides a reference for clinical medication. MethodsCollect ADE data related to sorafenib in the FAERS database from 2006 to 2023. Standardize the data, and map adverse events to system organ classes and preferred terms. Analyze using various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS. ResultsAmong 18,520 adverse event reports (AERs) where sorafenib was the primary suspected drug, a total of 390 preferred terms (PTs) of adverse reactions were identified, covering 24 different system organ classes (SOCs). Specifically, the adverse events of sorafenib mainly involve the digestive system, skin and subcutaneous tissue, as well as non-specific physical discomfort including infection and injury. Among them, digestive system symptoms and skin toxicity are typical adverse reactions of sorafenib. We also observed uncommon but clearly strong AE signals, such as chloracne (n = 3, ROR 1756.39, PRR 1756.32, IC 8.78, EBGM 439.83), low-differentiated thyroid cancer (n = 4, ROR 585.47, PRR 585.44, IC 8.2, EBGM 293.22). It is worth noting that palmar-plantar erythrodysaesthesia syndrome (n = 2109, ROR 73.98, PRR 72.03, IC 6.01, EBGM 64.25) and hepatic encephalopathy (n = 457, ROR 37.44, PRR 37.23, IC 5.13, EBGM 35.07) have a higher incidence and signal intensity. In addition, we also observed some adverse events not mentioned in the official drug instructions, such as vitamin K deficiency or increased protein induced by antagonist II (PIVKA-II), abnormal alpha-fetoprotein, tumor metastasis, and splenic atrophy. ConclusionSorafenib carries the risk of various adverse reactions while providing therapeutic effects. In clinical applications, physicians should closely monitor the occurrence of digestive system reactions, skin lesions, endocrine system lesions, as well as injuries, infections, and other events.

68 Abnormal Pathway of Bougie Via Subcutaneous Tissue Caused Surgical Emphysema in Difficult Intubation

68 Abnormal Pathway of Bougie Via Subcutaneous Tissue Caused Surgical Emphysema in Difficult Intubation

Risk analysis of enfortumab vedotin: A real-world approach based on the FAERS database

PurposeTo analyze the risk of enfortumab vedotin (EV), a targeted therapy for advanced bladder cancer, using real-world data from the U.S. Food and Drug Administration's Federal Adverse Event Reporting System (FAERS). MethodsA retrospective pharmacovigilance analysis was conducted using FAERS data from Q1 2020 to Q1 2024. Adverse drug events (ADEs) related to EV were identified and categorized according to the System Organ Classes (SOCs) and specific events. Statistical methods, such as the proportional reporting ratio, reporting odds ratio (ROR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean were used to detect safety signals. ResultsOf the 7,449,181 FAERS case reports, 1,617 EV-related ADEs were identified, including 101 preferred terms and 22 SOCs. The key SOCs included skin and subcutaneous tissue, metabolic, and nutritional disorders. Rare ADEs, such as lichenoid keratosis (n = 4; ROR 26.89), small intestinal perforation (n = 3; ROR 24.51), pigmentation disorder (n = 9; ROR 18.16), and cholangitis (n = 8; ROR 17.48), showed significant disproportionality. ConclusionWhile most findings aligned with the existing data, new signs such as lichenoid keratosis and small intestinal perforation were identified. Further studies are necessary to validate these findings and emphasize the need for the clinical monitoring of EV-related ADEs.

Chromoblastomycosis: A Single Centre Clinical Laboratory Experience of Seven Years (2016-2022) and Literature Review From Pakistan.

Chromoblastomycosis (CBM) is a chronic infection of skin and subcutaneous tissue. CBM cases have been reported in local literature from Pakistan with heterogenous demographic, diagnostic and therapeutic information. The objective of this study is to share the experience of CBM from a large tertiary care hospital laboratory in Pakistan. This was a retrospective observational study. Histopathology and microbiology data of suspected CBM between 2016 and 2022 was retrieved. Patients' demographics, site of involvement, histopathological findings and positive microbiology cultures were assessed. Literature search on Google Scholar, PubMed and PakMediNet was done between 1990 and 2023 with multiple terms. A total of 16 CBM cases were identified; 14 were histopathology positive and two were both histopathology and culture positive. The median age was 21 years, and 11 patients were male. The predominant site was lower extremities followed by the face. Severe acanthosis, hyperkeratosis and granuloma with sclerotic bodies were observed in all histopathology slides. Alternaria spp. and Phialophora spp. were isolated from two culture-positive cases. A total of nine cases of CBM were reported from Pakistan in PubMed non-indexed journal. CBM is not a commonly thought of disease when evaluating skin lesions in Pakistan. A high index of suspicion when assessing patients who may have a history of trauma, exposure to soil and suggestive lesions is reasonable. An integrated approach between clinicians, histopathologist and microbiologist is required to do early identification and therapeutic interventions.

Glutathione peroxidase 3 is essential for countering senescence in adipose remodelling by maintaining mitochondrial homeostasis

Adipose tissue senescence is a precursor to organismal aging and understanding adipose remodelling contributes to discovering novel anti-aging targets. Glutathione peroxidase 3 (GPx3), a critical endogenous antioxidant enzyme, is diminished in the subcutaneous adipose tissue (sWAT) with white adipose expansion. Based on the active role of the antioxidant system in counteracting aging, we investigated the involvement of GPx3 in adipose senescence. We determined that knockdown of GPx3 in adipose tissue by adeno-associated viruses impaired mitochondrial function in mice, increased susceptibility to obesity, and exacerbated adipose tissue senescence. Impairment of GPx3 may cause mitochondrial dysfunction through inner mitochondrial membrane disruption. Adipose reshaping management (cold stimulation and intermittent diet) counteracted the aging of tissues, with an increase in GPx3 expression. Overall metabolic improvement induced by cold stimulation was partially attenuated when GPx3 was depleted. GPx3 may be involved in adipose browning by interacting with UCP1, and GPx3 may be a limiting factor for intracellular reactive oxygen species (ROS) accumulation during stem cell browning. Collectively, these findings emphasise the importance of restoring the imbalanced redox state in adipose tissue to counteract aging and that GPx3 may be a potential target for maintaining mitochondrial homeostasis and longevity.

Changes in pancreatic steatosis by computed tomography 24 months after sleeve gastrectomy in youth with severe obesity

BackgroundPancreatic steatosis has been associated with obesity and the metabolic syndrome. Studies in adults have demonstrated improvement in pancreatic steatosis following sleeve gastrectomy (SG) with concomitant improvement in glucose homeostasis. ObjectivesTo examine changes in pancreatic steatosis in youth with severe obesity 24 months following SG. SettingAcademic hospital system. MethodsForty-seven youth (13–24 years) with severe obesity (37 females) were followed for 24 months; 23 had SG and 24 were nonsurgical (NS) controls. Attenuations of the pancreas and spleen were measured using computed tomography (CT) at baseline, 12- and 24-month follow-up. Subjects underwent magnetic resonance imaging (MRI) for subcutaneous and visceral adipose tissue (SAT, VAT), dual energy x-ray absorptiometry (DXA) for body composition, blood sampling for glycated hemoglobin (A1C), and fasting and postprandial insulin and glucose. Linear mixed effects (LMEs) models were used to compare within- and between-group changes over 24 months. ResultsAt baseline, SG had higher body mass index (BMI) versus NS (P = .033). Over 24 months, significant reductions were noted in weight, BMI, VAT, SAT, fat mass (FM), and lean mass (LM) in the SG versus NS groups (P ≤ .0001). There was a significant 24-month decrease in pancreatic steatosis in the SG group (P = .006). In the whole group, 24-month reductions in pancreatic steatosis correlated with BMI and FM decreases. No associations were found between pancreatic steatosis and glucose homeostasis parameters. ConclusionsPancreatic steatosis measured by CT improved after SG in youth. Further studies are needed to understand the relationship between pancreatic steatosis and glucose homeostasis.

Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics

BackgroundCancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx. MethodsSpatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx. ResultsDistinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs. ConclusionsThese findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.

Liver transplant recipients have worse metabolic body phenotype compared with matched non-transplant controls.

Quantification of body compartments, particularly the interaction between adipose tissue and skeletal muscle, is emerging as novel a biomarker of metabolic health. The present study evaluated the impact of liver transplant (LT) on body compartments. Totally 66 adult LT recipients were enrolled in whom body compartments including visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), muscle fat infiltration (MFI), fat-free muscle volume (FFMV), and liver fat (LF) were quantified via whole body magnetic resonance imaging (MRI). To provide non-LT comparison, each LT recipient was matched to at least 150 non-LT controls for same sex, age, and body mass index (BMI) from the UK Biobank registry. LT recipients (vs matched non-LT controls) had significantly higher subcutaneous (13.82 ± 5.47 vs 12.10 ± 5.10 L, P < 0.001) and visceral fat (7.59 ± 3.75 vs 6.72 ± 3.06 L, P = 0.003) and lower LF (5.88 ± 7.14 vs 8.75 ± 6.50%, P < 0.001) and muscle volume (11.69 ± 2.95 vs 12.12 ± 2.90 L, P = 0.027). In subgroup analysis, patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis (vs non-MASH cirrhosis) had higher ASAT, VAT, and MFI. A trend toward higher LF content was noted; however, this did not reach statistical significance (6.90 ± 7.35 vs 4.04 ± 6.23%, P = 0.189). Finally, compared with matched non-LT controls, patients transplanted for MASH cirrhosis had higher ASAT and VAT; however, FFMV and MFI were similar. Using non-LT controls, the current study established the higher-than-expected adiposity burden among LT recipients, which is even higher among patients transplanted for MASH cirrhosis. These findings provide data needed to design future studies developing radiomics-based risk-stratification strategies in LT recipients.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

737. ETHNIC, GENDER AND TUMOR-SPECIFIC ASSESSMENT OF BODY COMPOSITION IS CRITICAL FOR CLINICAL RELEVANCE IN PATIENTS UNDERGOING THERAPY FOR ESOPHAGEAL

Abstract Background Growing evidence has supported a role for body composition in predicting survival in patients undergoing esophagectomy. A contemporary meta-analysis of published data (n=44 studies) conducted for this study confirmed an association between reduced muscle mass at diagnosis and worse overall survival (HR 1.72, 95%CI 1.49-1.97). Variation in methods of assessing and defining parameters of body composition remain however an important barrier to the wider adoption in routine clinical practice. This is particularly pertinent in esophageal cancer due to known sex, biological and geographical difference in tumor subtypes. This study seeks to define baseline variation in body composition parameters and to report their association with 90-day and overall survival in a large international cohort of patients undergoing esophagectomy for cancer. Methods Patients who underwent esophagectomy in fourteen high-volume centers between January 2007 to December 2019 were eligible for inclusion. Survival data were included up until June 2022. Skeletal muscle, visceral and subcutaneous adipose tissues within CT images, acquired at the time of diagnosis, were analyzed in accordance with a standardized protocol. Results 1716 patients were recruited to this study from three global regions: North America (n=386;22.5%), Europe (n=940;54.8%) and Asia (n=390;22.7%). Patients were predominantly male (79.5%) and adenocarcinoma was the most common histological subtype (66.6%). Wide variation of skeletal muscle (17.1-83.5cm2), visceral adiposity (0.2-170.1cm2) and subcutaneous adiposity (0.2-216.8cm2) was observed at presentation. Characteristics significantly associated with levels of muscle and adiposity were global region, sex, age, and histological subtype (P&amp;lt;0.001) (Figure 1). Compared to adenocarcinoma, squamous cell carcinoma was associated with significantly lower levels of muscle and adiposity, a finding that was independent of global region, sex, and age using a multivariable linear regression model (p&amp;lt;.0001). Median follow-up was 71.3 (95%CI 69.1-73.5) months with a median overall survival of 60.9 (95%CI 53.0-68.9) months. Reduced skeletal muscle and an excess of total adiposity at the time of diagnosis was associated with worse 90-day mortality and long-term survival. An interactive online survival prediction tool was developed to provide personalized survival estimates based on relevant predictors including skeletal muscle, total adiposity at diagnosis and other tumor and patient specific variables. Conclusions This is the first and largest study to adopt standardized methods to define international variation in parameters of body composition in esophageal cancer patients. Findings corroborate the potential role of body composition as a method of prognostication in esophageal cancer and presents a on-line tool for convenient integration into clinical practice.

MM-535 Unusual Extramedullary Relapse in the Colon and Subcutaneous Tissue of a Patient With Multiple Myeloma

MM-535 Unusual Extramedullary Relapse in the Colon and Subcutaneous Tissue of a Patient With Multiple Myeloma