Total Tissue Research Articles

Body Composition, Relative Dose Intensity, and Adverse Events among Patients with Colon Cancer.

Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events. We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures. Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38-0.81) for CT SMA; 0.56 (0.37-0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events. More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events. Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.

Assessment of longitudinal changes in body composition of children with lymphoma and rhabdomyosarcoma.

Studies examining changes in skeletal muscle and adipose tissue during treatment for cancer in children, adolescents, and young adults and their effect on the risk of chemotherapy toxicity (chemotoxicity) are limited. Among 78 patients with lymphoma (79.5%) and rhabdomyosarcoma (20.5%), changes were measured in skeletal muscle (skeletal muscle index [SMI]; skeletal muscle density [SMD]) and adipose tissue (height-adjusted total adipose tissue [hTAT]) between baseline and first subsequent computed tomography scans at the third lumbar vertebral level by using commercially available software. Body mass index (BMI; operationalized as a percentile [BMI%ile]) and body surface area (BSA) were examined at each time point. The association of changes in body composition with chemotoxicities was examined by using linear regression. The median age at cancer diagnosis of this cohort (62.8% male; 55.1% non-Hispanic White) was 12.7 years (2.5-21.1 years). The median time between scans was 48days (range, 8-207 days). By adjusting for demographics and disease characteristics, this study found that patients undergo a significant decline in SMD (β ± standard error [SE]=-4.1±1.4; p<.01). No significant changes in SMI (β ± SE=-0.5±1.0; p=.7), hTAT (β ± SE=5.5±3.9; p=.2), BMI% (β ± SE=4.1±4.8; p=.3), or BSA (β ± SE=-0.02±0.01; p=.3) were observed. Decline in SMD (per Hounsfield unit) was associated with a greater proportion of chemotherapy cycles with grade ≥3 nonhematologic toxicity (β ± SE=1.09±0.51; p=.04). This study shows that children, adolescents, and young adults with lymphoma and rhabdomyosarcoma undergo a decline in SMD early during treatment, which is associated with a risk of chemotoxicities. Future studies should focus on interventions designed at preventing the loss of muscle during treatment. We show that among children, adolescents, and young adults with lymphoma and rhabdomyosarcoma receiving chemotherapy, skeletal muscle density declines early during treatment. Additionally, a decline in skeletal muscle density is associated with a greater risk of nonhematologic chemotoxicities.

Sensitivity to thyroid hormone and risk of components of metabolic syndrome in a Chinese euthyroid population.

To evaluate the association of sensitivity to thyroid hormone with metabolic syndrome (MetS) and its components in a Chinese euthyroid population. A total of 3573 participants from Pinggu Metabolic Disease Study were analyzed. Serum-free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) area of abdominal, and lumbar skeletal muscle area (SMA) were measured. Central thyroid hormone resistance was calculated by the Thyroid Feedback Quantile-based Index (TFQI) and Chinese-referenced Parametric TFQI (PTFQI), Thyrotroph T4 Resistance Index (TT4RI) and TSH Index (TSHI). Peripheral thyroid hormone resistance was assessed by FT3/FT4 ratio. Higher values of TSHI (odds ratio [OR] = 1.167, 95% confidence interval [CI]: 1.079-1.262, p < .001), TT4RI (OR = 1.115, 95% CI: 1.031-1.206, p = .006), TFQI (OR = 1.196, 95% CI: 1.106-1.294, p < .001), PTFQI (OR = 1.194, 95% CI: 1.104-1.292, p < .001), and lower values of FT3/FT4 ratio (OR = 0.914, 95% CI: 0.845-0.990, p = .026) were associated with MetS. Increased levels of TFQI and PTFQI were associated with abdominal obesity, hypertriglyceridemia, and hypertension. Increased levels of TSHI and TT4RI were associated with hypertriglyceridemia, abdominal obesity, low high-density lipoprotein cholesterol. Reduced levels of FT3/FT4 ratio were associated with hyperglycemia, hypertension, and hypertriglyceridemia. The levels of TSHI, TFQI, and PTFQI were negatively related to SMA and positively related to VAT, SAT, and TAT (all p < .05). Reduced thyroid hormone sensitivity was associated with MetS and its components. Impaired thyroid hormone sensitivity might affect the distribution of adipose tissue and muscle.

Body composition assessment of people with overweight/obesity with a simplified magnetic resonance imaging method

To develop a simplified magnetic resonance imaging method (MRI) to assess total adipose tissue (AT) and adipose tissue free mass (ATFM) from three single MRI slices in people with overweight/obesity in order to implement body composition follow-up in a clinical research setting. Body composition of 310 participants (70 women and 240 men, age: 50.8 ± 10.6 years, BMI: 31.3 ± 5.6 kg.m−2) was assessed with 3 single slices (T6-T7, L4-L5 and at mid-thigh) MRI. Multiple regression analysis was used to develop equations predicting AT and ATFM from these three single slices. Then we implemented a longitudinal phase consisting in a 2-month exercise training program during which we tested the sensitivity of these equations in a subgroup of participants with overweight/obesity (n = 79) by comparing the exercise-induced variations between predicted and measured AT and ATFM. The following equations: total AT = − 12.74105 + (0.02919 × age) + (4.27634 × sex (M = 0, F = 1)) + (0.22008 × weight) + (26.92234 × AT T6-T7) + (23.70142 × AT L4-L5) + (37.94739 × AT mid-thigh) and total ATFM = − 33.10721 + (− 0.02363 × age) + (− 3.58052 × sex (M = 0, F = 1)) + (30.02252 × height) + (0.08549 × weight) + (11.36859 × ATFM T6-T7) + (27.82244 × ATFM L4-L5) + (58.62648 × ATFM mid-thigh) showed an excellent prediction (adjusted R2 = 97.2% and R2 = 92.5%; CCC = 0.986 and 0.962, respectively). There was no significant difference between predicted and measured methods regarding the AT variations (− 0.07 ± 2.02 kg, p = 0.70) and the ATFM variations (0.16 ± 2.41 kg, p = 0.49) induced by 2-months of exercise training. This simplified method allows a fully accurate assessment of the body composition of people with obesity in less than 20 min (10 min for images acquisition and analysis, respectively), useful for a follow-up.

Body composition predicts prognosis of hepatocellular carcinoma patients undergoing immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) with anti-PD-1/PD-L1 antibody are promising treatments for hepatocellular carcinoma (HCC), but lack reliable biomarkers of response. In the present study, we aimed to investigate the correlation between pre-treatment body composition measures (muscle, adipose, etc.) and the prognosis of patients with HCC treated with ICIs. We measured the total area of all skeletal muscles, total adipose tissue area, subcutaneous adipose tissue area, and visceral adipose tissue area at the level of the third lumbar vertebra using quantitative CT. Then, we calculated the skeletal muscle index, visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and total adipose tissue index. The Cox regression model was used to determine the independent factors of the patient prognosis and construct a nomogram to predict survival. The consistency index (C-index) and calibration curve were used to determine the predictive accuracy and discrimination ability of the nomogram. Multivariate analysis revealed that the SATI (high- vs. low SATI; HR 0.251; 95% CI 0.109-0.577; P = 0.001), sarcopenia (sarcopenia vs. no sarcopenia; HR 2.171; 95% CI 1.100-4.284; P = 0.026), and portal vein tumor thrombus (PVTT) (PVTT vs. No PVTT; HR 2.429; 95% CI 1. 197-4. 929; P = 0.014) were indicated as independent prognostic factors for OS in multivariate analysis. Multivariate analysis indicated that Child-Pugh class (HR 0.477, 95% CI 0.257-0.885, P = 0.019) and sarcopenia (HR 2.376, 95% CI 1.335-4.230, P = 0.003) were independent prognostic factors of PFS. We established a nomogram using SATI, SA, and PVTT to predict the 12-month and 18-month survival probability of HCC patients treated with ICIs. The C-index of the nomogram was 0.754 (95% CI 0.686-0.823), and the calibration curve confirmed that the predicted results were in good agreement with the actual observations. Subcutaneous adipose and sarcopenia are significant prognostic factors of patients with HCC receiving ICIs. A nomogram based on body composition parameters and clinical factors could well predict survival in HCC patients treated with ICIs.

Effects of effective antithyroid therapy on adiposity and skeletal muscle in patients with hyperthyroidism across gender and age groups.

The study aimed to evaluate the effects of effective antithyroid therapy on adiposity and skeletal muscle in patients with hyperthyroidism across gender and age groups. A total of 57 adult hyperthyroid patients (21 males and 36 females) who underwent effective antithyroid medication from January 2018 to January 2021 at Liuzhou People's Hospital and the First Affiliated Hospital of Guangxi Medical University were recruited and followed up for one year to observe the long-term efficacy of the antithyroid therapy. The eligible patients were divided by age and gender groups into male group A (males of <40 years old, n=12), female group A (females of <40 years old, n=19), male group B (males of 40-59 years old, n=8), female group B (female of 40-59 years old, n=13), and group C (patients of ≥60 years old, including one male and four females). A cohort of 57 healthy individuals was also recruited as controls. A Dual Energy X-ray (DXA) was performed to measure changes in fat and lean tissue mass and grip strength of the dominant hand before and after treatment and the body fat percentage (BFP). The whole-body skeletal muscle mass index (ASMI) was calculated to evaluate the long-term effects of antithyroid therapy. The eligible patients of all ages reported significantly increased total fat mass, body fat percentage, and body mass index (p<0.05). The total lean tissue mass was markedly increased in male and female group A (p<0.05), showed no significant changes in male and female group B (p>0.05), and exhibited a marked decline in group C (p<0.05). Significantly elevated ASMI after treatment was observed in male and female group A (p<0.05), while no significant changes were detected in ASMI after treatment in groups B and C (p>0.05). All patients in groups A and B exhibited enhanced grip strength, while the enhancement of grip strength in patients of group C was poor (p>0.05). Effective anti-hyperthyroidism therapy improves fat mass and body fat percentage in patients of all ages. However, gender and age differences exist in the effectiveness of improvements in total muscle mass and ASMI. Suboptimal muscle mass recovery was reported in patients over 40 years after effective anti-hyperthyroid therapy.

Comparative Evaluation of Recession Coverage Obtained Using the Pinhole Surgical Technique With and Without Platelet-Rich Fibrin: A Randomized Clinical Trial.

This randomized controlled clinical trial evaluated the pinhole surgical technique (PST) combined with platelet-rich fibrin (PRF) for the management of multiple recession defects compared to PST alone. Ten patients with 51 Miller Class I/ II or III gingival recessions were selected. Control sites were treated with PST alone, whereas test sites were treated with PST with PRF. Gingival recession depth (GRD), gingival recession width (GRW), probing depth (PD), clinical attachment level (CAL), keratinized tissue width (KTW), total soft tissue gain (TSTG), Plaque Index (PI), Gingival Index (GI), and gingival bleeding index (GBI) were measured at baseline and at 1, 3, and 6 months posttreatment. Both groups showed statistically significant root coverage. The mean recession coverage was 60.25% in the test group and 49.6% in the control group. The recession reduction from baseline was 2.50 mm for the test group and 1.88 mm for the control group. At the end of 6 months, all sites achieved adequate root coverage. PRF is a feasible alternative to connective tissue grafts as an adjunct to PST for the treatment of multiple recession defects.

Association of a lifestyle score with cardiometabolic markers among individuals with diabetes: a cross-sectional study

IntroductionTo investigate the associations of a lifestyle score with various cardiovascular risk markers, indicators for fatty liver disease as well as MRI-determined total, subcutaneous and visceral adipose tissue mass in...

In situ reconstruction of an infected infrarenal aortic pseudoaneurysm and arteriovenous fistula with self-made pericardium graft.

Infectious aortic disease is a challenging life-threatening disease in cardiovascular surgery. A 70-year-old man patient presented with an infected infrarenal aortic pseudoaneurysm and right iliac artery- left iliac vein fistula (arteriovenous fistula). He underwent total infected tissues excision, debridement, in situ reconstructions of the aorta using a self-made pericardium graft with omental coverage and arteriovenous fistula patch repair to prevent leakage. One-year follow-up revealed the absence of clinically relevant infection with patency of the graft and the absence of biochemical inflammatory markers.

More than skin-deep: visceral fat is strongly associated with disease activity, function and metabolic indices in psoriatic disease

ObjectiveTo compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement.MethodsBody composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively.ResultsThirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters—whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT—were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA.ConclusionsIn this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.

1257-P: Changes in Circulating Pancreatic Islet-Specific MicroRNA-375 Levels and Improvements in Insulin Sensitivity and Glucose Metabolism in Response to Weight-Loss Diets with Different Compositions of Macronutrients—The POUNDS Lost Trial

Pancreatic islet-specific microRNA-375 (miR-375) regulates insulin secretion and has an essential role in β-cell compensation when escalating insulin demand. We recently reported that changes in circulating miR-375 were associated with improved diabetogenic fat depots. Here, we investigated whether changes in circulating miR-375 induced by weight-loss diet interventions with different macronutrient intakes (fat, carbohydrate (carb), and protein) were related to improved insulin sensitivity and glucose metabolism. This study included participants from the POUNDS Lost trial with available data on circulating miR-375-3p at baseline (n=520) and its changes from baseline to 6 months after weight-loss diet interventions (n=508). At baseline, higher levels of miR-375 were related to lower degrees of BMI, total adipose tissue mass, and whole-body fat content (P &amp;lt;0.05 for all). There was a significant increase in miR-375 levels from baseline to 6 months (P by paired t-test &amp;lt;0.001). We found that associations of changes in miR-375 with changes in fasting insulin, glucose, and insulin resistance (HOMA-IR) were significantly modified by carb and fat intakes (P interaction &amp;lt;0.05 for all). In response to a low-fat and high-carb diet, a greater increase in miR-375 was significantly associated with larger reductions of fasting insulin and HOMA-IR at 6 months, regardless of baseline miR-375 levels. On the other hand, in response to a high-fat and low-carb diet intervention, there were significant positive associations between miR-375 changes and changes in glucose, insulin, and HOMA-IR. These results suggest that changes in the pancreatic islet-specific miRNA expression are associated with weight-loss diet intervention outcomes on insulin sensitivity and glucose metabolism. Different macronutrient intakes may modify these associations. Disclosure Y.Heianza: None. Q.Xue: None. H.Ma: None. G.Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F.Sacks: None. L.Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679)

Endotyping Difficult-to-Treat Chronic Rhinosinusitis with Nasal Polyps by Structured Histopathology

Introduction: This study aimed to identify the histopathologic characteristics associated with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNPs), enabling physicians to predict the risk of poor outcome after endoscopic sinus surgery (ESS). Methods: A prospective cohort study performed at the First Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018 with CRSwNP patients who underwent ESS. Polyp specimens were collected during surgery and were subjected to structured histopathological evaluation. Difficult-to-treat CRSwNPs were determined at 12–15 months post-operation according to the European Position Paper. Multiple logistic regression model was used to assess the association between histopathological parameters and the difficult-to-treat CRSwNP. Results: Among 174 subjects included in the analysis, 49 (28.2%) were classified with difficult-to-treat CRSwNP, which had higher numbers of total inflammatory cells, tissue eosinophils, and percentages of eosinophil aggregates and Charcot-Leyden crystals (CLC) formation but a lower number of interstitial glands than the nondifficult-to-treat CRSwNP. Inflammatory cell infiltration (adjusted OR: 1.017), tissue eosinophilia (adjusted OR: 1.005), eosinophil aggregation (adjusted OR: 3.536), and CLC formation (adjusted OR: 6.972) were independently associated with the difficult-to-treat outcome. Furthermore, patients with tissue eosinophil aggregation and CLC formation had an increasingly higher likelihood of uncontrolled disease versus those with tissue eosinophilia. Conclusion: The difficult-to-treat CRSwNP appears to be characterized by increased total inflammatory infiltrates, tissue eosinophilia, eosinophil aggregation, and CLC formation in structured histopathology.

#6332 INFLUENCE OF NUTRITIONAL STATUS ON THE INCREASE IN CARDIOVASCULAR RISK AND THE RISK OF KIDNEY DAMAGE IN COMORBIDITY OF HYPERTENSION AND COPD

Abstract Background and Aims It is widely known that obesity is a modulated additional factor in increasing cardiovascular risk in patients with hypertension. Since the number of patients with comorbidity of arterial hypertension and COPD is increasing, the question of the relationship between nutritional status and cardiovascular risk remains relevant. Purpose of the study: to determine the role of nutritional status indicators in the formation of cardiovascular risk in patients with comorbidity of hypertension and COPD. Method 101 patients were included in a cross-sectional study: 32 patients with comorbidity of hypertension and COPD (Gr I), 43 patients with hypertension (Gr II), and 26 patients with chronic obstructive pulmonary disease (Gr III). Exclusion criteria: informed consent of the patient to processing of personal data, Hypertension stage II, 1-3 degree, COPD A - C clinical groups(stable phase), age≥40 years. Exclusion criteria: age≥80 years, myocardial infarction and cerebral circulatory disorders, kidney diseases (polycystosis, developmental abnormalities, glomerulonephritis, pyelonephritis), diabetes mellitus, cancer, GFR &amp;lt; 30 ml/min. Patients underwent general clinical examination, determined nutritional status by anthropometric study and bioimpedancemetry, assessed the renal function by laboratory examination of blood. Methods of parametric and nonparametric statistics were used. Results A high cardiovascular risk in Gr I was in 22 (68,8%) patients, in Gr II - in 27 (62,9%) patients and in Gr III - in 10 (38,5%) patients. GFR in Gr I was 67,5 (57,0;77,0) ml/min, in Gr II -70.6 (57.0; 83.0) ml/min, and in Gr III - 82.5 (70.0;89.0) ml/min (p = 0.02). BMI in Gr I was 30.2 (26.5;35.0) kg/m2, in GrII - 29.7 (26.3;33.9) kg/m2, in GrIII - 26.8 (24.6;29.6) kg/m2. Percentage of adipose tissue in Gr I was 35.1 (30.0;41.7), in Gr II-38.2 (32.4;42.1) and in Gr III - 27.7 (21.0;34.1) (p = 0.01). The total muscle tissue in Gr I was 28,6 (24,6;30,6)%, in Gr II - 28,5 (25,0;31,2)%, in Gr III - 32,1 (27,8;35,3)%(p = 0.1), visceral fat in Gr I was 11,0 (8,0;14,0)%, in Gr II- 11,0 (9,0;15,0) %, in Gr III- 9,0 (6,0;13,0) %(p = 0.1); sarcopenia index in Gr I was 77,8(61,6;86,2), in Gr II- 77,8(66,1;101,8), in Gr III- 90,6(86,0;98,6)(p = 0,1). In Gr I, correlations were found: negative between GFR and high cardiovascular risk (R = -0.6), positive - between sarcopenia index, visceral fat and high cardiovascular risk (R = 0.5; 0.6), negative - between the amount of muscle tissue and high cardiovascular risk in patients (R = -0.5) (p&amp;lt;0,05). Conclusion In patients with a comorbidity of hypertension and COPD, along with an increase in the amount of adipose tissue and visceral fat, the amount of muscle tissue decreases, which leads to sarcopenic obesity. Sarcopenic obesity is associated with high cardiovascular risk and worsening of renal function, which also leads to an increased risk of cardiovascular complications.

Molecular Detection of Toxoplasma gondii, Neospora caninum and Encephalitozoon spp. in Vespertilionid Bats from Central Europe.

Bats may carry various viruses and bacteria which can be harmful to humans, but little is known about their role as a parasitic source with zoonotic potential. The aim of this study was to test wild bats for the presence of selected parasites: Toxoplasma gondii, Neospora caninum and microsporidia Encephalitozoon spp. In total, brain and small intestine tissues of 100 bats (52 Myotis myotis, 43 Nyctalus noctula and 5 Vespertilio murinus) were used for the DNA isolation and PCR detection of the abovementioned agents. Toxoplasma gondii DNA was detected by real-time PCR in 1% of bats (in one male of M. myotis), while all bats were negative for N. caninum DNA. Encephalitozoon spp. DNA was detected by nested PCR in 25% of bats, including three species (twenty-two M. myotis, two N. noctula and one V. murinus). Positive samples were sequenced and showed homology with the genotypes Encephalitozoon cuniculi II and Encephalitozoon hellem 2C. This is the first study on wild vespertilionid bats from Central Europe and worldwide, with a relatively high positivity of Encephalitozoon spp. detected in bats.

Adipose tissue is associated with kidney function parameters

Obesity is characterized by the accumulation of adipose tissue in different body compartments. Whether adipose tissue directly affects kidney function is still unknown. We aimed to investigate the role of the adipose tissue and circulating creatinine, cystatin C and kidney function in subjects free of cardio-renal diseases. In the KORA-MRI population-based study, 377 subjects (mean age 56.2 ± 9.2 years; 41.6% female) underwent whole-body 3T-MRI examination. Adipose tissue defined as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from T1-DIXON sequence using a semi-automatic algorithm. Serum creatinine and cystatin C were measured using standard laboratory and estimated glomerular filtration rate (e-GFR) was performed based on creatinine (e-GFRcrea), cystatin C (e-GFRcys) and creatinine-cystatin C (e-GFRcc). Linear regression analysis, adjusted for risk factors, was used to investigate the relationship between adipose tissue and circulating creatinine, cystatin C, and kidney function. In multivariate analyses VAT was inversely associated with eGFRcys (ß = − 4.88, p = < 0.001), and positively associated with serum cystatin C (ß = 0.05, p = < 0.001), respectively. No association was found between other adipose parameters such as total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) and serum creatinine, urine microalbumin and eGFRcrea. Stratified analyses according to BMI revealed confirmatory results for category of BMI > 30. VAT is positively associated with serum cystatin C and inversely with eGFR based on cystatin C, suggesting a direct involvement of visceral adipose tissue in increased metabolism of cystatin C and consequently decreased kidney function.

Single-cell and spatial transcriptomics to analyze radiation therapy-induced tumor microenvironment reshaping in HPV- cervical cancer.

e17528 Background: Radiotherapy (RT) is the most widely used conventional first-line treatment in cervical cancer (CC). However, the treatment response rate was only 10%-40%, and even lower in HPV- negative CC (HPV- CC). So far, previous knowledge of radiotherapy on tumor and tumor immune microenvironment (TME) remodeling is still insufficient. In this study, we aimed to comprehensively understand the dynamic change of tumor and TME of HPV- CC at the single-cell level. Methods: The single-cell and spatial transcriptome sequencing (STRNAseq) were used to analyze the TME of newly diagnosed HPV- CC tumor tissues, including pre-radiotherapy and 3 weeks after radiotherapy. Tissue samples were split into two parts, the freshly lysed single-cell suspension for 10X single-cell sequencing, and another part that was immediately processed into frozen and embedded for STRNAseq. Cell clustering, annotation and Single-cell sequencing and spatial transcriptome integration were analyzed by Seurat 4.0. The CNV of epithelial cells (ECs) was estimated by InferCNV. Results: A total of 14000 cells were obtained from paired HPV-CC patient samples (pre-RT and 3 weeks after RT) and clustered into 21 cell subsets. Six EC subsets, four fibroblast subsets, three macrophage subsets, two T cell subsets, two B cell subsets, one mast cell cluster, and an endothelial cell cluster were discovered. CNV analysis revealed that all ECs were malignantly proliferating tumor cells. Tumor cells accounted for 90% of the total tumor tissue prior to RT, but only less than 1% of tumor cells remain after RT. Fibroblasts and myeloid cells, which make up 60% of tumor tissue, increase significantly after radiotherapy, with myeloid cells accounting for nearly 50% of the total. Furthermore, we found a population of cells in the Post-RT sample that were both highly expressed CD14 and CD68 (macrophage biomarkers) and highly expressed COL1A2 (fibroblast biomarker). Differential analysis showed that this group of cells was down-regulated in Focal adhesion and ECM-receptor interaction pathways, while up-regulated in cytokine secretion and phagosome pathways, indicating that this group of cells might remodel the intercellular matrix and interacted with other cells to regulate the immune microenvironment. Integrating single-cell and spatial transcriptome data, fibroblasts and myeloid cells formed a tight co-distribution in tissues after radiotherapy, implying that their interaction is critical for the formation of the tumor immune microenvironment. Conclusions: This study comprehensively analyzed the dynamic change of tumor and TME of HPV- CC treated with RT at the single-cell transcriptional scale. After radiotherapy, fibroblasts and myeloid cells significantly increased and were highly heterogeneous, and the interaction between them is critical in forming a tumor ecosystem for radiotherapy.

Sedentary pattern, brain health, and cognitive function in rural‐dwelling older adults: A population‐based study

AbstractBackgroundSedentary behavior is distinct from low moderate‐to‐vigorous physical activity and is associated with a range of adverse health conditions. Population‐based studies have rarely examined the associations of objectively‐measured sedentary parameters, structural brain markers, and cognition among older adults.MethodsThis population‐based study included 2019 rural‐dwelling older adults (age ≥60 years, 59% women) who were free of dementia derived from MIND‐China baseline participants. In 2018‐2020, sedentary behavior parameters were measured using accelerometers. We used a neuropsychological test battery to assess global and domain‐specific cognitive function (memory, language, attention, and executive function). Volumes of total brain tissue, white matter hyperintensities, total grey matter, total white matter, ventricles, and hippocampus were assessed on the magnetic resonance imaging in a subsample (n = 1009). We used the general linear models, restricted cubic splines, and mediation models to examine the associations of sedentary parameters, structural brain markers, and cognitive measures, and the isotemporal substitution models to estimate associations of replacing sedentary time with physical activity.ResultsIn the total sample, adjusting for multiple confounders and MVPA, longer mean sedentary bout duration was linearly associated with lower z‐scores of global cognition, memory, and language, whereas the linear association of greater total sedentary time with poorer global cognition, memory, and language existed only among long‐sedentary individuals (&gt;10.2 hours/day); Having more breaks per sedentary hour or replacing 30‐minute sedentary time with the same amount of physical activity was significantly associated with higher cognitive z‐scores (P&lt;0.05). In the MRI subsample, simultaneously or separately entering multiple structural brain markers into the mediation models substantially attenuated the associations between mean sedentary bout duration and cognitive z‐scores.ConclusionIn the rural‐dwelling Chinese older adults, the association of prolonged uninterrupted sedentary time with poor cognition is largely mediated by structural brain markers and frequent breaks in sedentary time are associated with brain health.

Immune modulation through secretory autophagy.

Autophagy is a central mechanism of cellular homeostasis through the degradation of a wide range of cellular constituents. However, recent evidence suggests that autophagy actively provides information to neighboring cells via a process called secretory autophagy. Secretory autophagy couples the autophagy machinery to the secretion of cellular content via extracellular vesicles (EVs). EVs carry a variety of cargo, that reflect the pathophysiological state of the originating cells and have the potential to change the functional profile of recipient cells, to modulate cell biology. The immune system has evolved to maintain local and systemic homeostasis. It is able to sense a wide array of molecules signaling disturbed homeostasis, including EVs and their content. In this review, we explore the emerging concept of secretory autophagy as a means to communicate cellular, and in total tissue pathophysiological states to the immune system to initiate the restoration of tissue homeostasis. Understanding how autophagy mediates the secretion of immunogenic factors may hold great potential for therapeutic intervention.

Investigation into the content of red material in EUS-guided pancreatic cancer biopsies.

The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P= .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74mm2 and 10.74mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P< .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] μg vs .70 [interquartile range, .27-1.24] μg; P< .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ= .66, P< .001). In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.

Risk Factors and Complications in Reduction Mammaplasty: A Systematic Review and Meta-analysis.

Reduction mammaplasty (RM) has become established as the standard effective method for treating macromastia, but reports on the risk factors that predispose to postoperative complications have been conflicting. This meta-analysis aimed to pool the available data to identify predictors of complications following RM. The PubMed, Web of Science, Embase, and Cochrane databases were screened from inception to 1 Jan 2022, and studies were included based on predefined criteria. The perioperative risk factors BMI, smoking, age, diabetes, radiation therapy, and tissue resection weight were extracted and their correlation with complications assessed. A total of 40 studies comprising of 5908 patients were included. BMI ≥ 30kg/m2 (OR = 1.65, 95% CI 1.35-2.02; p < 0.01) and ≥ 40kg/m2 (OR = 1.97, 95% CI 1.26-3.08; p < 0.01), smoking (OR = 2.57, 95% CI 2.01-3.28; p < 0.01), diabetes (OR = 2.21, 95% CI 1.19-4.07; p < 0.05), a unilateral resection weight ≥ 1000g (OR = 1.76, 95% CI 1.02-3.05; p < 0.05), and radiation therapy (OR = 11.11, 95% CI 2.01-3.28; p < 0.01) were associated with higher rates of postoperative complications. Obese patients (BMI ≥ 30kg/m2) were more likely to experience fat necrosis (OR = 3.00, 95% CI 1.37-6.57; p < 0.01) and infection (OR = 1.66, 95% CI 1.15-2.40; p < 0.05). Smokers had a 2.03 times higher risk of infection (95% CI 1.24-3.31; p < 0.01) and 2.34 times higher risk of dehiscence (95% CI 1.38-3.98; p < 0.01). No association between complication occurrence and age 40 or 50 years or total tissue resection weight ≥ 1000g was identified. This meta-analysis provides evidence that obesity, smoking, diabetes, unilateral resection weight ≥ 1000g, and preoperative radiation therapy predispose to complication occurrence in RM. This information can optimize the ability of surgeons to provide preoperative patient education, perioperative assessment, and postoperative care planning. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .