Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments.

During weight loss, reductions in body mass are commonly described using molecular body components (eg, fat mass and fat-free mass [FFM]) or tissues and organs (eg, adipose tissue and skeletal muscle). While often conflated, distinctions between body components established by different levels of the 5-level model of body composition-which partitions body mass according to the atomic, molecular, cellular, tissue/organ, or whole-body level-are essential to recall when interpreting the composition of weight loss. A contemporary area of clinical and research interest that demonstrates the importance of these concepts is the discussion surrounding body composition changes with glucagon-like peptide-1 receptor agonists (GLP-1RA), particularly in regard to changes in FFM and skeletal muscle mass. The present article emphasizes the importance of fundamental principles when interpreting body composition changes experienced during weight loss, with a particular focus on GLP-1RA drug trials. The potential for obligatory loss of FFM due to reductions in adipose tissue mass and distribution of FFM loss from distinct body tissues are also discussed. Finally, selected countermeasures to combat loss of FFM and skeletal muscle, namely resistance exercise training and increased protein intake, are presented. Collectively, these considerations may allow for enhanced clarity when conceptualizing, discussing, and seeking to influence body composition changes experienced during weight loss.

Sex differences in the relationship between body composition and cardiac structure and function.

AIMS: The purpose of this study was to characterize sex differences in the relationship between body composition and cardiac structure and function. In secondary analyses, we explored pathophysiologic mediators of these relationships. METHODS AND RESULTS: In a cross-sectional analysis of 25,063 UK Biobank participants (54% female, median age 55 years), the sex-specific associations of visceral adipose tissue volume (VAT), appendicular lean mass (ALM), and muscle fat infiltration (MFI) with cardiac magnetic resonance (CMR) measures of cardiac structure and function were assessed using linear regression models. Using causal mediation analysis, 10 biomarkers were explored as mediators of the relationship between adipose depots and cardiac parameters. VAT was associated with increased left ventricular mass (LVM; ßwomen = 0.54, ßmen = 0.00, pint = 0.01) and wall thickness (ßwomen = 0.12, ßmen = 0.08, pint<0.001) in women only. A similar sex-specific pattern was observed for MFI effects on LVM (ßwomen = 0.44, ßmen = 0.03, pint<0.001). ALM was associated with increased LVM and LV volumes in both women and men. In mediation analyses, insulin resistance as measured by triglycerides/high density lipoprotein ratio was a potential partial mediator of VAT effects on chamber dimensions. CONCLUSIONS: In the largest and most rigorous analyses of body composition and cardiac parameters to date, we demonstrated that VAT is associated with increased LVM and wall thickness in women but not in men. MFI association with cardiac parameters was similar to VAT, significant in women but not in men.

Retrospective analysis of dual-energy x-ray absorptiometry data demonstrates body composition changes with age in dogs and cats.

OBJECTIVE: Use 18 years of dual-energy x-ray absorptiometry (DEXA) scan data to characterize how body composition changes with age in dogs and cats. METHODS: This was a retrospective observational study using data obtained from DEXA scans performed between 2006 and 2023. A total of 6,973 observations from 1,273 colony-housed dogs ≤ 1 to 16.1 years old and 6,593 observations from 1,096 colony-housed cats ≤ 1 to 16.9 years old were obtained. Animal ages were rounded to the nearest 1/10-year intervals. Means for each interval were calculated and quadratic, cubic, and quartic polynomial models were fit to assess trends over age. RESULTS: Age had an effect on all DEXA measurements. In dogs, lean mass increased early in life before slowing to a peak at age 6.3 and then declined gradually. Fat mass also increased until slowing to a peak at age 9.3 and then decreased. In cats, lean mass increased before slowing to a peak at age 4.5, decreased gradually until age 12.5, and then sharply declined. Fat mass increased until slowing to a peak at age 7.5 and then decreased gradually. CONCLUSIONS: This retrospective study provides a baseline for how body composition changes with age. Results suggest that lean mass loss may begin earlier than previously reported in dogs and cats. CLINICAL RELEVANCE: Sarcopenia and obesity are common conditions in aging pets. Results can be used to improve body composition assessment of patients and investigate the efficacy of nutritional interventions.

The quest for optimal ketamine dosing formula in treatment-resistant major depressive disorder.

BACKGROUND: Emerging evidence indicates that intravenous ketamine is effective in managing treatment-resistant unipolar and bipolar depression. Clinical studies highlight its favorable efficacy, safety, and tolerability profile within a dosage range of 0.5-1.0 mg/kg based on actual body weight. However, data on alternative dosage calculation methods, particularly in relation to body mass index (BMI) and therapeutic outcomes, remain limited. METHODS: This retrospective analysis of an open-label study aims to evaluate dose calculation strategies and their impact on treatment response among inpatients with treatment-resistant major depressive disorder (MDD) (n = 28). The study employed the Boer and Devine formulas to determine lean body mass (LBM) and ideal body weight (IBW), and the Mosteller formula to estimate body surface area (BSA). The calculated doses were then compared with the actual doses administered or converted to a dosage per square meter for both responders and non-responders. RESULTS: Regardless of treatment response, defined as a reduction of 50% in the Montgomery-Åsberg Depression Rating Scale, the use of alternative ketamine dosing formulas resulted in underdosing compared to the standardized dose of 0.5 mg/kg. Only two participants received higher doses (102.7% and 113.0%) when the Devine formula was applied. CONCLUSIONS: This study suggests that ketamine dosing formulas, alternative to the standardized 0.5 mg/kg based on body weight, may lead to underdosing and potentially impact outcome interpretation. To enhance dosing accuracy, future studies should consider incorporating body impedance analysis and waist-to-hip ratio measurements, as this study did not account for body composition.

Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults With Overweight and Insulin Resistance: Protocol for an Open-Labeled Randomized Controlled Trial.

BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. OBJECTIVE: This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. METHODS: This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m2) and prediabetes or well-controlled T2DM (hemoglobin A1c 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and ß galactosidase staining. RESULTS: The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. CONCLUSIONS: Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/62667.

Sex and obesity influence the relationship between perfluoroalkyl substances and lean body mass: NHANES 2011-2018.

Objective: Polyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass. Methods: We performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI. Results: Regression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI ( ß  = -0.193, 95 % confidence interval (CI): -0.325 to -0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant ( ß  = -0.294, 95 % CI: -0.495 to -0.094), and a similar trend was found in obese individuals ( ß  = -0.512, 95 % CI: -0.762 to -0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses. Conclusions: Our study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors.

Assessing skeletal muscle mass and lean body mass: an analysis of the agreement among dual X-ray absorptiometry, anthropometry, and bioelectrical impedance.

Introduction: Methods of body composition estimation such as dual-energy X-ray absorptiometry (DXA), anthropometry, and bioimpedance (BIA) are used for the estimation of skeletal muscle mass (SMM) and lean body mass (LBM). No previous studies have examined whether these methods generate comparable results, or whether they are valid by using DXA as the reference. The aims of the present investigation were: (a) to assess the differences between DXA, anthropometry, and BIA in the estimation of SMM and LBM, taking into consideration the impact of sex and hydration status; and (b) to examine the agreement of anthropometry and BIA as compared to DXA for the estimation of SMM and LBM. Methods: A descriptive cross-sectional design was followed with 262 healthy young adults (159 males and 103 females). LBM and SMM were assessed by anthropometry with the formulas from Lee et al. and Kulkarni et al. for LBM; and Kerr (opt a), Kerr (opt b), Lee et al., Poortmans, Matiegka, Martin et al., Drinkwater and Ross, and Heymsfield et al. for SMM; by BIA with the formula reported by the TANITA MC-780-MA software for LBM and SMM; and DXA with the formula reported by the Hologic Horizon software for LBM, and the conversion by Kim et al. for SMM. Results: Significant differences were found for both SMM and LBM in kg, and percentages between most methods and formulas for the overall sample (p < 0.001-0.003) and divided by sex (p < 0.001-0.035). Hydration status did not have a significant effect on the differences between methods and formulas (p = 0.058-0.870). Lin's coefficient revealed limited agreement among the majority of formulas and methods (CCC = 0.007-0.880). The Bland-Altman analysis showed significant differences in most methods and formulas, both in the overall sample and divided by sex, when using SMM and LBM with DXA as the reference (p < 0.001-0.030). Conclusion: There is a lack of agreement between methods and formulas for assessing SMM and LBM. Sex was found to be a significant factor in this analysis. Furthermore, significant differences were observed between most formulas and methods as compared to DXA, except for the equations to estimate SMM with anthropometry by Poortmans.

Effects of Different Exercises Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy. METHODS: We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: "Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis" (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves. RESULTS: The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (-3.64, 9.52); 2.37 (-0.40, 5.15); 1.80 (-1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (-0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (-0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (-1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are -1.60 (-6.98, 3.78); -2.76 (-7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are -0.52 (-2.58, 1.55); -1.83 (-4.71, 1.04); -2.46 (-5.69,0.76).). CONCLUSION: Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal.

Low Serum Total Carotenoids and ß-Cryptoxanthin Are Associated with Low Lean Body Mass in Older Community-Dwellers in the National Institute for Longevity Sciences-Longitudinal Study of Aging: A 4-Y Longitudinal Study.

BACKGROUND: Although diets rich in carotenoids are associated with muscle health and a reduced risk of disability, the relationship between carotenoids and low lean body mass has not been fully elucidated. OBJECTIVES: This study aimed to clarify the relationship between serum carotenoid concentrations and low lean body mass over 4 y in older Japanese community-dwellers. METHODS: A total of 750 adults aged ≥60 y participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging. Individuals with a low lean body mass and muscle strength or gait speed at baseline were excluded. Baseline serum α-carotene, ß-carotene, ß-cryptoxanthin, zeaxanthin, lutein, and lycopene were measured. Low lean body mass was defined as appendicular lean mass relative to the measured height (ALM/ht2) of <7.0 kg/m2 in males and <5.4 kg/m2 in females, according to the criteria of the Asian Working Group for Sarcopenia 2019. A generalized estimating equation was used to estimate the odds ratio and 95% confidence interval for low lean body mass according to tertiles of total and individual carotenoids at baseline, adjusted for sex, age, season, follow-up months, education years, economic status, current smoking status, a history of ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes mellitus, and metabolic equivalents. RESULTS: Low serum total carotenoids were associated with low ALM/ht2, and the odds ratios of low ALM/ht2 in the third tertile of total carotenoids were significantly lower than those in the first tertile after adjusting for covariates. The odds ratios of low ALM/ht2 in the third tertile of ß-cryptoxanthin were significantly associated with those in the first tertile after adjusting for covariates (P = 0.03); however, no trend was observed for this relationship. CONCLUSIONS: These findings indicate that low serum total carotenoids and serum ß-cryptoxanthin are associated with low lean body mass in older Japanese community-dwellers.

Resting energy expenditure in patients with liver cirrhosis: Indirect calorimetry vs. predictive equations.

BACKGROUND AND OBJECTIVES: The objective of our study was to explore the accuracy of previously published prediction equations in predicting resting energy expenditure (REE) in patients with liver cirrhosis (LC). We also aimed to develop a novel equation to estimate REE for Chinese patients with LC. METHODS AND STUDY DESIGN: In 90 patients with LC, the agreement between REE measured by Indirect calorimetry (IC) and predictive equations was quantified using paired T-test and visualized using a Bland-Altman Plot. Pearson correlation coefficient (R) was used to measure a linear correlation between REE measured by IC and different predictive equations. Stepwise multiple regression analysis was used to create a new REE equation. RESULTS: The estimated REEs of previous equations were underestimated against REE measured by IC (1610 ± 334 kcal). Lean body mass (LBM) was positively correlated with REE measured by IC (r = 0.723, p < 0.01). The newly derived estimation equation for REE (kcal) was 1274.3 - 209.0 * sex - 5.73 * age + 3.69 * waist circumference + 22.89 * LBM. The newly derived estimation equation was found to have a Pearson-r value of 0.765 compared with REE measured by IC. CONCLUSIONS: REE in liver cirrhosis was underestimated by using predictive equations. The new predictive equation developed by using age, sex, waist circumference, and LBM may help estimate REE in Chinese patients with LC accurately and easily.

Low muscle mass index is associated with type 2 diabetes risk in a Latin-American population: a cross-sectional study.

Objective: Diabetes mellitus is a growing disease with severe complications. Various scores predict the risk of developing this pathology. The amount of muscle mass is associated with insulin resistance, yet there is no established evidence linking muscle mass with diabetes risk. This work aims to study that relationship. Research methods and procedures: This cross-sectional study included 1,388 employees. The FINDRISC score was used to assess type 2 diabetes risk, and bioimpedance was used for body composition analysis. Appendicular skeletal muscle mass adjusted by body mass index (ASM/BMI) was analyzed. Sociodemographic, clinical and anthropometric measures were evaluated, logistic regression models with sex stratification were conducted and ROC curves were calculated to determine the ability of ASM/BMI index to predict T2D risk. Results: It was observed that patients with higher ASM/BMI had a lower FINDRISC score in both men and women (p < 0.001). A logistic regression model showed and association between ASM/BMI and diabetes risk in women [OR: 0.000 (0.000-0.900), p = 0.048], but not in men [OR: 0.267 (0.038-1.878), p = 0.185]. However, when the body mass index variable was excluded from the model, an association was found between muscle mass adjusted to BMI and diabetes risk in both men [OR: 0.000 (0.000-0.016), p < 0.001], and women [OR:0.001 (0.000-0.034), p < 0.001]. Other risk factors were having a low level of physical activity, waist circumference, age and sedentary lifestyle. A ROC curve was built and the optimal ASM/BMI cut-of value for predicting T2D risk was 0.82 with a sensitivity of 53.71% and specificity of 69.3% [AUC of 0.665 (0.64-0.69; p < 0.0001)]. Conclusion: When quantifying the risk of type 2 diabetes in both women and men, assessing muscle mass can help detect adult individuals with a high risk of developing type 2 diabetes.

Fluorine-18 FDG PET/CT and New NIMS Grading System for Chemotherapy Response in Breast Cancer.

Background: Positron emission tomography with computed tomography (PET-CT) using fluorine 18-fluorodeoxyglucose (F-18 FDG) is increasingly used to stage patients with locally advanced breast cancer and for assessing treatment response after neoadjuvant chemotherapy (NACT). Aims and Objectives: The aim of the study was to assess the correlation between PET-CT parameters and pathologic response of breast primary after NACT in breast cancer patients and to devise a grading system called NIMS grading system for response assessment using PET quantitative parameters. Materials and Methods: 55 patients who underwent F-18 FDG PET-CT before starting the therapy and again after completion of therapy were identified and included in the study. The clinical data and the histopathologic findings were recorded. All the patients received chemotherapy followed by surgery with axillary lymph node dissection. The PET-CT results were interpreted both qualitatively by visual analysis and quantitatively by estimating maximum Standardized uptake values(SUVmax) and other parameters - SUVmean, SUL, SUVBSA, Metabolic tumor volume (MTV) and Total lesion glycolysis (TLG). Results: The sensitivity and specificity of F-18 FDG PET-CT to detect the residual disease after neoadjuvant chemotherapy was 75.6% & 92.8% respectively. Differences between complete response and residual disease were significant for ΔSUVmax(p=0.005), ΔSUVmean(p=0.006), ΔSUL (0.005) and ΔSUVBSA(0.004), while ΔMTV and ΔTLG were not significantly different between the two groups. The new NIMS grading system included scoring of ΔSUVmax, ΔSUVBSA, ΔTLG and ΔMTV on scale of 1 to 4 and correlated well with PERCIST criteria. Conclusion: F-18 FDG PET-CT had a good accuracy in the detection of residual disease after completion of NACT. Pre chemotherapy PET-CT is not adequate to predict the response of primary tumour to chemotherapy. However, changes in the values of various PET-CT parameters are a sensitive tool to assess the response to chemotherapy. The new grading system is easy to use and showed good correlation to PERCIST.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy decreases lean body mass and appendicular skeletal muscle mass index even until one year after the final treatment in patients with B-cell non-Hodgkin lymphoma.

Sarcopenia is an independent prognostic factor for several solid cancers, including B-cell non-Hodgkin lymphoma (B-NHL). However, previous reports have measured the parameters of loss of skeletal muscle as sarcopenia only once before chemotherapy and have predicted poor outcomes. In this study, changes in body composition were measured in patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy for B-NHL using the InBody 720 analyzer throughout the therapy. Twenty-seven patients who achieved complete remission and survived for one year after the last cycle were included in the study. Body composition was evaluated immediately before initiation and fourth cycle, and one month and one year after the last cycle. Throughout the follow-up period, the lean body mass index (LBMI) and appendicular skeletal muscle mass index (ASMI) showed significant transient decreases even one year following the last cycle (p < 0.001, p = 0.002, respectively). Body fat index (BFI) and body fat percentage (BF%) decreased until one month after the last cycle; however, they reached levels higher than the baseline levels, +22.1% and +15.9%, respectively, at 1 year from the last cycle. The loss of skeletal muscle mass did not recover even one year after the last cycle. Interventions in nutritional management are needed to prevent sarcopenia in patients treated with R-CHOP therapy.

Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model.

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

Association between institutionalization by 4 months post-discharge walking capacity and lean body mass in elderly hip fracture patients: Evidence from a Swedish Registry Based Study.

Background and purpose: Losing independence is a main concern for hip fracture patients, and particularly not being able to return home. Given the large impact on quality of life by loss of independence and the high risk for institutionalization after hip fracture, it is of importance to identify modifiable risk factors for such negative outcomes. This study aimed to investigate the association between two such factors, that is, lean body mass and 4 months post-discharge walking capacity, and the risk of institutionalization in previously independent living older people who suffer a hip fracture. Patients and methods: A retrospective cohort study was conducted using Swedish national-based population registers. Patients ⩾60 years with a hip fracture during 2008-2017 were included from the Swedish National Registry for Hip Fractures. Risk of institutionalization over the 1-year period following a hip fracture was analyzed using logistic regression analyses adjusted for potential predictors and characteristics. Results: In total, 11,265 patients were included. Over the first year, 8% (95% CI: 8-9) of the patients with a hip fracture had lost independence, increasing to 15% (95% CI: 14-16) after 5 years. Poor recovery of post-discharge walking ability was associated with a higher odds ratio of losing independence compared with good recovery (OR 12.0; 95% CI: 7.8-18.4; p < 0.001). Having higher estimated lean body mass than 45 kg at index was associated with lower odds of losing independence. Conclusion: Maintaining lean body mass and mobility after a hip fracture is likely important from an individual as well as public health perspective.

Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus.

Background: Glucagon-like peptide-1 receptor-agonists (GLP-1ra), such as semaglutide, have emerged as promising treatments, demonstrating sustained weight reduction and metabolic benefits. This study aims to assess the impact of oral and subcutaneous semaglutide on body composition and metabolic parameters in patients with T2DM and obesity. Methods: A 24-week quasi-experimental retrospective study including adults with T2DM and obesity (BMI ≥ 30 kg/m²) who were treated with either daily-oral or weekly-subcutaneous semaglutide. Body composition was measured using bioelectrical impedance analysis, evaluating fat mass, fat-free mass, total body water, skeletal muscle mass, and whole-body phase angle. Analytical parameters included lipid profile and glycaemic control. Statistical analyses were performed using SPSS v.26. Results: Participants (n=88) experienced significant weight loss after treatment with semaglutide (9.5% in subcutaneous, 9.4% in oral, P<0.001). Weight reduction primarily resulted from fat mass reduction without substantial lean mass compromise. Visceral fat area decreased, whiles phase-angle remained stable. Improvements in lipid profiles and glycaemic control were observed, with a decrease in both HbA1c and insulin requirements. Multivariate analysis demonstrated comparable impacts of oral and subcutaneous semaglutide on body composition. Conclusion: Semaglutide, administered orally or subcutaneously, demonstrated positive effects on body composition, metabolic and glycaemic control in patients with T2DM and obesity. This real-world study highlights the potential of bioelectrical impedance analysis in assessing antidiabetic drugs' impact on body composition, providing valuable insights for future research and clinical applications.

Vancomycin population pharmacokinetics and dosing proposal for the initial treatment in obese adult patients.

Aim: The aim of this study was to develop a vancomycin population pharmacokinetic model in adult obese patients and propose covariate-based dosing individualization in order to maximize the achievement of the newly recommended PK/PD target, according to a revised consensus guideline from 2020. Methods: Therapeutic drug monitoring data from initial vancomycin therapy (first 3 days of treatment) in adult obese (BMI ≥ 30 kg/m2) patients from 2013 to 2022 were analyzed using a non-linear mixed-effects modeling method, and Monte Carlo simulations were then used to find the optimal dosage maximizing the PK/PD target attainment. Results: A total of 147 vancomycin serum levels obtained from 138 patients were included in the analysis. Based on the covariate model diagnosis among all tested variables, no reliable predictor of vancomycin volume of distribution (Vd) was identified, while clearance (CL) was positively correlated with eGFR and lean body mass. Creatinine-based eGFR predicted vancomycin CL better than cystatin C-based eGFR. The median (interquartile range) value from conditional modes of individual estimates of Vd, CL, and elimination half-life in our population was 74.0 (70.5-75.4) L, 6.65 (4.95-8.42) L/h, and 7.7 (6.0-10.0) h, respectively. Conclusion: We proposed dosing individualization based on the covariate found in order to maximize the achievement of the newly recommended PK/PD target of the AUC/MIC ratio of 400-600. Clinical pharmacy/pharmacology interventions may lead to an improvement in vancomycin dosing with a reflection in PK/PD target attainment.

Effectiveness of Nutritional Guidance Focusing on Leucine Intake During Cardiac Rehabilitation Maintenance.

Objective: Due to the lack of information on the effects of nutritional guidance focused on leucine intake in patients undergoing maintenance cardiac rehabilitation, this study investigated on plasma leucine concentrations, lean body mass, and muscle strength. Methods: Nutritional guidance, focused on leucine (intervention group) or general nutritional guidance (control group), was provided for six months to patients participating in cardiac rehabilitation. Body composition, grip strength, hematological test results, and diet of both groups were compared before and after the intervention. Results: Seven patients in the intervention group (53.2 ±â€…18.2 years) and 7 patients in the control group (58.6 ±â€…15.3 years) were included. Dietary survey results showed that the six-month intervention significantly (p < 0.05) increased protein intake and estimated leucine intake only in the intervention group. There was no significant difference in the rate of change in plasma leucine concentration between the two groups. The rate of change in lean body mass was significantly higher in the intervention group compared to the control group (p = 0.035). The rate of change in plasma leucine concentration and that in lean body mass was positively correlated only in the intervention group (r = 0.777, p = 0.040), and the rate of change in plasma leucine concentration was also positively correlated with the rate of change in grip strength (ρ = 0.857, p = 0.014). Conclusions: In the patients undergoing maintenance cardiac rehabilitation, increased plasma leucine concentration by nutritional guidance focused on leucine increased lean body mass without any increasing the training load.

Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters.

Introduction: The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers. Methods: Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers. We evaluated fecal microbiota composition (assessed via bacterial 16S rRNA gene sequencing), fecal IgA levels, surrogate markers of gut permeability, serum cytokines, appetite mediators, nutritional status, physical activity, and quality of life. Results: HD patients exhibited significant alterations in fecal microbiota composition compared to healthy volunteers, with observed shifts in taxa known to be associated with dietary patterns or producing metabolites acting on human host. In comparison to healthy volunteers, individuals with HD patients exhibited elevated levels of inflammatory markers (CRP, IL-6 and TNF-α), glucagon-like peptide-2, and potential anorexigenic markers (including leptin and peptide YY). NHD patients had increased levels of CRP and peptide YY. Overall fecal microbiota composition was associated with height, soft lean mass, resting energy expenditure, handgrip strength, bone mineral content and plasma albumin and TNF-α. Discussion: Compared to healthy volunteers, HD patients have an altered fecal microbiota composition, a higher systemic inflammation, and a modification in plasma levels of appetite mediators. While some differences align with previous findings, heterogeneity exists likely due to various factors including lifestyle and comorbidities. Despite limitations such as sample size, our study underscores the multifaceted interplay between gut microbiota, physiological markers, and kidney function, warranting further investigation in larger cohorts.