Prediction of hematologic toxicity in luminal type breast cancer patients receiving neoadjuvant chemotherapy using CT L1 level skeletal muscle index.

This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of < 32.91 cm2/m2, initial tumor size ≥ 3.335 cm, and a glucose-to-neutrophil ratio (GLR) ≥ 2.88 were identified as independent risk factors for severe hematologic toxicity during neoadjuvant chemotherapy in luminal-type breast cancer patients. The sample size in this study is small, and the predictive capacity of GLR in hematologic toxicity requires further research for comprehensive validation. CT-L1 analysis represents a viable alternative to CT-L3 analysis for body composition assessment. Patients with a low skeletal muscle index were more prone to experiencing severe hematologic toxicity during neoadjuvant chemotherapy.

Biceps femoris long head muscle and aponeurosis geometry in males with and without a history of hamstring strain injury.

OBJECTIVES: Hamstring strain injuries (HSIs) commonly affect the proximal biceps femoris long head (BFlh) musculotendinous junction. Biomechanical modeling suggests narrow proximal BFlh aponeuroses and large muscle-to-aponeurosis width ratios increase localized tissue strains and presumably risk of HSI. This study aimed to determine if BFlh muscle and proximal aponeurosis geometry differed between limbs with and without a history of HSI. METHODS: Twenty-six recreationally active males with (n = 13) and without (n = 13) a history of unilateral HSI in the last 24 months underwent magnetic resonance imaging of both thighs. BFlh muscle and proximal aponeurosis cross-sectional areas, length, volume, and interface area between muscle and aponeurosis were extracted. Previously injured limbs were compared to uninjured contralateral and control limbs for discrete variables and ratios, and along the relative length of tissues using statistical parametric mapping. RESULTS: Previously injured limbs displayed significantly smaller muscle-to-aponeurosis volume ratios (p = 0.029, Wilcoxon effect size (ES) = 0.43) and larger proximal BFlh aponeurosis volumes (p = 0.019, ES = 0.46) than control limbs with no history of HSI. No significant differences were found between previously injured and uninjured contralateral limbs for any outcome measure (p = 0.216-1.000, ES = 0.01-0.36). CONCLUSIONS: Aponeurosis geometry differed between limbs with and without a history of HSI. The significantly larger BFlh proximal aponeuroses and smaller muscle-to-aponeurosis volume ratios in previously injured limbs could alter the strain experienced in muscle adjacent to the musculotendinous junction during active lengthening. Future research is required to determine if geometric differences influence the risk of re-injury and whether they can be altered via targeted training.

Two synergistic types of muscles were detected during forearm rotation exercise by T2 cumulative frequency curves using 0.2 T magnetic resonance imaging.

The purpose of this study was the detection and characterization of synergistic muscle activity. Using T2-map MRI, T2 values for 10 forearm muscles in 11 healthy adult volunteers were obtained in the resting state and after isotonic forearm supination and pronation exercises with the elbow extended. T2 was normalized by Z = (T2e-T2r)/SDr, where T2e was T2 after exercise, while T2r and SDr were the reference values of 34 ms and 3 ms, respectively. Using the cumulative frequency curves of Z values (CFZ), we detected 2 and 3 synergistic muscles for supination and pronation, respectively, and divided these into 2 types, one activated by exercise strength dependently, and the other, independent of exercise strength, activated by only a smaller fraction of the participants. We also detected co-contraction for the supination. Thus, CFZ is a useful visualization tool to detect and characterize not only synergistic muscle, but also co-contraction muscle.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Myofascial trigger point (MTrP) size and elasticity properties can be used to differentiate characteristics of MTrPs in lower back skeletal muscle.

Myofascial trigger points (MTrPs) are localized contraction knots that develop after muscle overuse or an acute trauma. Significant work has been done to understand, diagnose, and treat MTrPs in order to improve patients suffering from their effects. However, effective non-invasive diagnostic tools are still a missing gap in both understanding and treating MTrPs. Effective treatments for patients suffering from MTrP mediated pain require a means to measure MTrP properties quantitatively and diagnostically both prior to and during intervention. Further, quantitative measurements of MTrPs are often limited by the availability of equipment and training. Here we develop ultrasound (US) based diagnostic metrics that can be used to distinguish the biophysical properties of MTrPs, and show how those metrics can be used by clinicians during patient diagnosis and treatment. We highlight the advantages and limitations of previous US-based approaches that utilize elasticity theory. To overcome these previous limitations, we use a hierarchical approach to distinguish MTrP properties by patients' reported pain and clinician measured palpation. We show how US-based measurements can characterize MTrPs with this approach. We demonstrate that MTrPs tend to be smaller, stiffer, and deeper in the muscle tissue for patients with pain compared to patients without pain. We provide evidence that more than one MTrP within a single US-image field increases the stiffness of neighboring MTrPs. Finally, we highlight a combination of metrics (depth, thickness, and stiffness) that can be used by clinicians to evaluate individual MTrPs in combination with standard clinical assessments.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

OBJECTIVES: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity. METHODS: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m2. The hazard ratio (HR) for death was calculated using Cox regression analysis. RESULTS: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013). CONCLUSION: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy.

Quantifying the severity of sarcopenia in patients with cancer of the head and neck.

BACKGROUND & AIMS: Existing skeletal muscle index (SMI) thresholds for sarcopenia are inconsistent, and do not reflect severity of depletion. In this study we aimed to define criterion values for moderate and severe skeletal muscle depletion based on the risk of mortality in a population of patients with head and neck cancer (HNC). Additionally, we aimed to identify clinical and demographic predictors of skeletal muscle depletion, evaluate the survival impact of skeletal muscle depletion in patients with minimal nutritional risk or good performance status, and finally, benchmarking SMI values of patients with HNC against healthy young adults. METHODS: Population cohort of 1231 consecutive patients and external validation cohorts with HNC had lumbar SMI measured by cross-sectional imaging. Optimal stratification determined sex-specific thresholds for 2-levels of SMI depletion (Class I and II) based on overall survival (OS). Adjusted multivariable regression analyses (tumor site, stage, performance status, age, sex, dietary intake, weight loss) determined relationships between 2-levels of SMI depletion and OS. RESULTS: Mean SMI (cm2/m2) was 51.7 ± 9.9 (males) and 39.8 ± 7.1 (females). The overall and sex-specific population demonstrated an increased risk of mortality associated with decreasing SMI. Sex-specific SMI (cm2/m2) depletion thresholds for 2-levels of muscle depletion determined by optimal stratification for males and females, respectively (male: 45.2-37.5, and <37.5; female: 40.9-34.2, and <34.2). In the overall population, Normal SMI, Class I and II SMI depletion occurred in 65.0%, 24.0%, and 11.0%, respectively. Median OS was: Normal SMI (114 months, 95% CI, 97.1-130.8); Class I SMI Depletion (42 months, 95% CI, 28.5-55.4), and Class II SMI Depletion (15 months, 95% CI, 9.8-20.1). Adjusted multivariable analysis compared with Normal SMI (reference), Class I SMI Depletion (HR, 1.49; 95% CI, 1.18-1.88; P < .001), Class II SMI Depletion (HR, 1.91; 95% CI, 1.42-2.58; P < .001). CONCLUSIONS: Moderate and severe SMI depletion demonstrate discrimination in OS in patients with HNC. Moderate and severe SMI depletion is prevalent in patients with minimal nutrition risk and good performance status. Benchmarking SMI values against healthy young adults exemplifies the magnitude of SMI depletion in patients with HNC and may be a useful method in standardizing SMI assessment.

Reliability of muscle stiffness measures in popliteus, medial and lateral gastrocnemius muscles by ultrasound shear wave elastography in participants with knee osteoarthritis accompanied by myofascial trigger points.

BACKGROUND: The objective of this investigation is to evaluate the consistency of intra-rater and inter-rater assessments utilizing ultrasound elastography to examine the muscle stiffness of the popliteus and gastrocnemius (medial and lateral heads) in patients with knee osteoarthritis accompanied by myofascial trigger points. METHODS: Thirty individuals with knee osteoarthritis accompanied by myofascial trigger points were assessed. Two examiners independently measured the muscle stiffness levels of the popliteus and gastrocnemius (medial and lateral heads) three times using ultrasound elastography in the first session. The second session was conducted one week later. RESULTS: In the initial test session, the mean shear modulus values for the popliteus and gastrocnemius (medial and lateral heads) muscles were measured as follows for tester 1 (12.75, 13.72, 14.13 kPa) and tester 2 (11.66, 12.81, 13.17 kPa). During the retest session, the previously measured variables by tester 1 and tester 2 yielded the following values: (12.61, 13.43, 14.26 kPa) and (11.62, 12.87, 13.30 kPa) respectively." Good to excellent intra-rater reliability (ICC = 0.912-0.986) and inter-rater reliability (ICC = 0.766-0.956) were reported for the shear moduli of the popliteus, medial and lateral gastrocnemius muscles. CONCLUSIONS: The assessment of muscle stiffness in the popliteus and gastrocnemius (medial and lateral heads) using ultrasound elastography is a reliable method in patients with knee osteoarthritis accompanied by myofascial trigger points.

CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

BACKGROUND: Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. METHODS: Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). RESULTS: 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. CONCLUSIONS: Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

Skeletal Muscle Compliance and Echogenicity in Resistance-Trained and Nontrained Women.

ABSTRACT: Mongold, SJ, Ricci, AW, Hahn, ME, and Callahan, DM. Skeletal muscle compliance and echogenicity in resistance-trained and nontrained women. J Strength Cond Res 38(4): 671-680, 2024-Noninvasive assessment of muscle mechanical properties in clinical and performance settings tends to rely on manual palpation and emphasizes examination of musculotendinous stiffness. However, measurement standards are highly subjective. The purpose of the study was to compare musculotendinous stiffness in adult women with varying resistance training history while exploring the use of multiple tissue compliance measures. We identified relationships between tissue stiffness and morphology, and tested the hypothesis that combining objective measures of morphology and stiffness would better predict indices of contractile performance. Resistance-trained (RT) women (n = 11) and nontrained (NT) women (n = 10) participated in the study. Muscle echogenicity and morphology were measured using B-mode ultrasonography (US). Vastus lateralis (VL) and patellar tendon (PT) stiffness were measured using digital palpation and US across submaximal isometric contractions. Muscle function was evaluated during maximal voluntary isometric contraction (MVIC) of the knee extensors (KEs). Resistance trained had significantly greater PT stiffness and reduced echogenicity (p < 0.01). Resistance trained also had greater strength per body mass (p < 0.05). Muscle echogenicity was strongly associated with strength and rate of torque development (RTD). Patellar tendon passive stiffness was associated with RTD normalized to MVIC (RTDrel; r = 0.44, p < 0.05). Patellar tendon stiffness was greater in RT young women. No predictive models of muscle function incorporated both stiffness and echogenicity. Because RTDrel is a clinically relevant measure of rehabilitation in athletes and can be predicted by digital palpation, this might represent a practical and objective measure in settings where RTD may not be easy to measure directly.

Ultrasound-based assessment of the expression of inflammatory markers in the rectus femoris muscle of rats.

Ultrasonographic characteristics of skeletal muscles are related to their health status and functional capacity, but they still provide limited information on muscle composition during the inflammatory process. It has been demonstrated that an alteration in muscle composition or structure can have disparate effects on different ranges of ultrasonogram pixel intensities. Therefore, monitoring specific clusters or bands of pixel intensity values could help detect echotextural changes in skeletal muscles associated with neurogenic inflammation. Here we compare two methods of ultrasonographic image analysis, namely, the echointensity (EI) segmentation approach (EI banding method) and detection of selective pixel intensity ranges correlated with the expression of inflammatory regulators using an in-house developed computer algorithm (r-Algo). This study utilized an experimental model of neurogenic inflammation in segmentally linked myotomes (i.e., rectus femoris (RF) muscle) of rats subjected to lumbar facet injury. Our results show that there were no significant differences in RF echotextural variables for different EI bands (with 50- or 25-pixel intervals) between surgery and sham-operated rats, and no significant correlations among individual EI band pixel characteristics and protein expression of inflammatory regulators studied. However, mean numerical pixel values for the pixel intensity ranges identified with the proprietary r-Algo computer program correlated with protein expression of ERK1/2 and substance P (both 86-101-pixel ranges) and CaMKII (86-103-pixel range) in RF, and were greater (p < 0.05) in surgery rats compared with their sham-operated counterparts. Our findings indicate that computer-aided identification of specific pixel intensity ranges was critical for ultrasonographic detection of changes in the expression of inflammatory mediators in neurosegmentally-linked skeletal muscles of rats after facet injury.

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

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

Low Muscle Mass by Preprocedural Computed Tomography Is Associated With Worse Short-Term Outcomes in Transcatheter Aortic Valve Replacement Recipients.

Low muscle mass (LMM) is associated with worse outcomes in various clinical situations. Traditional frailty markers have been used for preoperative risk stratification in patients who underwent transcatheter aortic valve replacement (TAVR). However, preoperative imaging provides an opportunity to directly quantify skeletal muscle mass to identify patients at higher risk of procedural complications. We reviewed all TAVR recipients from January to December 2018 and included subjects with preprocedural chest computed tomography. Multi-slice automated measurements of skeletal muscle mass were made from the ninth to twelfth thoracic vertebrae and normalized by height squared to obtain skeletal muscle index (cm2/m2). LMM was defined as the lowest gender-stratified skeletal muscle index tertile. Strength testing was collected during pre-TAVR evaluation. Primary outcome was a composite of perioperative complications, 1-year rehospitalization, or 1-year mortality. In our cohort, 238 patients met inclusion criteria, and 80 (33.6%) were identified to have LMM. Patients with LMM were older with lower body mass index, decreased grip strength, lower hemoglobin A1c, and higher N-terminal pro-brain natriuretic peptide. They had greater rates of the composite outcome and 2-year all-cause mortality, which remained significant on multivariable adjustment (hazard ratio 1.71, 95% confidence interval 1.05 to 2.78, p = 0.030 and hazard ratio 2.31, 95% confidence interval 1.02 to 5.24, p = 0.045, respectively) compared with patients without LMM; there was no significant difference in 5-year all-cause mortality. In conclusion, LMM was associated with an increase in the primary composite outcome and 2-year all-cause mortality in TAVR recipients. Using automatic muscle processing software on pre-TAVR computed tomography scans may serve as an additional preoperative risk stratification tool.

Ethnic differences in CT derived abdominal body composition measures: a comparative retrospect pilot study between European and Inuit study population.

Understanding ethnic variations in body composition is crucial for assessing health risks. Universal models may not suit all ethnicities, and there is limited data on the Inuit population. This study aimed to compare body composition between Inuit and European adults using computed tomography (CT) scans and to investigate the influence of demographics on these measurements. A retrospective analysis was conducted on 50 adults (29 Inuit and 21 European) who underwent standard trauma CT scans. Measurements focused on skeletal muscle index (SMI), various fat indices, and densities at the third lumbar vertebra level, analyzed using the Wilcoxon-Mann-Whitney test and multiple linear regression. Inuit women showed larger fat tissue indices and lower muscle and fat densities than European women. Differences in men were less pronouncehd, with only Intramuscular fat density being lower among Inuit men. Regression indicated that SMI was higher among men, and skeletal muscle density decreased with Inuit ethnicity and age, while visceral fat index was positively associated with age. This study suggests ethnic differences in body composition measures particularly among women, and indicates the need for Inuit-specific body composition models. It higlights the importance of further research into Inuit-specific body composition measurements for better health risk assessment.

Comparison of the accuracy of commercial two-point and multi-echo Dixon MRI for quantification of fat in liver, paravertebral muscles, and vertebral bone marrow.

PURPOSE: Excess fat accumulation contributes significantly to metabolic dysfunction and diseases. This study aims to systematically compare the accuracy of commercially available Dixon techniques for quantification of fat fraction in liver, skeletal musculature, and vertebral bone marrow (BM) of healthy individuals, investigating biases and sex-specific influences. METHOD: 100 healthy White individuals (50 women) underwent abdominal MRI using two-point and multi-echo Dixon sequences. Fat fraction (FF), proton density fat fraction (PDFF) and T2* values were calculated for liver, paravertebral muscles (PVM) and vertebral BM (Th8-L5). Agreement and systematic deviations were assessed using linear correlation and Bland-Altman plots. RESULTS: High correlations between FF and PDFF were observed in liver (r = 0.98 for women; r = 0.96 for men), PVM (r = 0.92 for women; r = 0.93 for men) and BM (r = 0.97 for women; r = 0.95 for men). Relative deviations between FF and PDFF in liver (18.92 % for women; 13.32 % for men) and PVM (1.96 % for women; 11.62 % for men) were not significant. Relative deviations in BM were significant (38.13 % for women; 27.62 % for men). Bias correction using linear models reduced discrepancies. T2* times were significantly shorter in BM (8.72 ms for women; 7.26 ms for men) compared to PVM (13.45 ms for women; 13.62 ms for men) and liver (29.47 ms for women; 26.35 ms for men). CONCLUSION: While no significant differences were observed for liver and PVM, systematic errors in BM FF estimation using two-point Dixon imaging were observed. These discrepancies - mainly resulting from organ-specific T2* times - have to be considered when applying two-point Dixon approaches for assessment of fat content. As suitable correction tools, linear models could provide added value in large-scale epidemiological cohort studies. Sex-specific differences in T2* should be considered.

Preoperative Body Composition Correlates with Postoperative Muscle Volume and Degeneration after Total Hip Arthroplasty.

Impaired muscle recovery after total hip arthroplasty (THA) may affect gait and activities of daily living. Bioelectrical impedance analysis (BIA) can assess body composition and muscle volume, and computed tomography (CT) can assess muscle volume and the fatty degeneration of muscle. This study aimed to explore the effectiveness of BIA, and the correlation between preoperative body composition and postoperative muscle volume and degeneration after THA using BIA and CT. Thirty-eight patients who underwent THA and had BIA and CT performed pre- and postoperatively were retrospectively assessed. The BIA-derived measurements of preoperative body composition (fat mass index, fat-free mass index, and phase angle) were correlated with the CT-derived measurements (pre- and postoperative muscle volume and gluteus maximus and quadriceps Hounsfield Units of the affected hip). The preoperative fat mass index negatively correlated with the postoperative muscle volume of the gluteus maximus (p = 0.02) and quadriceps (p < 0.001) and the Hounsfield Units of the gluteus maximus (p = 0.03) and quadriceps (p = 0.03). The preoperative fat-free mass index positively correlated with the postoperative muscle volume of the quadriceps (p = 0.02). The preoperative phase angle positively correlated with the postoperative muscle volume of the quadriceps (p = 0.001) and the Hounsfield Units of the gluteus maximus (p = 0.03) and quadriceps (p = 0.001). In patients who underwent THA, preoperative body composition correlated with postoperative muscle volume and the fatty degeneration of the affected lower limb. Preoperative body composition may help predict postoperative muscle volume and fatty degeneration and thus, postoperative recovery.

Quantification of Skeletal Muscle Perfusion in Peripheral Artery Disease Using 18F-Sodium Fluoride Positron Emission Tomography Imaging.

BACKGROUND: Perfusion deficits contribute to symptom severity, morbidity, and death in peripheral artery disease (PAD); however, no standard method for quantifying absolute measures of skeletal muscle perfusion exists. This study sought to preclinically test and clinically translate a positron emission tomography (PET) imaging approach using an atherosclerosis-targeted radionuclide, fluorine-18-sodium fluoride (18F-NaF), to quantify absolute perfusion in PAD. METHODS AND RESULTS: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic 18F-NaF PET/computed tomography imaging on the day of and 2 weeks after occlusion. Following 2-week imaging, calf muscles were harvested to quantify microvascular density. PET methodology was validated with microspheres in 4 additional pig studies and translated to patients with PAD (n=39) to quantify differences in calf perfusion across clinical symptoms/stages and perfusion responses in a case of revascularization. Associations between PET perfusion, ankle-brachial index, toe-brachial index, and toe pressure were assessed in relation to symptoms. 18F-NaF PET/computed tomography quantified significant deficits in calf perfusion in pigs following arterial occlusion and perfusion recovery 2 weeks after occlusion that coincided with increased muscle microvascular density. Additional studies confirmed that PET-derived perfusion measures agreed with microsphere-derived perfusion measures. Translation of imaging methods demonstrated significant decreases in calf perfusion with increasing severity of PAD and quantified perfusion responses to revascularization. Perfusion measures were also significantly associated with symptom severity, whereas traditional hemodynamic measures were not. CONCLUSIONS: 18F-NaF PET imaging quantifies perfusion deficits that correspond to clinical stages of PAD and represents a novel perfusion imaging strategy that could be partnered with atherosclerosis-targeted 18F-NaF PET imaging using a single radioisotope injection. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.

Relationship between low relative muscle mass and aortic regional morphological changes in adults underwent contrast CT scans for cancer diagnostics.

OBJECTIVES: Low muscle mass is related to cardiovascular risk factors. This study aimed to investigate whether relative low muscle mass is related to the diameter and tortuosity of the aorta. METHODS: We performed a cross-sectional study of 208 adults without known cardiovascular disease who underwent Computed Tomography (CT) enhanced scan between 2020 and 2021. Skeletal muscle index (SMI) was estimated. The morphology of the aorta was measured by diameter and tortuosity using CT. We assessed the relationship between SMI and diameter and tortuosity of the aorta using Spearman correlation analysis and univariate and multivariate-adjusted regression models. RESULTS: Of all -individuals, 124 (59.6%) were male. The average age was 60.13 ± 16.33 years old. SMI was inversely associated with the diameter and tortuosity of the aorta (p < 0.05). Specifically, in a multivariable-adjusted model adjusting for potential confounders, a one-unit increase in the SMI was associated with a -13.56mm(95% confidence intervals (CI): -18.16 to -8.96, p < 0.001), -7.93 mm (95% CI: -10.85 to -5.02, p < 0.001), -8.01 mm (95% CI: -11.30 to -4.73, p < 0.001), -5.16 mm (95% CI: -7.57 to -2.75, p < 0.001) and -2.73 mm (95% CI: -5.18 to -0.27, p = 0.031) increase in L1-L5 diameter respectively, a -0.89 (95% CI: -1.14 to -0.64, p < 0.001) increase in the aorta tortuosity, a -0.48 (95% CI: -0.59 to -0.36, p < 0.001) increase in the descending thoracic aorta tortuosity, and a -0.44 (95% CI: -0.52 to -0.35, p < 0.001) increase in the abdominal aorta tortuosity. CONCLUSIONS: Relative muscle mass was negatively associated with the diameter and tortuosity of the aorta, suggesting muscle mass maintenance may play a role in preventing aortic morphological changes.

Association of Sarcopenia, as Defined Based on the Skeletal Muscle Index, With Mortality and Morbidity After Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: To investigate whether "sarcopenia," defined based on the preoperative skeletal muscle index (SMI), can predict major postoperative morbidity and all-cause mortality. DESIGN: A retrospective observational cohort study. SETTING: At the authors' Department of Critical Care Medicine. PARTICIPANTS: A total of 986 adult Chinese patients underwent cardiac surgery (coronary artery bypass graft, valve surgery, combined surgery, or aortic surgery) between January 2019 and August 2022. MEASUREMENTS AND MAIN RESULTS: The skeletal muscle area at the third lumbar level (L3) was measured via preoperative computed tomography (up to 3 months from the date of imaging to the date of surgery) and normalized to patient height (skeletal muscle index). Sarcopenia was determined based on the skeletal muscle index being in the lowest sex-specific quartile. The primary outcome was all-cause mortality. The secondary outcome was major morbidity. A total of 968 patients were followed for a median of 2.00 years, ranging from 1.06 to 2.90 years. After the follow-up, 76 patients died during the follow-up period. Multivariate Cox proportional analysis showed a relationship between sarcopenia (adjusted hazard ratio 1.80, 95% CI 1.04-3.11; p = 0.034) and all-cause mortality. Kaplan-Meier curves revealed a significantly lower survival rate in the sarcopenia group than in the nonsarcopenia group. Overall, 199 (20.6%) patients had major morbidity. Multivariate analysis showed a significant relationship between sarcopenia (adjusted odds ratio = 2.21, 95% CI 1.52∼3.22, p < 0.001) and major morbidity. CONCLUSIONS: Sarcopenia, defined by the skeletal muscle index, is associated with all-cause mortality and major morbidity after cardiac surgery, thereby suggesting the need for perioperative sarcopenia risk assessment for patients undergoing cardiac surgery to guide the prevention and management of adverse outcomes.

Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.

OBJECTIVE: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series. METHODS: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant. RESULTS: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing. INTERPRETATION: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease.