The Association of Carbohydrate Antigen (CA) 19-9 Levels and Low Skeletal Muscle Mass in Healthy Adults.

Carbohydrate antigen 19-9 (CA 19-9) is a commonly used tumor marker for pancreatic cancer. However, CA 19-9 can be overexpressed in several benign inflammatory diseases. We investigated the relationship between high CA 19-9 level and low muscle mass (LMM) in healthy adults without cancer. Participants who underwent evaluation of muscle mass and CA 19-9 were included. Exclusion criteria were any malignancy, cardiovascular disease, tuberculosis, and chronic lung/liver disease. Participants were classified into "normal", "mild LMM", and "severe LMM" groups based on the skeletal muscle mass index. Multivariable logistic regression analyses were conducted to assess the association of high CA 19-9 with muscle mass status. A total of 263,061 adults were included. The mean age and SMI were 41.03 years and 7.13 kg/m2. After adjustments for various confounders, high CA 19-9 was independently associated with mild LMM (adjusted odds ratio, 1.677 [95% confidence interval, 1.533-1.834]) and severe LMM (2.651 [2.126-3.306]) compared to the normal group. Furthermore, the association between high CA 19-9 and severe LMM was stronger in men than in women. Elevated CA 19-9 levels were independently associated with a higher prevalence of LMM in healthy adults without cancer. Therefore, increased CA 19-9 could be utilized as a novel biomarker for sarcopenia.

Association of Pulmonary Function with Osteosarcopenic Obesity in Older Adults Aged over 50 Years.

Osteosarcopenic obesity (OSO) is a newly described coexistence of osteopenia/osteoporosis, sarcopenia, and obesity. We examined the association between pulmonary function, OSO, and its composition in adults aged ≥ 50 years. A total of 26,343 participants (8640 men; 17,703 women) were classified into four groups based on the number of abnormal body compositions (osteopenia/osteoporosis, sarcopenia, and obesity): 0 (control), 1+, 2+, and 3+ (OSO) abnormal body compositions. The values of forced volume vital capacity (FVC)%, forced expiratory volume in 1 s (FEV1%), and FEV1/FVC% were significantly decreased by increasing the number of adverse body compositions (p < 0.0001). Although the prevalence of restrictive spirometry pattern (RSP) was positively associated with a higher number of abnormal body composition parameters (p < 0.001), obstructive spirometry pattern (OSP) had no association with adverse body composition. In multivariate analyses, the adjusted odds ratios (ORs) for RSP compared to the control group were 1.36 in 1+, 1.47 in 2+, and 1.64 in 3+ abnormal body compositions (p for trend < 0.001). Multiple abnormal body composition, especially osteosarcopenic obesity, was independently associated with poor lung function showing RSP in older adults over 50 years. The coexistence of these abnormal body compositions may be a predisposing factor for pulmonary function deterioration.

Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study.

BACKGRUOUND: Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted. METHODS: We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (-2 standard deviation [SD] < SMI ≤-1 [SD]), and severely LMM groups (SD ≤-2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors. RESULTS: This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89). CONCLUSION: Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Sex-specific associations between gut microbiota and skeletal muscle mass in a population-based study.

BACKGROUND: A gut-muscle axis through which the microbiome influences skeletal muscle has been hypothesized. However, sex-specific association between the characteristics of gut microbiota and skeletal muscle mass has not yet been reported. Herein, we performed sex-specific analyses of faecal microbiota composition for the skeletal muscle mass in a population-based cohort. METHODS: We collected faecal samples of 1052 middle-aged participants (621 men and 431 women) who attended health screenings, and we analysed the intestinal microbiota using 16S rRNA gene sequencing. Relative muscle mass was calculated using a bioelectrical impedance analysis and presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/weight (kg) × 100]. We categorized the subjects into four groups by the quartile of the SMI. Association tests between gut microbiota and SMI were conducted according to the microbial diversity, taxonomic profiling and functional inference in a sex-stratified manner. RESULTS: The mean age and SMI of the total participants were 44.8 years (standard deviation [SD], 8.2) and 41.4% (SD, 3.9), respectively. After adjustments for possible covariates such as age, body mass index and regular physical activity, the highest quartile (Q4) group of SMI had higher alpha diversity than the lowest quartile (Q1) group in male participants (coefficient = 10.79, P < 0.05, linear regression model), whereas there was no difference in diversity among SMI groups in females. At the species level, Haemophilus parainfluenzae (coefficient = 1.910) and Roseburia faecis (coefficient = 1.536) were more abundant in the highest SMI (Q4) group than in the lowest SMI (Q1) group in males. However, no significant taxon was observed along the SMI groups in females. The gut microbiota of the lowest SMI group (Q1) was enriched with genes involved in biosynthesis of amino acids and energy generation compared with that of the highest SMI group (Q4) in both sexes, although the significance of the inferred pathways was weak (P < 0.05 but the false discovery rate q > 0.05). CONCLUSIONS: In this large sample of middle-aged individuals, this study highlights fundamental sex-specific differences in the microbial diversity, composition and metabolic pathways inferred from gut microbiota according to SMI. The gut microbiota may provide novel insights into the potential mechanisms underlying the sex dependence of skeletal muscle mass.

Comparison of methods for evaluation of upper esophageal sphincter (UES) relaxation duration: Videofluoroscopic swallow study versus high-resolution manometry.

This study aims to compare the 2 methods of upper esophageal sphincter (UES) relaxation measurement and determine which method has better diagnostic value in UES relaxation impairment The study included 140 patients with pharyngeal dysphagia who underwent both videofluoroscopic swallow study (VFSS) and high-resolution manometry (HRM). Feeding method was determined to oral or non-oral feeding based on the severity of dysphagia; 103 patients were in oral feeding group and 37 were in non-oral feeding group. UES relaxation duration was measured using VFSS and HRM, respectively. Receiver-operating characteristic curve analysis was conducted to validate the UES relaxation duration in determination of feeding method. UES relaxation duration was more decreased in non-oral feeding group than in oral feeding group on both VFSS and HRM. Receiver-operating characteristic analysis revealed that the optimal cutoff value of UES relaxation duration to determine feeding method (oral or non-oral feeding) was 0.42 seconds on VFSS and 0.44 seconds on HRM. The sensitivity for feeding method was higher in VFSS than HRM (83.5% vs 70.9%), while the specificity was higher in HRM than VFSS (48.6% vs 54.1%). VFSS and HRM have complementary ability in evaluating UES relaxation duration in patients with oropharyngeal dysphagia.

Impact of Low Skeletal Muscle Mass and Obesity on Hearing Loss in Asymptomatic Individuals: A Population-Based Study.

The relationship between low muscle mass (LMM) with obesity and hearing loss has been poorly studied. We aimed to investigate the association of LMM and obesity on hearing loss in the general population. A total of 265,792 adults who underwent a hearing test and body composition analyses were included. Pre-sarcopenia was defined as having an appendicular muscle mass index <5.7 kg/m2 for women and <7.0 kg/m2 for men, and obesity as a body mass index ≥25 kg/m2, while pre-sarcopenic obesity was defined as the co-presence of LMM and obesity. Participants were divided into four groups according to the presence of pre-sarcopenia and/or obesity. The prevalence of hearing loss was 1.8% in the control, 2.5% in the pre-sarcopenia alone, 3.0% in the obesity alone, and 6.2% in the pre-sarcopenic obesity group (p < 0.001). Hearing Thresholds were the highest in the pre-sarcopenic obesity group compared with the other three groups. In multivariable-adjusted models, the risk of hearing loss was the highest in the pre-sarcopenic obesity group (odds ratio: 1.30 [95% confidence interval: 1.10−1.56]), followed by the obesity alone (1.20 [1.12−1.28]) and pre-sarcopenia alone (1.19 [1.06−1.34]) group compared with the control group (p < 0.001). Pre-sarcopenic obesity was independently associated with a higher prevalence of hearing loss, supporting pre-sarcopenic obesity itself as a risk for the decline in hearing function.

Sex-Specific Associations between Serum Ferritin and Osteosarcopenic Obesity in Adults Aged over 50 Years.

We investigated the sex-specific association between ferritin and adverse body composition in adults aged over 50 years in a population-based cohort. A total of 25,546 participants (16,912 women; 8634 men) were stratified into three groups by the tertiles of ferritin. The number of adverse body compositions was categorized as 0 (without osteopenia/osteoporosis, low muscle mass, or obesity), 1 (having one of the components), 2 (two), and 3 (all three; osteosarcopenic obesity). As ferritin tertile increased, the prevalence of one, two, or three simultaneous adverse body compositions increased, significant only in women (p < 0.0001), not in men (p = 0.125). Among women, the prevalence of osteosarcopenic obesity gradually increased from 1.7% in the lowest, to 2.2% in the middle, and 2.5% in the highest tertile. Using multivariate-adjusted analysis, women in the higher tertile had an increased likelihood of having multiple adverse body compositions compared with those in the lowest tertile. Women in the highest tertile had a 1.52 times increased risk of osteosarcopenic obesity than those in the lowest tertile. A high ferritin level was associated with an increased risk of having multiple adverse body compositions, especially for osteosarcopenic obesity in women aged >50 years, suggesting its potential use for detecting osteosarcopenic obesity.

Sex Difference in Cutoff and Prevalence of Sarcopenia among 300,090 Urban Korean Population: Association with Metabolic Syndrome.

Background and Objectives: The study aimed to establish the threshold values and prevalence of sarcopenia and to investigate the association of sarcopenia with metabolic syndrome in an urban Korean population. Materials and Methods: The study included 300,090 adults who underwent anthropometric analyses by bioelectrical impedance analyzer. Sarcopenia was defined as: (1) class I, skeletal muscle mass index (SMI) within −1 to −2 standard deviations (SDs); (2) or class II, <−2 SD of SMI in a young population. Results: Low SMI threshold levels for class I and class II sarcopenia were 39.8 and 36.7% in men, and 35.5 and 32.3% in women. Among all age groups, the prevalence rates of sarcopenia were highest in the age group 80−89 years. Following adjustment for possible confounders including age, sex, height, metabolic and health behavioral factors, adjusted odds ratios (95% confidence intervals) for the risk of metabolic syndrome were 2.43 (2.33−2.54) for class I and 2.69 (2.49−2.91) for class II sarcopenia, compared with the normal reference. Sarcopenia was more strongly associated with metabolic syndrome in women than men (p for interaction < 0.01). The threshold values and prevalence of sarcopenia were demonstrated in a large Korean urban population. Conclusions: This study identified that sarcopenia was associated with increased risk of metabolic syndrome, showing itself to be significantly higher in women than men.

The effects of early exercise in traumatic brain-injured rats with changes in motor ability, brain tissue, and biomarkers.

Traumatic brain injury (TBI) is brain damage which is caused by the impact of external mechanical forces. TBI can lead to the temporary or permanent impairment of physical and cognitive abilities, resulting in abnormal behavior. We recently observed that a single session of early exercise in animals with TBI improved their behavioral performance in the absence of other cognitive abnormalities. In the present study, we investigated the therapeutic effects of continuous exercise during the early stages of TBI in rats. We found that continuous low-intensity exercise in early-stage improves the locomotion recovery in the TBI of animal models; however, it does not significantly enhance short-term memory capabilities. Moreover, continuous early exercise not only reduces the protein expression of cerebral damage-related markers, such as Glial Fibrillary Acid Protein (GFAP), Neuron-Specific Enolase (NSE), S100ß, Protein Gene Products 9.5 (PGP9.5), and Heat Shock Protein 70 (HSP70), but it also decreases the expression of apoptosis-related protein BAX and cleaved caspase 3. Furthermore, exercise training in animals with TBI decreases the microglia activation and the expression of inflammatory cytokines in the serum, such as CCL20, IL-13, IL-1α, and IL-1ß. These findings thus demonstrate that early exercise therapy for TBI may be an effective strategy in improving physiological function, and that serum protein levels are useful biomarkers for the predicition of the effectiveness of early exercise therapy.[BMB Reports 2022; 55(10): 506-511].

Increased Carcinoembryonic Antigen (CEA) Level Is Highly Associated with Low Skeletal Muscle Mass in Asymptomatic Adults: A Population-Based Study.

We investigated the relationship between high carcinoembryonic antigen (CEA) levels and low skeletal muscle mass (LMM) in asymptomatic adults in a population-based study. A total of 202,602 adults (mean age 41.7 years) without malignancy, stroke, cardiovascular disease, or chronic lung/liver disease were included. A high CEA level was defined as ≥5 ng/mL. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: "normal", "mild LMM", and "severe LMM." The prevalence of elevated CEA levels was the highest in subjects with severe LMM (4.2%), followed by those with mild LMM (1.6%) and normal muscle mass (1.1%) (p for trend < 0.001). In multivariate logistic regression analysis, high CEA was independently associated with having mild LMM (adjusted odds ratio, 1.139 [95% confidence interval, 1.092−1.188]) and severe LMM (2.611 [2.055−3.319]) compared to normal muscle mass. Furthermore, the association between high CEA and severe LMM was stronger in women than that in men (women, 5.373 [2.705−10.669]; men, 2.273 [1.762−2.933]). Elevated CEA levels were significantly associated with a higher prevalence of LMM. Therefore, increased CEA could be used as a biomarker for detecting LMM in adults without cancer.

A Comparison of the Effect of a 4.4-MHz Radiofrequency Deep Heating Therapy and Ultrasound on Low Back Pain: A Randomized, Double-Blind, Multicenter Trial.

Despite the increasing interest in RF (Radiofrequency) therapy, little is known about its effectiveness for low back pain (LBP). The aim of this study was to investigate the effectiveness of 4.4-MHz RF diathermy compared to ultrasound (US) in patients with LBP. One-hundred-and-eighteen patients with LBP were randomized with RF (n = 62) or US (n = 56). Investigator and subjects were blinded to the treatment group. Either RF (4.4 MHz, 45 W/cm2) or US (1 MHz, 2 W/cm2) was applied for 10 to 15 min, 3 times per week for 4 weeks. The primary outcome was the Oswestry Disability Index (ODI, %). Secondary outcomes were numeric rating scale (NRS), Biering−Sorensen test, up-and-go test, successful pain relief, and successful functional improvement. Clinical outcomes were evaluated prior to intervention (baseline), and at 4 and 12 weeks after treatment. There were no significant differences between the groups regarding baseline demographic and clinical characteristics. Both groups observed a significant improvement of ODI (%), NRS, Biering−Sorensen test, and up-and-go test at 4 and 12 weeks after treatment (p < 0.05); however, no significant differences were found between groups. The RF group showed a higher proportion of successful pain relief at 12 weeks after treatment than the US group (p = 0.048). The RF diathermy showed favorable results in pain reduction, improvement of function, mobility, and back muscle endurance. Compared with US, RF diathermy obtained slightly better perception of patients in pain relief at 12 weeks after treatment. The results from this study indicated that 4.4-MHz RF diathermy can effectively be used as a conservative treatment option for patients with LBP.

Relationship between hyperhomocysteinemia and coexisting obesity with low skeletal muscle mass in asymptomatic adult population.

The relationship between hyperhomocysteinemia (HHcy) and obesity with low skeletal muscle mass (LMM) has not been established. We aim to assess the association between HHcy and the coexistence of obesity and LMM in asymptomatic adult population. We conducted a population-based cross-sectional study among asymptomatic individuals who underwent measurements of plasma homocysteine and body composition analysis. HHcy was defined as > 15 umol/L, obesity as body mass index ≥ 25 (kg/m2), and LMM as skeletal muscle index less than 2 SD below the sex-specific mean of young adults. The participants were classified into 'control', 'obesity alone', 'LMM alone', and 'obesity with LMM'. Among 113,805 participants, the prevalence of HHcy was 8.3% in control, 8.7% in obesity alone, 10.0% in LMM alone, and 13.0% in obesity with LMM (p for trend < 0.001). In a multivariable logistic regression analysis, the associations showed a positive trend for HHcy along the groups from obesity alone, to LMM alone, and to obesity with LMM. HHcy was independently associated with the presence of LMM alone (adjusted odds ratio 1.186 [95% confidence interval 1.117-1.259]) and obesity with LMM (1.424 [1.134-1.788]), respectively. This study demonstrated that HHcys was more strongly associated with coexistence of obesity and LMM than either condition alone in the adult population.

Association between osteosarcopenia and coronary artery calcification in asymptomatic individuals.

Osteoporosis and sarcopenia are substantially interrelated with shared cardiovascular risk factors. However, the relationship between osteosarcopenia and coronary artery disease is largely unexplored. We aimed to investigate the association between osteosarcopenia and coronary artery calcification (CAC) scores in asymptomatic adults. A total of 5969 asymptomatic adults without cardiovascular disease who underwent a health examination including estimation of CAC scores by cardiac tomography were analyzed. Osteoporosis was defined as low bone mineral density T-score ≤ - 2.5 standard deviation, and sarcopenia as appendicular skeletal muscle mass < 5.7 kg/m2 for women and < 7.0 kg/m2 for men, and osteosarcopenia as the copresence of both osteoporosis and sarcopenia. Participants were divided into four groups according to the presence of osteoporosis and/or sarcopenia as control, sarcopenia alone, osteoporosis alone, and osteosarcopenia. Prevalence of CAC was 22.0% in control, 23.6% in sarcopenia alone, 38.5% in osteoporosis alone, and 48.3% in osteosarcopenia group, with the osteosarcopenia group showing the highest (p < 0.0001). After adjustments for possible confounders, mean of log (CAC score + 1) in osteosarcopenia group was higher than other three groups (Bonferroni p < 0.0001). Using multivariate-adjusted analysis, subjects with osteosarcopenia had the highest risk for having CAC > 0 (odds ratio [OR] 2.868; 95% confidence interval [CI] 1.717-4.790). Furthermore, subjects with osteosarcopenia had a significant risk of moderate-to-extensive CAC (CAC score ≥ 100) (OR 2.709; 95% CI 1.128-6.505). We demonstrated that osteosarcopenia was independently associated with a higher prevalence of subclinical coronary atherosclerosis. Our results suggest osteosarcopenia as a predisposing factor for coronary heart disease.

Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults.

BACKGROUND: Homocysteine has been drawing attention with a closed linkage with skeletal muscle. However, the association of hyperhomocysteinemia with decreased skeletal muscle mass remains unclear. We aimed to investigate the association of hyperhomocysteinemia with low skeletal muscle mass (LMM) in asymptomatic adults. METHODS: This was a cross-sectional study of 114,583 community-dwelling adults without cancer, stroke, or cardiovascular diseases who underwent measurements of plasma homocysteine and body composition analysis from 2012 to 2018. Hyperhomocysteinemia was defined as >15 µmol/L. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: "normal," "mildly low," and "severely low." RESULTS: The prevalence of hyperhomocysteinemia was the highest in subjects with severely LMM (12.9%), followed by those with mildly LMM (9.8%), and those with normal muscle mass (8.5%) (P for trend <0.001). In a multivariable logistic regression model, hyperhomocysteinemia was significantly associated with having a mildly LMM (odds ratio [OR], 1.305; 95% confidence interval [CI], 1.224 to 1.392) and severely LMM (OR, 1.958; 95% CI, 1.667 to 2.286), respectively. One unit increment of log-transformed homocysteine was associated with 1.360 and 2.169 times higher risk of having mildly LMM and severely LMM, respectively. CONCLUSION: We demonstrated that elevated homocysteine has an independent association with LMM in asymptomatic adults, supporting that hyperhomocysteinemia itself can be a risk for decline in skeletal musculature.

Prevalence and Related Factors for Poststroke Complex Regional Pain Syndrome: A Retrospective Cross-Sectional Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the prevalence of poststroke complex regional pain syndrome (CRPS) to estimate related factors for poststroke CRPS in patients with first-ever stroke. DESIGN: This was a retrospective cross-sectional cohort study of adult patients (age >18y) with stroke who were admitted to rehabilitation unit from December 2014 to May 2018 in Korea. SETTING: Single acute rehabilitation unit of university hospital. PARTICIPANTS: Participants (N=313) diagnosed with first-ever stroke were identified from the stroke rehabilitation registry of our institute. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of poststroke CRPS based on clinical features and 3-phase bone scintigraphy and the related factors of poststroke CRPS. RESULTS: A total of 313 records were analyzed, including demographic, clinical characteristics, and functional variables. Poststroke CRPS was found in 8.94% (28 of 313) patients with first-ever stroke. Logistic regression analysis showed that Fugl Meyer Assessment of Upper Extremity (FMA-UE) score was a significant associated factor for the presence of CRPS (odds ratio, 0.96; 95% confidence interval, 0.94-0.98; P=.003). The cutoff value of 76 points for FMA-UE score yielded moderate accuracy in identifying of poststroke CRPS (92.6% sensitivity, 65.8% specificity, and 0.85 area under the curve). CONCLUSIONS: The prevalence of poststroke CRPS was 8.94% in patients with first-ever stroke. The FMA-UE score was associated with the poststroke CRPS. Therefore, in patients with low FMA-UE score, prevention and high suspicion of post-stroke CRPS is necessary.

Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor.

The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.

The Diagnostic Significance of Ultrasonographic Measurement of the Achilles Tendon Thickness for the Insertional Achilles Tendinopathy in Patients with Heel Pain.

No consensus exists concerning the diagnostic role or cutoff value of the Achilles tendon thickness on ultrasonography (US) for the diagnosis of insertional Achilles tendinopathy. This study sought to assess the diagnostic utility of US measurement of the thickness and echogenicity of the Achilles tendon for the insertional Achilles tendinopathy in patients with heel pain, and to compare the results with those of the plantar fascia for the plantar fasciitis. We conducted US examinations in consecutive patients who presented with unilateral or bilateral heel pain at the foot clinic of a single tertiary hospital from February 2016 to December 2020. Each US evaluation assessed the thickness and echogenicity of the insertion area of the Achilles tendon and plantar fascia. We retrospectively compared these parameters between patients with insertional Achilles tendinopathy or plantar fasciitis and normal controls and analyzed the diagnostic utility of these parameters. Based on clinical diagnosis, 44 feet were diagnosed with insertional Achilles tendinopathy, 109 feet were diagnosed with plantar fasciitis, and 32 feet were classified as normal. There was a significant difference in the thickness of the plantar fascia between the plantar fasciitis and normal control groups (p = 0.032). There was also a significant difference in the echogenicity of the plantar fascia between the plantar fasciitis and normal groups (p < 0.001). However, there was no significant difference in the thickness of the insertional area of the Achilles tendon between the insertional Achilles tendinopathy and normal groups (p = 0.132). There was a significant difference in the echogenicity of the insertional area of the Achilles tendon between the insertional Achilles tendinopathy and normal groups (p < 0.001). US measurement of the thickness of the insertional area of the Achilles tendon might not reflect the clinical status of insertional Achilles tendinopathy, unlike that of plantar fasciitis.

Correlation of Ultrasound Findings With Clinical Stages and Impairment in Adhesive Capsulitis of the Shoulder.

BACKGROUND: Ultrasound is an essential tool for diagnosing shoulder disorders. However, the role of ultrasound in assessing and diagnosing adhesive capsulitis has not been fully studied. PURPOSE: To evaluate the ultrasound features of adhesive capsulitis and estimate the correlations between clinical impairment and ultrasound parameters. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 61 patients with clinically diagnosed unilateral adhesive capsulitis were retrospectively reviewed using high-resolution ultrasound. To compare ultrasound parameters, we performed ultrasound examinations on both affected and unaffected shoulders. Ultrasound parameters, including thickness of the coracohumeral ligament (CHL), rotator interval (RI), axillary recess (AR), hypervascularity of the RI, and effusion of the long head of the biceps tendon sheath, were measured. Passive range of motion (PROM), visual analog scale for pain, and the Shoulder Pain and Disability Index were used for clinical assessment. RESULTS: The CHL, the RI, and the AR in affected shoulders were significantly thicker than in unaffected shoulders (P < .05). CHL thickness in affected shoulders was significantly correlated with PROM limitation, which included forward elevation, abduction, external rotation (ER), and internal rotation (IR) (P < .05). AR thickness correlated with passive forward elevation limitation and passive IR limitation (P < .05). The CHL was significantly thicker in stage 2 compared with stage 1, and the RI was thicker in stage 2 compared with stage 3. The diagnostic cutoff values for adhesive capsulitis were 2.2 mm for CHL thickness (77% sensitivity, 91.8% specificity) and 4 mm for AR thickness (68.9% sensitivity, 90.2% specificity). CONCLUSION: The ultrasound parameters associated with structural changes were correlated with clinical characteristics of adhesive capsulitis. Thickened CHL, RI, and AR were observed in affected shoulders. The cutoff values of 2.2 mm for CHL thickness and 4 mm for AR thickness can be used as cutoff diagnostic values for adhesive capsulitis.

Variants in NEB and RIF1 genes on chr2q23 are associated with skeletal muscle index in Koreans: genome-wide association study.

Although skeletal muscle plays a crucial role in metabolism and influences aging and chronic diseases, little is known about the genetic variations with skeletal muscle, especially in the Asian population. We performed a genome-wide association study in 2,046 participants drawn from a population-based study. Appendicular skeletal muscle mass was estimated based on appendicular lean soft tissue measured with a multi-frequency bioelectrical impedance analyzer and divided by height squared to derive the skeletal muscle index (SMI). After conducting quality control and imputing the genotypes, we analyzed 6,391,983 autosomal SNPs. A genome-wide significant association was found for the intronic variant rs138684936 in the NEB and RIF1 genes (ß = 0.217, p = 6.83 × 10-9). These two genes are next to each other and are partially overlapped on chr2q23. We conducted extensive functional annotations to gain insight into the directional biological implication of significant genetic variants. A gene-based analysis identified the significant TNFSF9 gene and confirmed the suggestive association of the NEB gene. Pathway analyses showed the significant association of regulation of multicellular organism growth gene-set and the suggestive associations of pathways related to skeletal system development or skeleton morphogenesis with SMI. In conclusion, we identified a new genetic locus on chromosome 2 for SMI with genome-wide significance. These results enhance the biological understanding of skeletal muscle mass and provide specific leads for functional experiments.

The prospective relationship between low muscle mass and thyroid hormones among 198 069 euthyroid men and women; comparing different definitions of low muscle mass.

OBJECTIVE: The impact of thyroid hormones within normal range on muscle mass remains unknown. We examined the association between new onset of low muscle mass (LMM) and thyroid hormones among euthyroid men and women with three different definitions of LMM in prospective cohort study. METHODS: We performed a cohort study of 198 069 Korean adults (mean age of 39.2 years), free of LMM at baseline, who participated in a repeated screening examination and were followed up annually or biennially for up to 6.3 years. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by an electrochemiluminescent immunoassay. Muscle mass was assessed using a bioelectrical impedance analyser. LMM was defined as the appendicular skeletal muscle mass (ASM) by body weight (ASM/weight, LMM-W), height squared (ASM/height2 , LMM-H) and BMI (ASM/BMI, LMM-B) of one standard deviation below the sex-specific mean for young reference group. RESULTS: During a median follow-up of 3.1 years (interquartile range, 2.0-4.1 years), new-onset LMM-W, LMM-H and LMM-B occurred in 17 856 (incident rate, 27.8 per 1000 person-years), 8307 (incident rate, 13.4 per 1000 person-years) and 13 990 participants (incident rate, 24.5 per 1000 person-years) in each. In euthyroid men, FT4 was inversely and FT3 positively associated with incident LMM-W in a dose-response manner. TSH and FT4 had inverse dose-response relationship with incident LMM-B. Incident LMM-H of euthyroid men has no apparent associations with any thyroid hormones. Euthyroid women had no dose-response relationship between thyroid hormones and any definition of LMM. CONCLUSIONS: Among euthyroid men, FT4 had inverse dose-response association with new onset of LMM defined with weight (LMM-W) and BMI (LMM-B). Height squared LMM (LMM-H) had no apparent relationship with any thyroid hormones. Euthyroid women had no dose-responsive association between thyroid hormones and incident LMM.