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Background Methods that facilitate muscle quality measurement may improve the diagnosis of sarcopenia. Current research has focused on the phase angle (PhA) obtained through bioelectrical impedance analysis (BIA) as an indicator of cellular health, particularly cell membrane integrity and cell function. The current study therefore aimed to evaluate the relationship between the PhA and muscle quality and muscle‐related parameters and to determine factors associated with the PhA. Moreover, we attempted to determine the cut‐off value of PhA for predicting sarcopenia. Methods First‐year university students (830 male students, 18.5 ± 0.6 years old; 422 female students, 18.3 ± 0.5 years old) and community‐dwelling elderly individuals (70 male individuals, 74.4 ± 5.5 years old; 97 female individuals, 73.1 ± 6.4 years old) were included. PhA and other body composition data were measured using BIA, while muscle quality was calculated by dividing handgrip strength by upper limbs muscle mass. The relationship between PhA and the aforementioned parameters were then analysed, after which the cut‐off value of PhA for predicting sarcopenia was examined. Results Multiple linear regression analysis revealed that age, skeletal muscle mass index (SMI), and muscle quality were independently associated with PhA in both sexes [male (age: standardized regression coefficient (β) = −0.43, P < 0.001, SMI: β = 0.61, P < 0.001, muscle quality: β = 0.13, P < 0.001) and female (age: β = −0.56, P < 0.001, SMI: β = 0.52, P < 0.001, muscle quality: β = 0.09, P = 0.007)]. Participants with sarcopenia had a significantly lower PhA compared with those without it (sarcopenia vs. non‐sarcopenia: young male participants, 5.51 ± 0.41° vs. 6.25 ± 0.50°, P < 0.001; young female participants, 4.88 ± 0.16° vs. 5.37 ± 0.44°, P = 0.005; elderly female participants: 4.14 ± 0.29° vs. 4.63 ± 0.42°, P = 0.009). Although no significant findings were observed in elderly male participants, the same tendency was noted. Receiver operating characteristic (ROC) curve analysis indicated that PhA had good predictive ability for sarcopenia in young male, elderly male, young female, and elderly female participants (area under the ROC curve of 0.882, 0.838, 0.865, and 0.850, with cut‐off PhA values of 5.95°, 5.04°, 5.02°, and 4.20° for predicting sarcopenia, respectively). Conclusions The PhA reflected muscle quality and exhibited good accuracy in detecting sarcopenia, suggesting its utility as an index for easily measuring muscle quality, which could improve the diagnosis of sarcopenia.

General muscle health declines with age, and in particular, sarcopenia—defined as progressive loss of muscle mass and strength/physical performance—is a growing issue in Asia with a rising population of community‐dwelling older adults. Several guidelines have addressed early identification of sarcopenia and management, and although nutrition is central to treatment of sarcopenia, there are currently few guidelines that have examined this specifically in the Asian population. Therefore, the Asian Working Group for Sarcopenia established a special interest group (SIG) comprising seven experts across Asia and one from Australia, to develop an evidence‐based expert consensus. A systematic literature search was conducted using MEDLINE on the topic of muscle health, from 2016 (inclusive) to July 2021, in Asia or with relevance to healthy, Asian community‐dwelling older adults (≥60 years old). Several key topics were identified: (1) nutritional status: malnutrition and screening; (2) diet and dietary factors; (3) nutritional supplementation; (4) lifestyle interventions plus nutrition; and (5) outcomes and assessment. Clinical questions were developed around these topics, leading to 14 consensus statements. Consensus was achieved using the modified Delphi method with two rounds of voting. Moreover, the consensus addressed the impacts of COVID‐19 on nutrition, muscle health, and sarcopenia in Asia. These statements encompass clinical expertise and knowledge across Asia and are aligned with findings in the current literature, to provide a practical framework for addressing muscle health in the community, with the overall aim to encourage and facilitate broader access to equitable care for this target population.

Background There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community‐dwelling older adults. Methods We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check‐ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi‐frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all‐cause mortality and incident disability. Results The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia‐related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P‐values <0.05) among men and cognitive impairment (P = 0.004) and depressed mood (P < 0.001) among women. Individuals with sarcopenia had higher risks of mortality [hazard ratios (95% confidence interval): 2.0 (1.2–3.5) in men and 2.3 (1.1–4.9) in women] and incident disability [1.6 (1.0–2.7) in men and 1.7 (1.1–2.7) in women]. Compared with the individuals without any sarcopenia components, those having low grip strength and/or slow gait speed without low ALMI tended to have an increased risk of disability [1.4 (1.0–2.0), P = 0.087], but not mortality [1.3 (0.8–2.2)]. We did not find increased risks of these outcomes in participants having low ALMI in the absence of low grip strength and slow gait speed [1.2 (0.8–1.9) for mortality and 0.9 (0.6–1.3) for incident disability]. Conclusions Japanese older men and women meeting Asian criteria of sarcopenia had increased risks of all‐cause mortality and disability. There were no significant increased risks of death or incident disability for both participants with muscle weakness and/or low performance without low muscle mass and those with low muscle mass with neither muscle weakness nor low performance. Further studies are needed to examine the interaction between muscle loss, muscle weakness, and low performance for adverse health‐related outcomes.

Background The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. Methods Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1996 and 2015 in five hospitals by analyzing their baseline clinical features, laboratory, imaging, and pathological test findings, and treatment. Results Of the 334 patients listed, 205 were male and median age at diagnosis was 65 years. The mean number of organs involved was 3.2 at diagnosis. The most frequently affected organs were the salivary glands, followed by the lacrimal glands, lymph nodes, pancreas, retroperitoneum/periaorta, kidneys, and lungs. The mean serum level of IgG4 was 755 mg/dl, and more than 95% of patients had elevated serum IgG4 levels. The median serum level of C-reactive protein (CRP) was 0.1 mg/dl and the level was less than 1 mg/dl in 90% of patients. A total of 34.7% of patients had low serum levels of C3. Serum levels of C3 and non-IgG4 IgG, calculated as the total IgG minus IgG4, showed an inverse correlation in patients with kidney lesions, while serum IgG4 levels were not correlated with serum C3 levels. Corticosteroid was administered in 78.0% of patients, and was effective in all. Conclusions The serum CRP level is generally low and the serum IgG4 level is elevated in most Japanese IgG4-RD patients, in contrast to western patients. These original findings suggest that these two parameters in IgG4-RD differ in some interesting ways from those hitherto reported in western populations. Additional studies, especially international comparative ones, are needed to elucidate the extent and significance of these differences between populations. Attention will also have to be paid to whether the existence of such differences requires consideration when devising international classification criteria.

Background Skeletal muscle is mainly responsible for insulin‐stimulated glucose disposal. Dysfunction in skeletal muscle metabolism especially during obesity contributes to the insulin resistance. Astaxanthin (AX), a natural antioxidant, has been shown to ameliorate hepatic insulin resistance in obese mice. However, its effects in skeletal muscle are poorly understood. The current study aimed to investigate the molecular target of AX in ameliorating skeletal muscle insulin resistance. Methods We fed 6‐week‐old male C57BL/6J mice with normal chow (NC) or NC supplemented with AX (NC+AX) and high‐fat‐diet (HFD) or HFD supplemented with AX for 24 weeks. We determined the effect of AX on various parameters including insulin sensitivity, glucose uptake, inflammation, kinase signaling, gene expression, and mitochondrial function in muscle. We also determined energy metabolism in intact C2C12 cells treated with AX using the Seahorse XFe96 Extracellular Flux Analyzer and assessed the effect of AX on mitochondrial oxidative phosphorylation and mitochondrial biogenesis. Results AX‐treated HFD mice showed improved metabolic status with significant reduction in blood glucose, serum total triglycerides, and cholesterol (p< 0.05). AX‐treated HFD mice also showed improved glucose metabolism by enhancing glucose incorporation into peripheral target tissues, such as the skeletal muscle, rather than by suppressing gluconeogenesis in the liver as shown by hyperinsulinemic–euglycemic clamp study. AX activated AMPK in the skeletal muscle of the HFD mice and upregulated the expressions of transcriptional factors and coactivator, thereby inducing mitochondrial remodeling, including increased mitochondrial oxidative phosphorylation component and free fatty acid metabolism. We also assessed the effects of AX on mitochondrial biogenesis in the siRNA‐mediated AMPK‐depleted C2C12 cells and showed that the effect of AX was lost in the genetically AMPK‐depleted C2C12 cells. Collectively, AX treatment (i) significantly ameliorated insulin resistance and glucose intolerance through regulation of AMPK activation in the muscle, (ii) stimulated mitochondrial biogenesis in the muscle, (iii) enhanced exercise tolerance and exercise‐induced fatty acid metabolism, and (iv) exerted antiinflammatory effects via its antioxidant activity in adipose tissue. Conclusions We concluded that AX treatment stimulated mitochondrial biogenesis and significantly ameliorated insulin resistance through activation of AMPK pathway in the skeletal muscle.

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three‐round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C‐reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3–6 month period and suggested a tentative cut‐off value of 21 kg/m 2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ‐5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient‐reported outcomes. The AWGC consensus offers a comprehensive definition and user‐friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co‐morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Background Sarcopenia is an important prognostic factor of lung cancer. The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI, serum creatinine × cystatin C‐based glomerular filtration rate) are novel screening tools for sarcopenia; however, the diagnostic accuracy of the CCR and SI for detecting sarcopenia remains unknown. We aimed to explore and validate the diagnostic values of the CCR and SI for determining sarcopenia in non‐small cell lung cancer (NSCLC) and to explore their prognostic values for overall survival. Methods We conducted a prospective cohort study of adult patients with stage IIIB or IV NSCLC. Levels of serum creatinine and cystatin C were measured to calculate the CCR and SI. Sarcopenia was defined separately using CCR, SI, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Participants were randomly sampled into derivation and validation sets (6:4 ratio). The cutoff values for diagnosing sarcopenia were determined based on the derivation set. Diagnostic accuracy was analysed in the validation set through receiver operating characteristic (ROC) curves. Cox regression models and survival curves were applied to evaluate the impact of different sarcopenia definitions on survival. Results We included 579 participants (women, 35.4%; mean age, 58.4 ± 8.9 years); AWGS‐defined sarcopenia was found in 19.5% of men and 10.7% of women. Both CCR and SI positively correlated with computed tomography‐derived and bioimpedance‐derived muscle mass and handgrip strength. The optimal cutoff values for CCR and SI were 0.623 and 54.335 in men and 0.600 and 51.742 in women, with areas under the ROC curves of 0.837 [95% confidence interval (CI): 0.770–0.904] and 0.833 (95% CI: 0.765–0.901) in men (P = 0.25), and 0.808 (95% CI: 0.682–0.935) and 0.796 (95% CI: 0.668–0.924) in women (P = 0.11), respectively. The CCR achieved sensitivities and specificities of 73.0% and 93.7% in men and 85.7% and 65.7% in women, respectively; the SI achieved sensitivities and specificities of 75.7% and 86.5% in men and 92.9% and 62.9% in women, respectively. CCR‐defined, SI‐defined, and AWGS‐defined sarcopenia were independently associated with a high mortality risk [hazard ratio (HR) = 1.75, 95% CI: 1.25–2.44; HR = 1.55, 95% CI: 1.11–2.17; and HR = 1.76, 95% CI: 1.22–2.53, respectively]. Conclusions CCR and SI have satisfactory and comparable diagnostic accuracy and prognostic values for sarcopenia in patients with advanced NSCLC. Both may serve as surrogate biomarkers for evaluating sarcopenia in these patients. However, further external validations are required.

Background Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse. Methods Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16 s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant. Results Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation. Conclusion Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.