Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Comment on ‘Association of Computed Tomography‐Derived Body Composition and Complications After Colorectal Cancer Surgery: A Systematic Review and Meta‐Analysis’ by Van Helsdingen et al.","authors":"Rachana Mehta, Ashok Kumar Balaraman, Muhammed Shabil, Sanjit Sah","doi":"10.1002/jcsm.13679","DOIUrl":"https://doi.org/10.1002/jcsm.13679","url":null,"abstract":"<p>We read with great interest the article titled ‘Association of computed tomography-derived body composition and complications after colorectal cancer surgery A systematic review and meta-analysis’ and commend the authors for their rigorous and insightful systematic review and meta-analysis on body composition measurements using computed tomography (CT) scans as predictors of complications following colorectal cancer surgery [<span>1</span>]. This research addresses a highly relevant clinical issue, providing valuable information to guide surgical decision-making. While the article provides important findings, we believe there are some additional aspects that could further strengthen its impact and provide readers with an even more comprehensive understanding.</p>\u0000<p>First, although the authors conducted a thorough risk of bias assessment using the QUIPS tool, the article does not mention whether a sensitivity analysis was performed based on study quality. We suggest conducting such an analysis to examine how excluding lower-quality studies (e.g., those rated as having a high risk of bias) may impact the pooled results. Sensitivity analysis could help readers better appreciate the robustness of the findings and determine whether the conclusions are consistent across studies with varying levels of methodological rigour [<span>2</span>].</p>\u0000<p>Second, the certainty of evidence presented in this study could have been evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework. GRADE is widely recognized for systematically assessing the quality of evidence and the strength of recommendations in health care research. Including a GRADE assessment would allow the readers to understand the confidence in the results across different outcomes, especially given the variability in CT measurement methods and clinical endpoints considered in the studies [<span>3</span>]. This would also facilitate the translation of evidence into clinical practice by offering clarity on the reliability of the conclusions.</p>\u0000<p>Third, while the authors rightfully address the risk of publication bias in the discussion, we recommend the inclusion of formal statistical methods to assess this risk. A funnel plot or DOI plot, alongside statistical tests such as Egger's regression or the trim-and-fill method, could provide more concrete evidence of the presence or absence of publication bias [<span>4</span>]. These methods would further substantiate the robustness of the meta-analytic findings by ensuring that the results were not disproportionately influenced by small or positive-result studies.</p>\u0000<p>Furthermore, it might be valuable to explore subgroup analyses based on factors such as the specific CT measurement (e.g., visceral fat vs. sarcopenia), patient age, or cancer stage. These analyses could uncover potential variations in predictive utility across different patient populations, making the results more clinically actionab","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"41 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT‐Based Body Composition and Frailty as Predictors of Survival Among Older Adults With Gastrointestinal Malignancies","authors":"Smith Giri, Christian Harmon, Daniel Hess, Elizabeth M. Cespedes Feliciano, Ijeamaka Anyene Fumagalli, Bette Caan, Leon Lenchik, Karteek Popuri, Vincent Chow, Mirza Faisal Beg, Smita Bhatia, Grant R. Williams","doi":"10.1002/jcsm.13664","DOIUrl":"https://doi.org/10.1002/jcsm.13664","url":null,"abstract":"BackgroundOlder adults with cancer are at an increased risk of treatment related toxicities and early death. Routinely collected clinico‐demographic characteristics inadequately explain this increased risk limiting accurate prognostication. Prior studies have suggested that altered body composition and frailty are independently associated with worse survival among older adults with cancer; however, their combined influence remains unclear.MethodsWe used data from a single‐institution prospective cohort study of older adults (≥ 60 years) who underwent geriatric assessment (GA) at the time of initial consultation with a medical oncologist from September 2017 to December 2020 and available baseline abdominal computed tomography within 60 days of GA. Using multi‐slice CT images from T12 to L5 level, we assessed volumetric measures of skeletal muscle (SMV), visceral adipose tissue (VATV), subcutaneous adipose tissue (SATV) and averaged skeletal muscle density (SMD), computing sex‐specific <jats:italic>z</jats:italic> for each measure. Frailty was measured using a 44‐item frailty index using the deficit accumulation approach. Primary outcome of interest was overall survival (OS) defined as time from GA to death or last follow up. We used multivariable Cox regression model to study the independent association between the above four body composition measurements and OS adjusted for baseline confounders and frailty.ResultsWe included 459 patients with a mean age of 69.7 ± 7.5 years, 60% males and 77% non‐Hispanic Whites. Most had colorectal (27%) or pancreatic cancer (20%) and 48% had stage IV disease. Over a median follow up of 39.4 months, 209 patients (46%) died. In multivariable Cox regression models adjusted for age, sex, race, cancer type, cancer stage and frailty, skeletal muscle volume (HR 0.74; 95% CI 0.58–0.96; <jats:italic>p</jats:italic> = 0.02, per 1 SD increment) was independently associated with OS. The addition of body composition variables to baseline clinico‐demographic variables and frailty led to a slightly improved model discrimination.ConclusionsSMV is independently associated with OS among older adults with newly diagnosed gastrointestinal cancers. Capturing body composition measurements in oncology practice may provide additional prognostic information for older adults with cancer above and beyond what is captured in routine clinical assessment including frailty.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"92 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Association Between Dynapenic Obesity and Risk of Cardiovascular Disease: The Hisayama Study’ by Setoyama et al.","authors":"Chang Liu, Fan Zhang, Min Cao","doi":"10.1002/jcsm.13684","DOIUrl":"https://doi.org/10.1002/jcsm.13684","url":null,"abstract":"&lt;p&gt;We have read with interest the article by Setoyama Y et al. [&lt;span&gt;1&lt;/span&gt;] titled ‘Association of dynapenic obesity with cardiovascular disease: The Hisayama Study.’ While this study provides valuable insights into the relationship between dynapenic obesity and cardiovascular disease risk, we would like to highlight three points that warrant further discussion.&lt;/p&gt;\u0000&lt;p&gt;First, the authors introduce the concept of ‘dynapenic obesity’ and discuss it alongside ‘sarcopenic obesity’ in the introduction, citing multiple references related to sarcopenic obesity. However, according to the 2022 guidelines from the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), sarcopenic obesity is specifically defined as the coexistence of obesity and sarcopenia [&lt;span&gt;2&lt;/span&gt;]. In Setoyama et al.'s study, dynapenic obesity only considers handgrip strength and body mass index, whereas handgrip strength is just one dimension of assessing sarcopenia and cannot fully represent a sarcopenia diagnosis [&lt;span&gt;3&lt;/span&gt;]. Therefore, the authors should not equate dynapenic obesity with sarcopenic obesity. This conceptual confusion may lead to misinterpretation and misapplication of the study results.&lt;/p&gt;\u0000&lt;p&gt;Second, this study not only spans a median follow-up of 24 years but also assesses baseline handgrip strength and body mass index. Over such an extended follow-up period, important variables such as participants' physical function, height, weight, dietary habits, and physical activity are likely to have changed significantly. These changes would inevitably affect the association between exposure and outcome, and we consider this crucial limitation should be emphasized more strongly, with a discussion of its potential impact on the study findings.&lt;/p&gt;\u0000&lt;p&gt;Third, from a statistical perspective, the study uses Cox proportional hazards models to analyse the relationship between dynapenic obesity and cardiovascular disease risk. However, given the long-term nature of the follow-up, the proportional hazards assumption may not hold. The impact of dynapenic obesity on cardiovascular disease risk might change over time. Therefore, we suggest that the authors consider using time-dependent Cox models or other statistical methods suitable for long-term follow-up data to more accurately capture the time-varying relationship between exposure and outcome [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Additionally, the study employs multiple comparisons but does not appear to have applied any correction for multiple testing. This could increase the risk of Type I errors, leading to false-positive results. We recommend that the authors consider using appropriate methods for multiple comparison correction, such as the Bonferroni correction or false discovery rate methods [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;In conclusion, while Setoyama et al.'s study provides important insights into the relationship between dynapenic obesity and cardiovascular dis","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"4 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaperone Proteins: The Rising Players in Muscle Atrophy","authors":"Davide Acquarone, Alessandro Bertero, Mara Brancaccio, Matteo Sorge","doi":"10.1002/jcsm.13659","DOIUrl":"https://doi.org/10.1002/jcsm.13659","url":null,"abstract":"Despite significant progress in understanding the molecular aetiology of muscle atrophy, there is still a great need for new targets and drugs capable of counteracting muscle wasting. The role of an impaired proteostasis as the underlying causal mechanism of muscle atrophy is a well‐established concept. From the earliest work on muscle atrophy and the identification of the first atrogenes, the hyper‐activation of the proteolytic systems, such as autophagy and the ubiquitin proteasome system, has been recognized as the major driver of atrophy. However, the role of other key regulators of proteostasis, the chaperone proteins, has been largely overlooked. Chaperone proteins play a pivotal role in protein folding and in preventing the aggregation of misfolded proteins. Indeed, some chaperones, such as αB‐crystallin and Hsp25, are involved in compensatory responses aimed at counteracting protein aggregation during sarcopenia. Chaperones also regulate different intracellular signalling pathways crucial for atrogene expression and the control of protein catabolism, such as the AKT and NF‐kB pathways, which are regulated by Hsp70 and Hsp90. Furthermore, the downregulation of certain chaperones causes severe muscle wasting per se and experimental strategies aimed at preventing this downregulation have shown promising results in mitigating or reversing muscle atrophy. This highlights the therapeutic potential of targeting chaperones and confirms their crucial anti‐atrophic functions. In this review, we summarize the most relevant data showing the modulation and the causative role of chaperone proteins in different types of skeletal muscle atrophies.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"22 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Sarcopenia: Systematic Review and Meta‐Analysis on Its Incidence and Muscle Parameter Shifts During Hospitalisation","authors":"Luke Aldrich, Theocharis Ispoglou, Konstantinos Prokopidis, Jasem Alqallaf, Oliver Wilson, Antonis Stavropoulos‐Kalinoglou","doi":"10.1002/jcsm.13662","DOIUrl":"https://doi.org/10.1002/jcsm.13662","url":null,"abstract":"BackgroundAcute sarcopenia is sarcopenia lasting less than 6 months, typically following acute illness or injury. It may impact patient recovery and quality of life, advancing to chronic sarcopenia. However, its development and assessment remain poorly understood, particularly during hospitalisation. This systematic review aimed to elucidate the incidence of acute sarcopenia and examine changes in muscle parameters during hospitalisation.MethodsEighty‐eight papers were included in the narrative synthesis; 33 provided data for meta‐analyses on the effects of hospitalisation on handgrip strength (HGS), rectus femoris cross‐sectional area (RFCSA) and various muscle function tests. Meta‐regressions were performed for length of hospital stay (LoS) and age for all meta‐analyses; sex was also considered for HGS.ResultsAcute sarcopenia development was assessed in four studies with a pooled incidence of 18% during hospitalisation. Incidence was highest among trauma patients in intensive care (59%), whereas it was lower among medical and surgical patients (15%–20%). Time of development ranged from 4 to 44 days. HGS remained stable during hospitalisation (SMD = 0.05, 95% CI = −0.18:0.28, <jats:italic>p</jats:italic> = 0.67) as did knee extensor strength. LoS affected HGS performance (θ = 0.04, 95% CI = 0.001:0.09, <jats:italic>p</jats:italic> = 0.045) but age (<jats:italic>p</jats:italic> = 0.903) and sex (<jats:italic>p</jats:italic> = 0.434) did not. RFCSA, reduced by 16.5% over 3–21 days (SMD = −0.67, 95% CI = −0.92:−0.43, <jats:italic>p</jats:italic> &lt; 0.001); LoS or time between scans did significantly predict the reduction (θ = −0.04, 95% CI = −0.077:−0.011, <jats:italic>p</jats:italic> = 0.012). Indices of muscle quality also reduced. Muscle function improved when assessed by the short physical performance battery (SMD = 0.86, 95% CI = 0.03:1.69, <jats:italic>p</jats:italic> = 0.046); there was no change in 6‐min walk (<jats:italic>p</jats:italic> = 0.22), timed up‐and‐go (<jats:italic>p</jats:italic> = 0.46) or gait speed tests (<jats:italic>p</jats:italic> = 0.98). The only significant predictor of timed up‐and‐go performance was age (θ = −0.11, 95% CI = −0.018:−0.005, <jats:italic>p</jats:italic> = 0.009).ConclusionsAssessment and understanding of acute sarcopenia in clinical settings are limited. Incidence varies between clinical conditions, and muscle parameters are affected differently. HGS and muscle function tests may not be sensitive enough to identify acute changes during hospitalisation. Currently, muscle health deterioration may be underdiagnosed impacting recovery, quality of life and overall health following hospitalisation. Further evaluation is necessary to determine the suitability of existing diagnostic criteria of acute sarcopenia. Muscle mass and quality indices might need to become the primary determinants for muscle health assessment in hospitalised populations.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"78 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lonafarnib Protects Against Muscle Atrophy Induced by Dexamethasone","authors":"Sanghoon Bae, Van-Hieu Mai, Seyoung Mun, Dalong Dong, Kyudong Han, Sunghyouk Park, Jung Keun Hyun","doi":"10.1002/jcsm.13665","DOIUrl":"https://doi.org/10.1002/jcsm.13665","url":null,"abstract":"Muscle atrophy, including glucocorticoid-induced muscle wasting from treatments such as dexamethasone (DEX), results in significant reductions in muscle mass, strength and function. This study investigates the potential of lonafarnib, a farnesyltransferase inhibitor, to counteract DEX-induced muscle atrophy by targeting key signalling pathways.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"25 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Skeletal Muscle Radiodensity Predicts Response to CDK4/6 Inhibitors Plus Aromatase Inhibitors in Advanced Breast Cancer","authors":"Hyunwook Kim, Seungjin Baek, Sookyeong Han, Gun Min Kim, Joohyuk Sohn, Yumie Rhee, Namki Hong, Min Hwan Kim","doi":"10.1002/jcsm.13666","DOIUrl":"https://doi.org/10.1002/jcsm.13666","url":null,"abstract":"Recent evidence indicates that a dysregulated host metabolism influences treatment outcomes in patients with breast cancer. We investigated the association of computed tomography (CT)-derived body composition indices with therapeutic responses in patients with hormone receptor-positive, HER2-negative advanced breast cancer (ABC) on endocrine plus CDK4/6 inhibitor (CDK4/6i) treatment.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"49 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Mass Index Decline as a Predictor of Lung Function Reduction in the General Population","authors":"Joon Young Choi, Chin Kook Rhee, Sang Hyuk Kim, Yong Suk Jo","doi":"10.1002/jcsm.13663","DOIUrl":"https://doi.org/10.1002/jcsm.13663","url":null,"abstract":"This study explores the link between muscle mass decline and lung function deterioration, which can worsen respiratory health by reducing exercise capacity and quality of life. The relationship between muscle mass index (MMI) changes and lung function in the general population remains unclear, especially as muscle mass fluctuates with aging. We aimed to clarify this dynamic relationship by examining how changes in muscle mass impact pulmonary function and the development of respiratory symptoms.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"59 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan","authors":"Shih-Tsung Huang, Rei Otsuka, Yukiko Nishita, Lin-Chieh Meng, Fei-Yuan Hsiao, Hiroshi Shimokata, Liang-Kung Chen, Hidenori Arai","doi":"10.1002/jcsm.13660","DOIUrl":"https://doi.org/10.1002/jcsm.13660","url":null,"abstract":"Inconsistent results have been reported concerning the association between statin administration and muscle health, specifically its potential to increase the risk of sarcopenia. Given the widespread long-term use of statins among the elderly population, the exploration of this association remains a crucial yet insufficiently examined matter. This study aimed to assess the association between the prolonged administration of statins and the risk of sarcopenia, diminished muscle strength, reduced skeletal muscle mass and impaired physical performance.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"22 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers","authors":"Frank Misselwitz, Dennis Henderson, Somasekhara R. Menakuru, Elaine Morten, Chris Roe, Gareth Whitaker, Stefan Wohlfeil, John McDermott","doi":"10.1002/jcsm.13651","DOIUrl":"https://doi.org/10.1002/jcsm.13651","url":null,"abstract":"<i>S</i>-pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β-blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5-hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that <i>S</i>-pindolol can reverse weight loss and improve fat-free mass in patients with cancer-related weight loss. A comparative phase I bioavailability study of <i>S</i>-pindolol and racemic pindolol was performed to support the development of <i>S</i>-pindolol in cancer cachexia.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"5 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142810077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}