JCSM rapid communications最新文献

{"title":"Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans","authors":"Alyssa Marie M. Castillo,&nbsp;Trang T. Vu,&nbsp;Sophia G. Liva,&nbsp;Min Chen,&nbsp;Zhiliang Xie,&nbsp;Justin Thomas,&nbsp;Bryan Remaily,&nbsp;Yizhen Guo,&nbsp;Uma L. Subrayan,&nbsp;Travis Costa,&nbsp;Timothy H. Helms,&nbsp;Donald J. Irby,&nbsp;Kyeongmin Kim,&nbsp;Dwight H. Owen,&nbsp;Samuel K. Kulp,&nbsp;Thomas A. Mace,&nbsp;Mitch A. Phelps,&nbsp;Christopher C. Coss","doi":"10.1002/rco2.32","DOIUrl":"10.1002/rco2.32","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Monoclonal antibody (mAb) immune checkpoint inhibitor (ICI) therapies have dramatically impacted oncology this past decade. However, only about one-third of patients respond to treatment, and biomarkers to predict responders are lacking. Recent ICI clinical pharmacology data demonstrate high baseline drug clearance (CL₀) significantly associates with shorter overall survival, independent of ICI exposure, in patients receiving ICI mAb therapies. This suggests CL₀ may predict outcomes from ICI therapy, and cachectic signalling may link elevated CL₀ and poor response. Our aim was to determine if mouse models of cancer cachexia will be useful for studying these phenomena and their underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated pembrolizumab CL in the C26 and Lewis lung carcinoma mouse models of cancer cachexia. A single treatment of vehicle or pembrolizumab, at a dose of 2 or 10 mg/kg, was administered intravenously by tail vein injection. Pembrolizumab was quantified by an ELISA in serial plasma samples, and FcRn gene (<i>Fcgrt</i>) expression was assessed in liver using real-time quantitative reverse transcription PCR. Non-compartmental and mixed-effects pharmacokinetics analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed higher pembrolizumab CL₀ and decreased <i>Fcgrt</i> expression in whole liver tissue from tumour-bearing vs. tumour-free mice. In multivariate analysis, presence of tumour, total murine IgG, muscle weight and <i>Fcgrt</i> expression were significant covariates on CL, and total murine IgG was a significant covariate on V1 and Q.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data demonstrate increases in catabolic clearance of monoclonal antibodies observed in humans can be replicated in cachectic mice, in which <i>Fcgrt</i> expression is also reduced. Notably, FcRn activity is essential for proper antigen presentation and antitumour immunity, which may permit the study of cachexia's impact on FcRn-mediated clearance and efficacy of ICI therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 2","pages":"232-244"},"PeriodicalIF":0.0,"publicationDate":"2021-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39411380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle-specific over-expression of the nuclear sirtuin SIRT6 blocks cancer-associated cachexia by regulating multiple targets.","authors":"Sadhana A Samant, Vinodkumar B Pillai, Mahesh P Gupta","doi":"10.1002/rco2.27","DOIUrl":"10.1002/rco2.27","url":null,"abstract":"<p><strong>Background: </strong>During cancer cachexia, cytokines released from tumour cells can alter body's metabolism, which can lead to onset of this disease process. Biological basis of cachexia is multifactorial; hence, it is important to identify and modulate multiple targets to curtail the process of cachexia. Previously, we reported that the nuclear sirtuin, SIRT6, blocks expression of myostatin, a negative regulator of muscle growth, through modulation of the NF-κB signalling. This study was undertaken to test whether muscle-specific over-expression of SIRT6 can block the cancer-associated muscle wasting <i>in vivo</i> and to identify additional relevant targets of SIRT6, which can explain its ability to maintain muscle health.</p><p><strong>Methods: </strong>We generated a skeletal muscle-specific SIRT6 over-expressing transgenic mouse line (Sk.T6Tg) expressing SIRT6 at a moderate (two-fold to four-fold) level, compared with its control littermates. To generate a cancer-cachexia model, B16F10 mouse melanoma cells were injected subcutaneously in the flanks of mice. Gastrocnemius muscle tissues from non-tumour and tumour controls and Sk.T6Tg mice (<i>n</i> = 5-20) were analysed by histology, immunoblotting, and RT-qPCR. Plasma samples of mice were evaluated using cytokine arrays and ELISA in both non-tumour and tumour conditions.</p><p><strong>Results: </strong>Our results demonstrate dual benefits of muscle-specific moderate over-expression of SIRT6 in a mouse model of cancer-cachexia. In tumour-bearing mice, SIRT6 over-expression preserved muscle weight (<i>P</i> < 0.001) and fibre size (<i>P</i> < 0.005) as well as suppressed tumour growth (<i>P</i> < 0.05). SIRT6 over-expression significantly reduced myostatin expression and plasma free fatty acids levels but maintained plasma insulin levels in tumour-bearing mice. These positive effects of SIRT6 were associated with downregulation of the circulatory chemokine, CXCL10, and the myokine, WNT4. SIRT6 also upregulated expression of GLUT4, the major glucose transporter in the skeletal muscle. These results for the first time demonstrate that SIRT6 regulates multiple targets to limit tumour growth and cancer-associated muscle atrophy.</p><p><strong>Conclusion: </strong>Given the multifactorial nature of cachexia, SIRT6, which concurrently controls multiple pathways, can be a valuable therapeutic target to overcome this debilitating syndrome.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"40-56"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39141426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-induced Cardiac Atrophy Adversely Affects Myocardial Redox State and Mitochondrial Oxidative Characteristics.","authors":"David E Lee,&nbsp;Jacob L Brown,&nbsp;Megan E Rosa-Caldwell,&nbsp;Richard A Perry,&nbsp;Lemuel A Brown,&nbsp;Wesley S Haynie,&nbsp;Tyrone A Washington,&nbsp;Michael P Wiggs,&nbsp;Narasimhan Rajaram,&nbsp;Nicholas P Greene","doi":"10.1002/rco2.18","DOIUrl":"https://doi.org/10.1002/rco2.18","url":null,"abstract":"<p><p>Cachexia presents in 80% of advanced cancer patients; however, cardiac atrophy in cachectic patients receives little attention. This cardiomyopathy contributes to increased occurrence of adverse cardiac events compared to age-matched population norms. Research on cardiac atrophy has focused on remodeling; however, alterations in metabolic properties may be a primary contributor.</p><p><strong>Purpose: </strong>Determine how cancer-induced cardiac atrophy alters mitochondrial turnover, mitochondrial mRNA translation machinery and <i>in-vitro</i> oxidative characteristics.</p><p><strong>Methods: </strong>Lewis lung carcinoma (LLC) tumors were implanted in C57BL6/J mice and grown for 28days to induce cardiac atrophy. Endogenous metabolic species, and markers of mitochondrial function were assessed. H9c2 cardiomyocytes were cultured in LLC-conditioned media with(out) the antioxidant MitoTempo. Cells were analyzed for ROS, oxidative capacity, and hypoxic resistance.</p><p><strong>Results: </strong>LLC heart weights were ~10% lower than controls. LLC hearts demonstrated ~15% lower optical redox ratio (FAD/FAD+NADH) compared to PBS controls. When compared to PBS, LLC hearts showed ~50% greater COX-IV and VDAC, attributed to ~50% lower mitophagy markers. mt-mRNA translation machinery was elevated similarly to markers of mitochondrial content. mitochondrial DNA-encoded Cytb was ~30% lower in LLC hearts. ROS scavengers GPx-3 and GPx-7 were ~50% lower in LLC hearts. Treatment of cardiomyocytes with LLC-conditioned media resulted in higher ROS (25%), lower oxygen consumption rates (10% at basal, 75% at maximal), and greater susceptibility to hypoxia (~25%) -- which was reversed by MitoTempo.</p><p><strong>Conclusion: </strong>These results substantiate metabolic cardiotoxic effects attributable to tumor-associated factors and provide insight into interactions between mitochondrial mRNA translation, ROS mitigation, oxidative capacity and hypoxia resistance.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"3-15"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25471375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-associated skeletal muscle defects in HER2/Neu transgenic mammary tumor model.","authors":"Ruizhong Wang,&nbsp;Brijesh Kumar,&nbsp;Poornima Bhat-Nakshatri,&nbsp;Mayuri S Prasad,&nbsp;Max H Jacobsen,&nbsp;Gabriela Ovalle,&nbsp;Calli Maguire,&nbsp;George Sandusky,&nbsp;Trupti Trivedi,&nbsp;Khalid S Mohammad,&nbsp;Theresa Guise,&nbsp;Narsimha R Penthala,&nbsp;Peter A Crooks,&nbsp;Jianguo Liu,&nbsp;Teresa Zimmers,&nbsp;Harikrishna Nakshatri","doi":"10.1002/rco2.23","DOIUrl":"https://doi.org/10.1002/rco2.23","url":null,"abstract":"<p><strong>Background: </strong>Loss of skeletal muscle volume and resulting in functional limitations are poor prognostic markers in breast cancer patients. Several molecular defects in skeletal muscle including reduced MyoD levels and increased protein turn over due to enhanced proteosomal activity have been suggested as causes of skeletal muscle loss in cancer patients. However, it is unknown whether molecular defects in skeletal muscle are dependent on tumor etiology.</p><p><strong>Methods: </strong>We characterized functional and molecular defects of skeletal muscle in MMTV-Neu (Neu+) mice (n= 6-12), an animal model that represents HER2+ human breast cancer, and compared the results with well-characterized luminal B breast cancer model MMTV-PyMT (PyMT+). Functional studies such as grip strength, rotarod performance, and ex vivo muscle contraction were performed to measure the effects of cancer on skeletal muscle. Expression of muscle-enriched genes and microRNAs as well as circulating cytokines/chemokines were measured. Since NF-κB pathway plays a significant role in skeletal muscle defects, the ability of NF-κB inhibitor dimethylaminoparthenolide (DMAPT) to reverse skeletal muscle defects was examined.</p><p><strong>Results: </strong>Neu+ mice showed skeletal muscle defects similar to accelerated aging. Compared to age and sex-matched wild type mice, Neu+ tumor-bearing mice had lower grip strength (202±6.9 vs. 179±6.8 g grip force, p=0.0069) and impaired rotarod performance (108±12.1 vs. 30±3.9 seconds, P<0.0001), which was consistent with reduced muscle contractibility (p<0.0001). Skeletal muscle of Neu+ mice (n=6) contained lower levels of CD82+ (16.2±2.9 vs 9.0±1.6) and CD54+ (3.8±0.5 vs 2.4±0.4) muscle stem and progenitor cells (p<0.05), suggesting impaired capacity of muscle regeneration, which was accompanied by decreased MyoD, p53 and miR-486 expression in muscles (p<0.05). Unlike PyMT+ mice, which showed skeletal muscle mitochondrial defects including reduced mitochondria levels and Pgc1β, Neu+ mice displayed accelerated aging-associated changes including muscle fiber shrinkage and increased extracellular matrix deposition. Circulating \"aging factor\" and cachexia and fibromyalgia-associated chemokine Ccl11 was elevated in Neu+ mice (1439.56±514 vs. 1950±345 pg/ml, p<0.05). Treatment of Neu+ mice with DMAPT significantly restored grip strength (205±6 g force), rotarod performance (74±8.5 seconds), reversed molecular alterations associated with skeletal muscle aging, reduced circulating Ccl11 (1083.26 ±478 pg/ml), and improved animal survival.</p><p><strong>Conclusions: </strong>These results suggest that breast cancer subtype has a specific impact on the type of molecular and structure changes in skeletal muscle, which needs to be taken into consideration while designing therapies to reduce breast cancer-induced skeletal muscle loss and functional limitations.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"24-39"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25598818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced adenosine diphosphate sensitivity in skeletal muscle mitochondria increases reactive oxygen species production in mouse models of aging and oxidative stress but not denervation.","authors":"Gavin Pharaoh, Jacob Brown, Rojina Ranjit, Zoltan Ungvari, Holly Van Remmen","doi":"10.1002/rco2.29","DOIUrl":"10.1002/rco2.29","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial bioenergetics are sensitive to adenosine diphosphate (ADP) concentration. Reactive oxygen species (ROS) production and respiration [oxygen consumption rate (OCR)] are altered at physiological ADP concentrations (i.e. ADP insensitivity) in aged human muscle. Here, we investigate ADP sensitivity in mouse muscle mitochondria.</p><p><strong>Methods: </strong>We measured OCR and ROS production in permeabilized gastrocnemius fibres using an ADP titration protocol and the Oroboros O2k respirometer and fluorometer. We measured changes in ADP sensitivity in muscle from mice at different ages, after sciatic nerve transection (denervation), and in response to increased oxidative stress (<i>Sod1</i> ^-/- mice). Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the <i>Sod1</i> ^-/- mouse model.</p><p><strong>Results: </strong>Reduced ADP sensitivity is associated with increases in mitochondrial ROS production in aged (62%) and <i>Sod1</i> ^-/- (33%) mice. The maximal capacity to produce ROS does not increase with age, and there is no effect of age on ADP sensitivity for OCR in mouse gastrocnemii. Denervation does not induce ADP insensitivity for either ROS generation or OCR. Treatment of <i>Sod1</i> ^-/- mice with SS-31 increases ADP sensitivity for both OCR and ROS, decreases maximal ROS production (^~40%), and improves resistance to muscle fatigue.</p><p><strong>Conclusions: </strong>Adenosine diphosphate sensitivity for ROS production decreases in aged mouse gastrocnemius muscle fibres, although aged mice do not exhibit a difference in OCR. Denervation does not induce ADP insensitivity; however, insensitivity to ADP is induced in a model of oxidative stress. ADP insensitivity could contribute to muscle fatigue, and SS-31 may be the first drug capable of targeting this aging phenotype.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"75-89"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33483970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyamine pathway is associated with muscle anabolic effects by androgen receptor ligand","authors":"M. Kanou, Katsuyuki Nakamura, Kyohei Horie, H. Sakai, Yuta Yanagihara, Iori Sakakibara, K. Yamana, Yuuki Imai","doi":"10.1002/rco2.28","DOIUrl":"https://doi.org/10.1002/rco2.28","url":null,"abstract":"Muscle wasting is a common condition concomitant with aging. Androgens significantly increase skeletal muscle mass, but the role of the androgen receptor (AR) in skeletal muscle is not well established. TEI‐SARM2, a novel selective androgen receptor modulator (SARM), was developed as a pharmaceutical candidate for the treatment of muscle wasting diseases.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"57 - 74"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.28","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47449637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of sarcopenia in middle‐aged and older patients in post‐acute inpatient rehabilitation: a cross‐sectional study","authors":"I. Churilov, L. Churilov, K. Brock, Navina Curtain, D. Murphy, Kavitha Muthukrishnan, R. MacIsaac, E. Ekinci","doi":"10.1002/rco2.25","DOIUrl":"https://doi.org/10.1002/rco2.25","url":null,"abstract":"Despite the recommendation of European Working Group on Sarcopenia in Older People 2 (EWGSOP2) consensus statement not to exclude patients younger than 65 years, the prevalence of sarcopenia has not been investigated in younger post‐acute inpatient rehabilitation population. The objectives of this study were to: i) estimate the prevalence of sarcopenia in post‐acute inpatient rehabilitation population; ii) compare the prevalence of sarcopenia in patients above and below 65 years.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"4 1","pages":"16 - 23"},"PeriodicalIF":0.0,"publicationDate":"2020-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49065803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Janus kinase inhibitors suppress cancer cachexia-associated anorexia and adipose wasting in mice","authors":"Gurpreet K. Arora,&nbsp;Arun Gupta,&nbsp;Tong Guo,&nbsp;Aakash Y. Gandhi,&nbsp;Aaron Laine,&nbsp;Dorothy L. Williams,&nbsp;Chul Ahn,&nbsp;Puneeth Iyengar,&nbsp;Rodney E. Infante","doi":"10.1002/rco2.24","DOIUrl":"https://doi.org/10.1002/rco2.24","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cachexia, a syndrome of muscle atrophy, adipose loss, and anorexia, is associated with reduced survival in cancer patients. The colon adenocarcinoma C26c20 cell line secretes the cytokine leukaemia inhibitory factor (LIF), which induces cachexia. We characterized how LIF promotes cachexia-associated weight loss and anorexia in mice through Janus kinase (JAK)-dependent changes in adipose and hypothalamic tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cachexia was induced <i>in vivo</i> with the heterotopic allotransplanted administration of C26c20 colon adenocarcinoma cells or the intraperitoneal administration of recombinant LIF in the absence or presence of JAK inhibitors. Blood, adipose, and hypothalamic tissues were collected and processed for cytokine/adipokine enzyme-linked immunosorbent assays, immunoblot analysis, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Cachexia-associated lipolysis was induced <i>in vitro</i> by stimulating differentiated adipocytes with recombinant LIF or interleukin (IL)-6 in the absence or presence of lipase or JAK inhibitors. These adipocytes were processed for glycerol release into the media, immunoblot analysis, and RT-PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tumour-secreted LIF induced changes in adipose tissue expression and serum levels of IL-6 and leptin in a JAK-dependent manner influencing cachexia-associated adipose wasting and anorexia. We identified two JAK inhibitors that block IL-6 family-mediated adipocyte lipolysis and IL-6 induction using an <i>in vitro</i> cachexia lipolysis assay. JAK inhibitors administered to the <i>in vivo</i> C26c20 cancer cachexia mouse models led to (i) a decrease in signal transducer and activator of transcription 3 phosphorylation in hypothalamic and adipose tissues, (ii) a reverse in the cachexia serum cytokine/adipokine signature, (iii) a delay in cancer cachexia-associated anorexia and adipose loss, and (iv) an improvement in overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>JAK inhibitors suppress LIF-associated adipose loss and anorexia in both <i>in vitro</i> and <i>in vivo</i> models of cancer cachexia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"3 2","pages":"115-128"},"PeriodicalIF":0.0,"publicationDate":"2020-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71978550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computed tomography, not bioelectrical impedance analysis, is the proper method for evaluating changes in skeletal muscle mass in liver disease","authors":"Masatsugu Ohara,&nbsp;Goki Suda,&nbsp;Megumi Kimura,&nbsp;Osamu Maehara,&nbsp;Tomoe Shimazaki,&nbsp;Taku Shigesawa,&nbsp;Kazuharu Suzuki,&nbsp;Akihisa Nakamura,&nbsp;Naoki Kawagishi,&nbsp;Masato Nakai,&nbsp;Takuya Sho,&nbsp;Mitsuteru Natsuizaka,&nbsp;Kenichi Morikawa,&nbsp;Koji Ogawa,&nbsp;Naoya Sakamoto","doi":"10.1002/rco2.20","DOIUrl":"10.1002/rco2.20","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is associated with poor prognosis in patients with chronic liver disease (CLD). As rapid skeletal muscle wasting predicts worse prognosis and a novel therapy for sarcopenia needs to be evaluated for validation, accurate evaluation methods for relative changes in muscle mass are crucial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We screened CLD patients who had skeletal muscle mass evaluation between June 2015 and December 2017. Patients were included if they had adequate information, were followed for &gt;6 months, and had skeletal muscle mass evaluation by both bioelectrical impedance analysis (BIA) and computed tomography (CT) imaging at baseline and the second evaluation point. We compared BIA and CT imaging in terms of their ability to quantify skeletal muscle mass and identify relative changes in muscle mass in CLD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the screened 447 CLD patients, 110 were included in this study, and 71 (64.5%) were men. The median age was 68 (range 21 to 90) years. In total, 83 (75.5%) and 32 (29.1%) patients had liver cirrhosis and hepatocellular carcinoma, respectively. Of them, 50 (45.5%) patients were liver cirrhosis patients without hepatocellular carcinoma through the observation period. Skeletal muscle mass index (SMI) by BIA, psoas muscle mass index (PMI), and SMI based on CT imaging were significantly correlated at baseline [SMI by simple CT method and SMI by BIA (<i>r</i> = 0.61, <i>P</i> &lt; 0.01), SMI by BIA and PMI (<i>r</i> = 0.65, <i>P</i> &lt; 0.01), and SMI by simple CT method and PMI (<i>r</i> = 0.82, <i>P</i> &lt; 0.01), respectively] and second evaluation point [SMI by simple CT method and SMI by BIA (<i>r</i> = 0.51, <i>P</i> &lt; 0.01), SMI by BIA and PMI (<i>r</i> = 0.58, <i>P</i> &lt; 0.01), and SMI by simple CT method and PMI (<i>r</i> = 0.92, <i>P</i> &lt; 0.01), respectively]. Similar to previous reports, based on the PMI and SMI by simple CT method, patients with more severe liver dysfunction experienced more rapid skeletal muscle mass loss (ΔSimple method/years and ΔPMI/years in patients with Child‑Pugh Classes A, B, and C: Child‑Pugh A, −3.34%; B, −11.77%; C, −18.78%; and Child‑Pugh A, −0.78%; B, −6.33%; C, −7.71%, respectively). Completely opposite results were obtained based on SMI by BIA (Child‑Pugh A, −0.70%; B, 1.42%; C, 12.48%). A subgroup analysis revealed that in patients with fluid retention and diuretic administration, SMI by BIA increased with time (<i>P</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"3 2","pages":"103-114"},"PeriodicalIF":0.0,"publicationDate":"2020-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47167239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of cancer-related weight loss and sarcopenia in the UK and Ireland: incidence, prevalence, and clinical impact","authors":"Erin S. Sullivan,&nbsp;Louise E. Daly,&nbsp;Derek G. Power,&nbsp;Aoife M. Ryan","doi":"10.1002/rco2.19","DOIUrl":"10.1002/rco2.19","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Weight loss (WL) and sarcopenia are associated with negative oncological outcomes including poor treatment tolerance, decreased quality of life, and reduced survival. The number of patients affected by sarcopenia and WL in Ireland and the UK is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was undertaken to determine median rate of WL &gt; 5% and computed tomography-diagnosed sarcopenia in oncology populations. Gaps in the literature were supplemented using local data, collected as part of a 5 year prospective study. Rates of WL and sarcopenia in the population were extrapolated from these data based on incidence and prevalence of each cancer as per national cancer registries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We estimated that across Ireland and the UK, 128 892 cancer patients (34%) are affected by WL &gt; 5% annually (121 641 UK; 7251 Ireland) and there are 133 707 annual cases of sarcopenia in cancer patients (35%) (126 265 UK; 7442 Ireland). Furthermore, we estimate that there are 716 124 and 771 589 cancer survivors with history of WL &gt; 5% or sarcopenia, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Large numbers of patients are affected by cancer-related malnutrition. Given the impact of malnutrition on oncological outcomes and long-term frailty, there is an urgent need to improve access to cancer nutrition care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"3 2","pages":"91-102"},"PeriodicalIF":0.0,"publicationDate":"2020-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48573176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}