JCSM rapid communications最新文献

{"title":"Exercise intervention during chemotherapy for pancreatic cancer: Changes in body composition and function","authors":"Kathryn H. Schmitz,&nbsp;Robert D. Boutin,&nbsp;James P. Yoon,&nbsp;Melanie Potiaumpai,&nbsp;Leon Lenchik,&nbsp;Carissa M. White,&nbsp;Victor Chang","doi":"10.1002/rco2.74","DOIUrl":"10.1002/rco2.74","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with pancreatic cancer often lose weight during chemotherapy with associated changes in body composition. The goal of the present analysis was to describe changes in body composition in pancreatic cancer patients on an exercise regimen. The long-term goal is to determine whether an exercise intervention may attenuate changes in body composition and function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-two pancreatic cancer patients of all stages who were to receive chemotherapy were recruited into a pre-post exercise intervention study. A standard exercise prescription was individualized to include aerobic, resistance, stretch, and balance exercises. Pre- and post-intervention computed tomography-derived measures of body composition [skeletal muscle index (SMI), skeletal muscle density, visceral fat area, and subcutaneous fat area] and physical function measures (grip strength, timed up and go, 30-s chair stand, and tandem balance stand) were evaluated using paired <i>t</i>-tests, χ² tests, and Pearson correlation coefficients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The subjects were, on average, 62 years of age, 55% were female, 95% non-Hispanic White, and 45% were Stage IV. Body composition changes included a median 4.6% decrease in SMI (<i>P</i> = 0.04), 7.91% increase in skeletal muscle density (<i>P</i> = 0.05), 25.07% decrease in visceral fat area (<i>P</i> = 0.0001), and 22.08% decrease in subcutaneous fat area (<i>P</i> = 0.001). Adherence to aerobic and strength exercise was 65% and 57%, respectively. Some physical function measures improved, though not significantly: chair stands increased from a mean of 11.5 to 13.0 (<i>P</i> = 0.59) and timed up and go improved from a mean of 11.7 to 10.3 (<i>P</i> = 0.26). Change in right hand grip strength was marginally positively associated with changes in SMI (<i>r</i> = 0.53, <i>P</i> = 0.06). Improvements in skeletal muscle density were seen in 63% of patients, including Stage IV patients but did not correlate with change in function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Exercise is feasible during neoadjuvant chemotherapy for pancreatic cancer patients of all stages and may assist with maintaining physical function and improving body composition. Further research is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"33-41"},"PeriodicalIF":0.0,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.74","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41846287","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":"A Toll-like receptor-4/NLRP3 inflammasome pathway promotes inflammation in skeletal muscle of chronic kidney disease patients","authors":"Daniela Verzola,&nbsp;Pasquale Esposito,&nbsp;Samantha Milanesi,&nbsp;Michela Saio,&nbsp;Daniela Picciotto,&nbsp;Marco Frascio,&nbsp;Alessandro Laudon,&nbsp;Giacomo Garibotto,&nbsp;Giuliano Brunori,&nbsp;Francesca Viazzi","doi":"10.1002/rco2.75","DOIUrl":"10.1002/rco2.75","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An emerging hypothesis is that the activation of innate immunity in the muscle of patients with chronic kidney disease (CKD) is implicated in the development and progression of wasting and cachexia. We previously observed that Toll-like receptor-4 (TLR4) and its downward NF-κB-dependent pro-inflammatory pathways are activated in CKD muscle. It is however unknown if TLR4 can activate the TLR4/NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway, which is implicated in cardiovascular disease and frailty, clinical settings that are commonly observed in CKD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a case–control cohort study, we hypothesized that a TLR4/NLRP3 inflammasome pathway is activated in skeletal muscle in uraemia. First, we studied the regulation TLR4/NLRP3/caspase-1 in skeletal muscle biopsies (20M/11F) obtained from 31 non-diabetic CKD5 patients (eGFR 8 ± 1 mL/min 1.73 m²) scheduled for peritoneal dialysis catheter insertion and 15 controls (10M/5F, eGFR 99 ± 6 mL/min 1.73 m²). Second, the effects of uraemic serum on the TLR4/NLRP3 inflammasome pathway were studied in C2C12 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the muscle of CKD subjects, NLRP3 mRNA as well as its protein were overexpressed (by ~16-fold, respectively, <i>P</i> &lt; 0.05 both vs. controls). Both IL-1β and IL-18 mRNA expressions were also up-regulated (~11.8–3.2-fold, respectively, <i>P</i> &lt; 0.05). Also, cleaved caspase-1 was overexpressed in CKD muscle samples (<i>P</i> &lt; 0.001 vs. controls). Both muscle NLRP3 mRNA (<i>n</i> = 22, <i>r</i> = −0.606, <i>P</i> &lt; 0.01) and logIL-1 β protein (<i>n</i> = 26, <i>r</i> = −0.460, <i>P</i> &lt; 0.02) were inversely associated with residual renal function, which suggests that the inflammasome is progressively activated in skeletal muscle of CKD patients as the residual renal function deteriorates. In addition, we observed that in C2C12 myotubes, uraemic serum up-regulates NLRP3 mRNA (~11-fold increase, <i>P</i> &lt; 0.05), cleaved caspase-1 (by ~5-fold, <i>P</i> &lt; 0.05), Il-1β mRNA (~3-fold increase, <i>P</i> &lt; 0.05) and oxidative stress markers respect to normal serum. These effects were prevented by TAK-242, a selective TLR4 inhibitor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, our data demonstrate the activation of TLR4/NLRP3/caspase-1 inflammasome and its downward inflammatory cascade in the muscle of subjects with advanced-stage CKD and suggest targeting TLR4/NLRP3 inflammasome a","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"50-61"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.75","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44729050","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":"Body mass index and natriuretic peptides trends before and after left ventricular assist device","authors":"Jessica Schultz,&nbsp;Amanda R. Vest,&nbsp;Maria Masotti,&nbsp;Austin Hoeg,&nbsp;Levi Teigen,&nbsp;Ranjit John,&nbsp;Andrew Shaffer,&nbsp;Tamas Alexy,&nbsp;Cindy Martin,&nbsp;Rebecca Cogswell","doi":"10.1002/rco2.76","DOIUrl":"10.1002/rco2.76","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is unknown to what degree of sarcopenia related to heart failure (HF) is reversible with resolution of the HF syndrome. We evaluated whether (1) weight loss prior to left ventricular assist device (LVAD) is associated with pre-operative sarcopenia as quantified on pre-operative chest CTs and (2) determine the relationship between weight recovery (increase) after LVAD implantation and reduction of NT-proBNP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a large single-centre cohort (<i>n</i> = 502), CT measures of sarcopenia (pectoralis muscle mass indexed to body surface area and tissue attenuation) were correlated with pre-LVAD BMI trend (<i>n</i> = 190). BMI and NT-proBNP trends before and after LVAD implantation were evaluated (<i>n</i> = 403). Linear effects modelling was performed to test the association between NT-proBNP and BMI trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A downtrending BMI prior to LVAD was associated with pectoralis muscle tissue attenuation (<i>P</i> &lt; 0.05). BMI declined prior to LVAD, declined further early post-implant, and then increased between 100 and 300 days post-implant (average per cent change in BMI in Year 1, 7.6%, 95% CI: 6.3–8.8%). NT-proBNP decreased during the first 100 post LVAD days (−5.4%, 95% CI: −6.6 to −4.2%). Post-LVAD NT-proBNP and BMI trends were significantly associated, with a decrease of 1 unit log NT-proBNP associated with an increase in BMI of 0.81 kg/m² (CI: 0.53–1.09, <i>P</i> &lt; .001). The rise in post-LVAD BMI occurred after the reduction in NT-proBNP levels. Patients who failed to gain weight post-LVAD had the highest 6-month post-LVAD natriuretic peptides (lowest per cent BMI gain tertile NT-proBNP: 2208 vs. highest 1635 pg/mL, <i>P</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Weight recovery during LVAD support occurs after the reduction in natriuretic peptide levels. Failure to gain weight during LVAD support was associated with persistently elevated natriuretic peptide levels. These data collectively suggest that recovery of body mass may be dependent upon recovery of the HF syndrome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"42-49"},"PeriodicalIF":0.0,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.76","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41649925","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":"Different reversibility of skeletal muscle mass and strength in elderly Japanese women after the first wave of COVID-19","authors":"Bo-Kyung Son,&nbsp;Toshiyuki Imoto,&nbsp;Tomohiro Inoue,&nbsp;Takatoshi Nishimura,&nbsp;Weida Lyu,&nbsp;Tomoki Tanaka,&nbsp;Katsuya Iijima","doi":"10.1002/rco2.73","DOIUrl":"10.1002/rco2.73","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Restrictions on outdoor movements due to the coronavirus disease (COVID-19) pandemic have led to a decreased physical activity; this can lead to sarcopenia and frailty in older adults. Our recent study has demonstrated a significant decrease in the trunk muscle mass immediately after the pandemic's first wave (April–May 2020) among Japanese community-dwelling older women. In the present study, we further examined whether muscle mass recovery or deterioration occurs after 1 year of the pandemic's first wave by comparing physical measurements among the following assessment periods: before the first wave, immediately after the first wave, and at 1-year follow-up thereafter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 77 women (78.0 ± 5.7 years) who underwent physical measurements for muscle mass, grip strength, one-leg stand-up ability (3 s), and oral motor skills and answered questionnaires on sociality (social network, participation, and support) in the three assessment periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The frequency of going out and the subjective vitality were significantly decreased immediately after the first wave; these recovered at the 1-year follow-up (<i>P</i> &lt; 0.001). When comparing muscular measures, the trunk muscle mass index preferentially decreased immediately after the first wave but recovered significantly at the 1-year follow-up (<i>P</i> &lt; 0.001). Conversely, the appendicular skeletal muscle mass index (ASMI) and grip strength continued to decrease until the 1-year follow-up (<i>P</i> &lt; 0.001 and <i>P</i> = 0.03, respectively). The ability to perform a one-leg stand-up for 3 s and the oral motor skills did not change significantly across the assessment periods. The prevalence of pre-sarcopenia and sarcopenia tended to increase during these periods (<i>P</i> = 0.068). The reduction and subsequent recovery patterns for sociality were similar to those observed for the trunk muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrated differences in the reversibility of skeletal muscle mass and strength at 1 year after the first wave of the COVID-19 pandemic: the trunk muscle mass declined acutely and recovered rapidly, whereas the ASMI and grip strength declined continuously. These differences in the skeletal muscle recovery and deterioration might help formulate short-term or long-term strategies for COVID-19-related sarcopenia prevention in community-dwelling older adults.</p>\u0000 </section>\u0000 ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"26-32"},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.73","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49229886","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":"Patient-derived pancreatic tumour organoid implantation establishes novel pre-cachexia mouse models","authors":"Merel R. Aberle,&nbsp;Rianne D.W. Vaes,&nbsp;Wouter R.P.H. van de Worp,&nbsp;Ludwig J. Dubois,&nbsp;Natasja G. Lieuwes,&nbsp;Rianne Biemans,&nbsp;Ramon C.J. Langen,&nbsp;Frederik-Jan van Schooten,&nbsp;Ronald M. van Dam,&nbsp;Steven W.M. Olde Damink,&nbsp;Sander S. Rensen","doi":"10.1002/rco2.71","DOIUrl":"10.1002/rco2.71","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The poor survival of pancreatic cancer patients is largely attributable to cachexia, a syndrome of severe weight and muscle loss. To investigate the aetiology of cancer cachexia, preclinical models that closely recapitulate the human disease process are essential. Patient derived tumour organoids are promising novel cancer models, but their ability to induce cachexia in mice has not been investigated. We developed two pancreatic tumour organoid-based mouse models and demonstrate their potential for cancer cachexia research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two patients with pancreatic cancer, from whom tumour organoid cultures were previously established, were selected based on their cachexia phenotype. Patient 09 was characterized as cachectic according to the international consensus definition of cancer cachexia, whereas patient 12 was classified as non-cachectic. Organoid cultures PANCO-09b and PANCO-12a in basement membrane extract (BME) were injected subcutaneously into the flanks of 9-weeks old NMRI-<i>Foxn1</i>^<i>nu</i> mice (<i>n</i> = 8/group). A control group was injected with BME only (<i>n</i> = 4). Body weight was monitored every 2–3 days for 38 days. Hind limb muscle wet and dry weights were measured. Adipocyte size in inguinal white adipose tissue was measured using haematoxylin and eosin-stained sections. Expression of genes associated with cancer cachexia in muscle and liver tissue was analysed using qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Engraftment of tumour organoids was successful in 87.5% of PANCO-09b implanted mice and in 50% of PANCO-12a mice, with similar average tumour weights at endpoint (34.4 ± 25.1 mg vs. 32.8 ± 40.2 mg, respectively, <i>P</i> = 0.450). All groups initially gained weight, but PANCO-12a implanted mice progressively lost an average body weight of 1.7 ± 0.8 g from day 28 onwards. PANCO-12a-implanted mice gained significantly less weight from baseline than controls (0.7 ± 0.6 g, <i>P</i> = 0.027). Overall body weight gain of PANCO-09b mice was also lower but not significantly different from controls (2.0 ± 1.2 g vs. 2.9 ± 1.6 g, <i>P</i> = 0.961). Wet weights of hind leg muscles were negatively correlated with tumour weight but did not differ between groups. Adipocytes of PANCO-12a implanted mice were smaller compared to SHAM as well as PANCO09b mice (<i>P</i> &lt; 0.0001), indicative of white adipose tissue wasting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Implantation of human pancreatic tumour organoids into mice negati","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"4-17"},"PeriodicalIF":0.0,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.71","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48217491","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":"Risedronate use may blunt appendicular lean mass loss secondary to sleeve gastrectomy: results from a pilot randomized controlled trial","authors":"Laura E. Flores,&nbsp;Kristen M. Beavers,&nbsp;Daniel P. Beavers,&nbsp;Katelyn A. Greene,&nbsp;Diana A. Madrid,&nbsp;Ryan M. Miller,&nbsp;Jamy D. Ard,&nbsp;Laura D. Bilek,&nbsp;Ashley A. Weaver","doi":"10.1002/rco2.72","DOIUrl":"10.1002/rco2.72","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of 6 months of risedronate (vs. placebo) on change in dual-energy x-ray absorptiometry (DXA)- and computed tomography (CT)-derived lean mass metrics in the year following SG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four SG patients were randomized to 6 months of 150-mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and 6 months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% confidence intervals (CIs) were generated from a mixed model using contrast statements at 6 and 12 months, adjusted for baseline values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 24 participants enrolled [55.7 ± 6.7 years (mean ± SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7 ± 6.3 kg/m²], 21 returned for 6-month testing and 14 returned for 12-month testing. Six-month weight loss was −16.3 kg (−20.0, −12.5) and −20.9 kg (−23.7, −18.1) in the risedronate and placebo groups, respectively (<i>P</i> = 0.057). Primary analysis at 6 months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared with placebo [−1.2 kg (−2.3, −0.1) vs. −2.1 kg (−3.0, −1.2)]; <i>P</i> = 0.20. By 12 months, the risedronate group displayed no change in appendicular lean mass from baseline [−0.5 kg (−1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [−2.9 kg (−3.6, −2.1)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pilot data indicate that risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"18-25"},"PeriodicalIF":0.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583542","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":"Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer-induced cachexia.","authors":"Jeffery M Chakedis,&nbsp;Mary E Dillhoff,&nbsp;Carl R Schmidt,&nbsp;Priyani V Rajasekera,&nbsp;David C Evans,&nbsp;Terence M Williams,&nbsp;Denis C Guttridge,&nbsp;Erin E Talbert","doi":"10.1002/rco2.68","DOIUrl":"10.1002/rco2.68","url":null,"abstract":"<p><strong>Background: </strong>Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.</p><p><strong>Methods: </strong>Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia.</p><p><strong>Results: </strong>Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males.</p><p><strong>Conclusions: </strong>Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 2","pages":"254-265"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797184/pdf/nihms-1812924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10108764","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":"Risedronate or Exercise for Lean Mass Preservation During Menopause: Secondary Analysis of a Randomized Controlled Trial.","authors":"Laura E Flores, Kevin Kupzyk, Nancy Waltman, Kristen M Beavers, Laura Bilek","doi":"10.1002/rco2.59","DOIUrl":"10.1002/rco2.59","url":null,"abstract":"<p><strong>Background: </strong>The menopause transition is marked by hormonal shifts leading to body composition changes, such as fat mass gain and lean mass loss. Weight-bearing and resistance exercise can help maintain lean mass during the menopause transition; however, uptake is low. Pre-clinical research points to bisphosphonates as also being effective in preventing loss of lean mass. Thus, we sought to investigate whether bisphosphonate therapy can mitigate loss of lean mass and outperform weight-bearing exercise in the years immediately following menopause.</p><p><strong>Methods: </strong>Data come from the Heartland Osteoporosis Prevention Study (NCT02186600), where osteopenic, postmenopausal women were randomized to bisphosphonate (n=91), weight-bearing/resistance exercise (n=92), or control (n=93) conditions over a one-year period. Dual energy X-ray absorptiometry (DXA)-derived body composition measures (including total lean mass, total fat mass, lean mass index, and lean mass-to-fat mass ratio) were ascertained at baseline, six, and 12-months. Adherence to risedronate and weight-bearing exercise was defined as the percentage of dosages taken and exercise sessions attended. Intent-to-treat analysis using linear modeling was used to generate treatment effects on body composition. Secondary analysis utilized per-protocol analysis and included adjustment for weight change.</p><p><strong>Results: </strong>276 women (age: 54.5 years; 83.3% Caucasian; BMI: 25.7 kg/m²) were included in the analyses. 12-month adherence to the risedronate and exercise interventions was 89% and 64%, respectively. Group-by-time interactions were observed for lean mass, revealing exercise (0.43±1.49kg) and risedronate groups (0.31±1.68 kg) gained significantly more lean mass than control (-0.15±1.27 kg) over 12-months. However, after controlling for weight change in secondary analysis, the difference in lean mass change between control and risedronate became non-significant (<i>p=0.059</i>).</p><p><strong>Conclusions: </strong>Results suggest both 12 months of oral risedronate and 12 months of weight-bearing exercise may diminish lean mass loss experienced during the menopause transition as compared to control. The lean mass sparing effect for risedronate may be driven by overall weight change.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 2","pages":"154-161"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517955/pdf/nihms-1778461.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729676","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":"MRI thigh measurements predict whole‐body skeletal muscle mass in patients with type 2 diabetes: a comparison with DXA","authors":"E. Brown, A. Williams, O. Hakim, M. Wilton, J. Harrold, David Hughes, G. Kemp, J. Wilding, L. Goff, D. Cuthbertson","doi":"10.1002/rco2.70","DOIUrl":"https://doi.org/10.1002/rco2.70","url":null,"abstract":"Sarcopenia is an age‐related loss of skeletal muscle mass (SMM) and function, associated with falls, frailty, and functional decline. It is more prevalent and often accelerated in people with Type 2 diabetes (T2D), especially when co‐existing with obesity (sarcopenic obesity). Accurate whole‐body SMM measurement, feasible using dual‐energy X‐ray absorptiometry (DXA) or magnetic resonance imaging (MRI), has utility both in clinical practice and in epidemiological and mechanistic research, considering the dual mechanical and metabolic function of skeletal muscle. Compared with MRI, DXA may underestimate age‐related muscle mass by up to 30%, and so direct comparison of DXA/MRI‐derived SMM measurements may be invalid in patients with obesity and T2D, who have potentially even more pronounced sarcopenia/sarcopenic obesity. We aimed to validate single‐slice or multiple‐slice measures of SMM, using MRI, with whole‐body SMM measures derived from DXA scans of appendicular lean soft tissue, specifically in patients with obesity and T2D.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 1","pages":"149 - 153"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47873245","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":"Rescue of a peroxisome proliferator activated receptor gamma gene network in muscle after growth of human breast tumour xenografts","authors":"David A. Stanton, Hannah E. Wilson, Matthew G. Chapa, J. Link, Kristin Lupinacci, W. Geldenhuys, E. Pistilli","doi":"10.1002/rco2.69","DOIUrl":"https://doi.org/10.1002/rco2.69","url":null,"abstract":"Fatigue is common in patents with breast cancer (BC), and can occur in patients with early stage disease and in the absence of muscle wasting (i.e. cachexia). We have reported transcriptional and proteomic alterations in muscles from BC patients, which are associated with fatigue. Mice implanted with human BC xenografts recapitulate the muscle molecular composition changes seen in patients, coupled with a greater rate of contraction‐induced fatigue. Multiple bioinformatics platforms in both human and mouse muscles have identified peroxisome proliferator activated receptor gamma (PPARG) as central to this phenotype, with several PPARG target genes downregulated in muscle in response to tumour growth. The current study tested the hypothesis that the PPARG agonist pioglitazone (pio), a commonly prescribed diabetes drug, would rescue the transcriptional alterations observed in muscles of tumour‐bearing mice.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 1","pages":"239 - 253"},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43373166","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}