JCSM rapid communications最新文献

{"title":"Muscle atrophy in osteoarthritis: clinical features, pathological changes, underlying mechanisms, and exercise-based interventions","authors":"Tongyi Zhang,&nbsp;Bin Zhang,&nbsp;Jinhui Wu,&nbsp;Song Li,&nbsp;Yunquan Gong,&nbsp;Shunzheng Fang,&nbsp;Daibo Feng,&nbsp;Bo Huang,&nbsp;Jiqin Lian,&nbsp;Wei Xiang,&nbsp;Lin Chen,&nbsp;Zhenhong Ni","doi":"10.1002/rco2.99","DOIUrl":"https://doi.org/10.1002/rco2.99","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Osteoarthritis (OA) is a common degenerative disease with cartilage injury as the core pathological phenotype, which has become the leading cause of disability in the elderly. Skeletal muscle is an important organ to maintain the structure and motor function of joints, which is highly related to OA progress. Patients with OA typically exhibit abnormalities in the skeletal muscles surrounding the joints, such as reduced muscle mass and strength. We refer to this condition as OA-related muscle atrophy (hereafter referred to as OAMA). The mechanisms of OAMA are multifactorial and unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review, we summarized relevant research progress of OAMA (i) to review the changes in skeletal muscle of patients with OA, (ii) to review the underlying biological mechanisms of OAMA, (iii) to review the effects of skeletal muscle on OA, and (iv) to provide perspectives on current and potential strategies of OA clinical treatment based on skeletal muscle, especially exercise training.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>OAMA may lead to the destruction of joint stability and cartilage homeostasis and then promote the occurrence and development of OA. Clinical manifestations of OAMA are a decline in muscle mass and strength and an abnormal movement pattern. The underlying biological mechanisms of OAMA include chronic inflammation, oxidative stress, ion metabolism, glycolipid metabolism, and epigenetics. The effects of skeletal muscle on OA are skeletal muscle-mediated cartilage damage via biomechanics, muscle-derived secretions, and muscle-derived stem cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>More preclinical and clinical studies are imperative to study the mechanisms of OAMA and develop potential strategies. We hope that more studies can focus on the skeletal muscle during the OA process, which will be beneficial for delaying OA progression and improving the motor function of OA patients in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762348","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":"Effects of Pemafibrate on Serum Carnitine and Plasma Myostatin in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease","authors":"Ryohei Tanigawa,&nbsp;Atsushi Nakajima,&nbsp;Yuichiro Eguchi,&nbsp;Hirokazu Takahashi,&nbsp;Rohit Loomba,&nbsp;Hideki Suganami,&nbsp;Masaya Tanahashi,&nbsp;Hidenori Arai","doi":"10.1002/rco2.70002","DOIUrl":"https://doi.org/10.1002/rco2.70002","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator (SPPARMα), has positive effects on liver-related markers (e.g., liver stiffness determined by magnetic resonance elastography and alanine aminotransferase) in the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Patients with MASLD reportedly have a high rate of muscle mass loss; hence, the prevention and treatment of sarcopenia is important for patients with MASLD. PPARα may be involved in the expression of carnitine and myostatin, which are known muscle-related markers. We conducted a post-hoc analysis of the PEMA-FL study to investigate the effects of pemafibrate on carnitine and myostatin levels.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The PEMA-FL study, a double-blind, placebo-controlled, randomized, multicenter, Phase 2 trial, randomized 118 patients to either Pemafibrate 0.4 mg/day or placebo (1:1) group (orally, twice daily for 72 weeks). This post-hoc analysis examined the percentage change in total carnitine, free carnitine, acylcarnitine, and myostatin in the pemafibrate group compared to those in the placebo group. We examined the correlation between percentage changes in carnitine and myostatin levels.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pmafibrate significantly increased serum total carnitine and free carnitine levels from baseline compared to placebo at Week 48 (treatment difference 24.2%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001, 27.3%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001, respectively) with similar trends for serum acylcarnitine (treatment difference 10.7%). Pemafibrate significantly reduced plasma myostatin levels at Week 72 (treatment difference −11.0%; &lt;i&gt;p&lt;/i&gt; &lt; 0.01) from baseline. Analysis of the significant changes in free carnitine and myostatin levels by subgroups showed similar changes in almost all subgroups. The percent changes in the serum total carnitine, free carnitine and acylcarnitine, and plasma myostatin levels at 12 weeks demonstrated no obvious correlations (&lt;i&gt;r&lt;/i&gt; = 0.337, &lt;i&gt;r&lt;/i&gt; = 0.358, &lt;i&gt;r&lt;/i&gt; = 0.077, respectively).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pemafibrate increased the serum carnitine and decreased plasma myostatin levels in patients with MASLD, which may have potential application in the development and progression of sarcopenia, but there are no results on the effect on muscle mass. Further research is warranted to determine whether these changes in physiology can lead to clinical benefits in the prevention or treatmen","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699005","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":"Correction to “Overexpression of thioredoxin-2 attenuates age-related muscle loss by suppressing mitochondrial oxidative stress and apoptosis”","authors":"","doi":"10.1002/rco2.70003","DOIUrl":"https://doi.org/10.1002/rco2.70003","url":null,"abstract":"<p>\u0000 <span>Tang, H.</span>, <span>Kim, M.</span>, <span>Lee, M.</span>, <span>Baumann, K.</span>, <span>Olguin, F.</span>, <span>He, H.</span>, <span>Wang, Y.</span>, <span>Jiang, B.</span>, <span>Fang, S.</span>, <span>Zhu, J.</span>, <span>Wang, K.</span>, <span>Xia, H.</span>, <span>Gao, Y.</span>, <span>Konsker, H. B.</span>, <span>Fatodu, E. A.</span>, <span>Quarta, M.</span>, <span>Blonigan, J.</span>, <span>Rando, T. A.</span>, and <span>Shrager, J. B.</span> (<span>2022</span>) <span>Overexpression of thioredoxin-2 attenuates age-related muscle loss by suppressing mitochondrial oxidative stress and apoptosis</span>. <i>JCSM Rapid Communications</i>, <span>5</span>: <span>130</span>–<span>145</span>, https://doi.org/10.1002/rco2.57.\u0000 </p><p>We failed to include funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR73248) to TAR in the Acknowledgements.</p><p>We apologize for this error.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689275","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":"Malnutrition Risk and the Psychological Burden of Anorexia and Cachexia in Patients With Advanced Cancer","authors":"Rony Dev,&nbsp;Patricia Bramati,&nbsp;Marvin Omar Delgado Guay,&nbsp;Bryan Fellman,&nbsp;Ahsan Azhar,&nbsp;Michael Tang,&nbsp;Jegy Tennison,&nbsp;Josue Becerra,&nbsp;Sonal Admane,&nbsp;Shalini Dalal,&nbsp;David Hui,&nbsp;Egidio Del Fabbro,&nbsp;Eduardo Bruera","doi":"10.1002/rco2.70001","DOIUrl":"https://doi.org/10.1002/rco2.70001","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patients with advanced cancer are at risk for malnutrition and anorexia-cachexia syndrome. The study objective was to determine the frequency of these conditions in patients evaluated in an outpatient supportive care clinic (SCC).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;One hundred patients with cancer were prospectively enrolled to complete a cross-sectional one-time survey. We collected patient demographics, cancer diagnosis, weight history and height and Zubrod performance status from electronic health records. Patients completed the Functional Assessment of Anorexia Therapy–Anorexia/Cachexia Subscale (FAACT-A/CS) questionnaire, the Edmonton Symptom Assessment Scale (ESAS), the Patient-Generated Subjective Global Assessment–Short Form (PG-SGA-SF), the Hospital Anxiety and Depression Scale (HADS) and a Body Image Scale (BIS). A PG-SGA-SF cut-off of ≥ 6 indicated malnutrition risk, and loss of appetite was defined as either ESAS ≥ 3 or FAACT-ACS ≤ 37.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of the 165 patients approached, 100 (61%) completed the survey. The average (SD) age was 61.6 years old (11.5). The majority were female (52%), White (75%) and married (80%). The most common cancers were gastrointestinal (22%) and genitourinary (21%). Sixty-one per cent (61%) screened positive for risk of malnutrition (PG-SGA-SF ≥ 6), anorexia was noted in 60% (ESAS ≥ 3) and 53% (FAACT-A/CS ≤ 37) of patients, 10% of patients were noted to have a body mass index &lt; 18.5, and 28% had body image dissatisfaction (BIS ≥ 10). Documented &gt; 5% weight loss over the past 6 months was noted in 49%; 61% noted &gt; 10% lifetime weight loss, relative to usual adult body weight or at time of diagnosis. Patients with anorexia (FAACT-ACS ≤ 37) compared with no anorexia reported significantly higher HADS anxiety score (4.4 vs. 3.2, &lt;i&gt;p&lt;/i&gt; = 0.04), depression (5.9 vs. 3.5, &lt;i&gt;p&lt;/i&gt; = 0.001), body image distress (BIS 7.2 vs. 4.9, &lt;i&gt;p&lt;/i&gt; = 0.03) and worse appetite (ESAS 1.4 vs. 0.6, &lt;i&gt;p&lt;/i&gt; = 0.02). Symptoms including depression, anxiety and body image distress were not significantly different between patients with either a history of &gt; 10% lifetime weight loss or &gt; 5% weight loss over 6 months.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Malnutrition risk was noted in roughly 60% of patients with advanced cancer. Inclusion of patients' body mass index to malnutrition or cachexia criteria resulted in underdiagnosis. Subjective symptoms of anorexia, but not objective weight loss, was significantly associated w","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646230","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":"Linking Circulating Irisin and Type 2 Diabetes: A Systematic Review and Meta-Analysis","authors":"E. Aminov,&nbsp;P. Folan,&nbsp;A. Pisconti","doi":"10.1002/rco2.70000","DOIUrl":"https://doi.org/10.1002/rco2.70000","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Type II diabetes (T2DM) is one of the most prevalent metabolic disorders, and its multisystemic health consequences are widely known. Due to skeletal muscle's ability to sequester a vast amount of glucose, muscle function and exercise have become a subject of much research into strategies to prevent and treat T2DM. Myokines are bioactive molecules released by muscle during contraction and involved in several biological processes such as metabolism, inflammation and behaviour. Irisin, a recently discovered myokine, has been implicated in a vast array of physiological roles, including the ability to induce fat beiging. Since beige and brown fat both serve important roles in metabolic regulation, irisin's role in the context of T2DM is the subject of ongoing investigations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We systematically reviewed articles indexed in PubMed, Scopus and Web of Science that were published between 2011 and 2024 and compared circulating irisin levels in patients affected by T2DM and healthy subjects. As part of our systematic review of the literature, we performed meta-analysis of the data across all included articles, as well as stratified by body mass index (BMI), country of origin and by average irisin concentration in the control group.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We discovered great variability across the included studies in the average irisin levels detected, which spanned four orders of magnitude, hence the attempt at reducing variability by stratifying based on average levels in the control group. While the statistical power of our meta-analysis was decreased by the great variability in reported irisin concentrations, we nonetheless detected a consistent trend of decreased irisin concentration in T2DM patients compared with healthy controls, regardless of BMI, country of origin or average irisin concentration in the control group.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;With almost 60 articles included, ours is the first extensive systematic review and meta-analysis of irisin in T2DM, yet a highly statistically significant association between circulating irisin levels and T2DM could not be established due to the great variability of the data across include articles. Nonetheless, we noticed a trend that is independent of BMI, suggesting a direct relationship between T2DM and irisin that is likely not secondary to diabetic sarcopenia. While our work encourages further research into irisin's potential role in T2DM pathogenesis, the reproducibility of i","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612464","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":"Low Muscle Mass and Treatment Tolerance in Patients With Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis","authors":"E. N. Stanhope,&nbsp;S. N. Thomsen,&nbsp;J. E. Turner,&nbsp;C. M. Fairman,&nbsp;I. M. Lahart","doi":"10.1002/rco2.115","DOIUrl":"https://doi.org/10.1002/rco2.115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Upper gastrointestinal (GI) cancers carry notable mortality risks. While systemic therapies are vital for their management, they are often hindered by adverse events (AE), which can compromise their effectiveness. The presence of low skeletal muscle mass (LSMM) may be linked with the prevalence of AE and could potentially undermine treatment tolerance by impacting drug metabolism. The primary objective of this systematic review and meta-analysis was to evaluate the association between LSMM and the risk of grades 3 and 4 AE and treatment discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Studies investigating the association between skeletal muscle mass and AE or treatment tolerability in adult patients diagnosed with upper GI cancer scheduled to undergo systemic treatment were eligible. The primary outcomes were grades 3 and 4 AE and treatment discontinuations. Four electronic databases were systematically searched with no date restrictions on 10 October 2022. Data were analysed via random-effects meta-analyses, and the risk of bias was assessed using the risk of bias in non-randomised studies—of exposure (ROBINS-E) appraisal tool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 50 eligible publications from 49 studies. Our meta-analyses revealed evidence of a higher risk of grades 3 and 4 AE (RR 1.44, 95% CI 1.23–1.68, <i>N</i> = 13) and treatment discontinuation (RR 2.39, 95% CI 1.87–3.07, <i>N</i> = 11) in LSMM versus non-LSMM. Secondary analyses revealed an increased risk of fatigue, febrile neutropenia, intestinal pneumonia, stomatitis and thrombocytopenia in LSMM. However, 92% of studies assessing grades 3 and 4 AE and 73% of studies examining treatment discontinuation had a very high risk of bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LSMM in patients with upper GI cancer is associated with a higher risk of grades 3 and 4 AE and the discontinuation of systemic cancer treatment. The high risk of bias should be considered in the interpretation of these findings. Further evaluation of the association between LSMM and treatment tolerability in confirmatory, prospective studies is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431214","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":"Intramuscular CMT-167 Tumours Produce a Mild Cachexia Phenotype in C57BL/6J Mice","authors":"Bryan C. Remaily,&nbsp;Trang T. Vu,&nbsp;Justin Thomas,&nbsp;Kyeongmin Kim,&nbsp;Camille Stanton,&nbsp;Zhiliang Xie,&nbsp;Lauren Granchie,&nbsp;Millennium Manna,&nbsp;Paul Gregorevic,&nbsp;Xiaokui Mo,&nbsp;Jeovanna Lowe,&nbsp;Jill A. Rafael-Fortney,&nbsp;Samuel K. Kulp,&nbsp;Latha P. Ganesan,&nbsp;Dwight H. Owen,&nbsp;Thomas A. Mace,&nbsp;Christopher C. Coss,&nbsp;Mitch A. Phelps","doi":"10.1002/rco2.117","DOIUrl":"https://doi.org/10.1002/rco2.117","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without losses in adipose tissue. Cancer cachexia is an underrecognized syndrome that impacts ~50% of all cancer patients and accounts for up to ~20% of all cancer deaths. Lung cancer remains one of the deadliest cancers in the United States with an estimated 137 000 deaths in the year 2021 alone. Lung cancer is highly comorbid with cancer cachexia. Pre-clinical models are heavily relied upon to study both lung cancer and cancer cachexia; however, there is a need to develop novel models to study the relationship between the two diseases. We therefore characterized the cachexia phenotype in the CMT-167 syngeneic lung cancer model.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Male C57BL6/J mice, aged 8–10 weeks, were administered an intramuscular (IM) injection of either 0.5 × 10&lt;sup&gt;6&lt;/sup&gt; CMT-167 cells or vehicle. Clinically relevant features of cancer cachexia were assessed 23 days after CMT-167 cell administration in tumour bearing mice by assessment of terminal skeletal muscle and adipose tissue mass, gastrocnemius myofiber cross sectional area (CSA), circulating biomarkers of cachexia, and skeletal muscle E3 ubiquitin ligase mRNA. A single intravenous dose pharmacokinetic study of pembrolizumab was completed to assess tumour status influence upon antibody pharmacokinetics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Compared to tumour free (TF) mice, we observed lower terminal tumour-adjusted bodyweight, adipose tissue mass, gastrocnemius mass, quadriceps mass, and gastrocnemius myofiber CSA. CMT-167 tumour bearing (TB) mice did not lose bodyweight relative to starting weight, but instead failed to gain as much weight as TF controls. CMT-167 TB mice exhibited increased concentrations of circulating markers of cachexia and muscle wasting, such as IL-6 and TNF-&lt;i&gt;α&lt;/i&gt;, although there was no difference in transcription of E3 ubiquitin ligases &lt;i&gt;Trim63&lt;/i&gt; (MuRF-1) and &lt;i&gt;Fbxo32&lt;/i&gt; (atrogin-1) in skeletal muscle compared to TF mice. CMT-167 TB mice exhibited increased catabolic clearance (CL) of the human IgG4 anti-PD-1, pembrolizumab, agreeing with published literature showing increased CL of immune checkpoint inhibitors in cachectic populations. Comparing the IM CMT-167 model to historical data with the well-established IM Lewis Lung Carcinoma model, CMT-167 TB mice displayed a less severe cachectic phenotype in terms of bodyweight and skeletal muscle effects.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362815","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 Dynamic Time Warping Extension to Consensus Weight-Based Cachexia Criteria Improves Prediction of Cancer Patient Outcomes","authors":"Noah Forrest,&nbsp;Steven Tran,&nbsp;Khizar R. Nandoliya,&nbsp;Ethan J. Houskamp,&nbsp;Tomasz Gruchala,&nbsp;Vijeeth Guggilla,&nbsp;Zequn Sun,&nbsp;Rimas Lukas,&nbsp;Derek Wainwright,&nbsp;Al'ona Furmanchuk,&nbsp;Jodi L. Johnson,&nbsp;Ishan Roy,&nbsp;Theresa L. Walunas","doi":"10.1002/rco2.107","DOIUrl":"https://doi.org/10.1002/rco2.107","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cachexia is a complex syndrome that impacts up to half of patients with cancer. Criteria systems have been developed for the purpose of diagnosing and grading cachexia severity in clinical settings. One of the most widely known is those developed by Fearon et al. in 2011, which utilizes body mass loss and body mass index (BMI) to determine the presence and extent of cachexia. One limitation of this system and other clinical cachexia scales is the lack of systematic methods for assessing cachexia severity longitudinally. We sought to develop an extension to the 2011 consensus criteria that categorizes cancer patients with respect to their temporal cachexia progression and assess its predictive capacity relative to the current time-agnostic system.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Two cancer cohorts were identified in electronic health record data: lung cancer and glioblastoma. We extracted weight and BMI measures from the time of cancer diagnosis until death or loss to follow-up and computed cachexia severity according to the consensus criteria. Subgroups of cachexia progression were uncovered using dynamic time warping (DTW) followed by unsupervised clustering. This system and baseline consensus criteria measurements were each assessed for their ability to stratify patient outcomes utilizing Kaplan–Meier curves and Cox proportional hazards and subsequently compared with model concordance and inverse probability of censoring weighting (IPCW).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Significant differences were observed in overall survival Kaplan–Meier curves of 1023 patients with lung cancer when stratified by baseline cachexia classification (&lt;i&gt;p&lt;/i&gt; = 0.0002, N events = 592) but not in a cohort of 545 patients with glioblastoma (&lt;i&gt;p&lt;/i&gt; = 0.16, N events = 353). DTW uncovered three patterns of cachexia progression in each subgroup with features described as ‘smouldering’, ‘rapid with recovery’ or ‘persistent/recurrent’. Significant differences were observed in Kaplan–Meier curves when stratified by cachexia longitudinal patterns in lung cancer (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and glioblastoma (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Adjusted hazards ratios comparing the ‘persistent/recurrent’ cluster to referent subgroups in Cox models were 4.8 (4.1–5.8, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and 1.9 (1.4–2.4, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) among patients with lung cancer and glioblastoma, respectively. Areas under the curve at multiple time points and Cox model concordances were greater when patients were stratified by progression pattern compared with baseline consensus criteria.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389454","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":"Creatinine Muscle Index as a Novel Muscle Mass Indicator in Patients With Chronic Kidney Disease","authors":"Hiroki Nobayashi,&nbsp;Go Kanzaki,&nbsp;Aoi Okubo,&nbsp;Nobuo Tsuboi,&nbsp;Takashi Yokoo","doi":"10.1002/rco2.116","DOIUrl":"https://doi.org/10.1002/rco2.116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The early detection of muscle loss in patients with chronic kidney disease (CKD) is crucial. The creatinine muscle index (CMI, mg/day/1.73 m²), which is calculated as the product of serum creatinine, is easily available in daily care and estimates the muscle mass. However, the association between CMI and muscle mass has not been fully assessed. We aimed to investigate whether CMI can serve as a predictor of muscle mass in patients with CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included patients with CKD undergoing kidney biopsy and plain computed tomography (CT) to assess the kidney morphology. Muscle mass was assessed using the psoas muscle index, determined by dividing the cross-sectional psoas muscle area at the L3 level, measured by manual tracing on pre-biopsy CT, by the participant's height (cm²/m²).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 159 participants (84 male [52.8%], mean age 51.7 ± 16 years) were included. CMI was positively correlated with PMI in men (<i>r</i> = 0.37, <i>p</i> &lt; 0.01) and women (<i>r</i> = 0.56, <i>p</i> &lt; 0.01). The prevalence of low muscle mass was 55 (65.5%) in men and 44 (58.7%) in women. The odds ratios (ORs) and 95% confidence intervals (CIs) for low muscle mass were significantly higher in Tertile 1 of CMI than in Tertile 3 in both men and women (OR, 5.37 [95% CI, 1.32–21.8] in men; OR, 7.31 [95% CI, 1.38–38.6] in women) after adjusting for age, body mass index and co-morbidities (hypertension and diabetes). According to receiver operating characteristics curves, the optimal cut-off value of CMI for low muscle mass was 1079 mg/day/1.73 m² (area under the curve 0.69 [95% CI: 0.57–0.81]; sensitivity, 0.78; specificity, 0.62) in men and 693 mg/day/1.73 m² (area under the curve 0.74 [95%CI: 0.63–0.85]; sensitivity, 0.57; specificity, 0.90) in women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMI is significantly associated with muscle mass in patients with CKD. Our findings suggest the utility of CMI for screening the muscle mass in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114772","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":"Cardiac Cachexia and the Associations to the Microbiome: State-of-the-Science Review","authors":"Kelley M. Anderson,&nbsp;Amanda Schmitt,&nbsp;William S. Weintraub,&nbsp;Rebecca Scally,&nbsp;Tomoko Y. Steen","doi":"10.1002/rco2.114","DOIUrl":"https://doi.org/10.1002/rco2.114","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cardiac cachexia is a late manifestation of advanced heart failure, with a 5%–15% prevalence. A diagnosis of cardiac cachexia is not simply another complication of heart failure; clinical consequences of cachexia are impaired physical function, fatigue, poor quality of life and independently associated with heart failure severity, adverse cardiovascular and non-cardiovascular outcomes, longer length of hospital stays and increased mortality. Although it is well established that cardiac cachexia is associated with poor outcomes, there remains a lack of evidence describing the underlying mechanisms that has resulted in limited impactful treatment modalities. Contemporary explorations describe the association of the gut microbiome related to many health conditions, including heart failure. Preclinical and clinical studies are defining the role of the microbiome and the associations to heart failure and comorbidities including cardiac cachexia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this review, we summarize the relevant literature to (1) describe the diagnosis and evaluation of cachexia in individuals with heart failure; (2) provide an overview of the heart–gut axis; (3) report on the gut microbiome as a mediator of cardiac cachexia with a focus on inflammation and protein loss; (4) detail the clinical characterizations and manifestations of cardiac cachexia; (5) review current treatment modalities for cardiac cachexia and their limitations; and (6) provide recommendations for future lines of inquiry for heart failure–related cachexia and the microbiome.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Current clinical and animal studies are developing the science to expand our understanding of the association of the microbiome to the clinical expression of cardiovascular conditions, including heart failure and related conditions, including cachexia. Elucidating mechanisms of cachexia will provide the foundational evidence to improve treatment approaches. Available treatments are limited and do not meaningfully impact the illness experience of patients with heart failure and cachexia. Improving our understanding of the innovative concept of the heart–gut axis has the potential for significant clinical advances in developing novel diagnostic and therapeutic approaches for heart failure and for evaluating a common pathway for cachexia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this review, we discuss the characteristics, evaluation, impact on prognosis and therapeutic interventions of cachexia an","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114771","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}