JCSM rapid communications最新文献

{"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}

{"title":"Low-Intensity Exercise Protects Skeletal and Cardiac Muscle Against Cancer-Mediated Muscle Wasting via Regulation of Autophagy and Inflammation","authors":"Louisa Tichy,&nbsp;Traci L. Parry","doi":"10.1002/rco2.103","DOIUrl":"https://doi.org/10.1002/rco2.103","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;Up to 80% of cancer patients suffer from skeletal and cardiac muscle wasting, also known as cancer cachexia. This metabolic wasting syndrome is responsible for up to one-third of deaths in these cancer patients. Treatment options to attenuate muscle loss are limited. However, research shows that exercise interventions can slow tumour development and preserve muscle mass and function. Questions remain regarding the most effective modalities of exercise as a preventative intervention against cancer-mediated muscle wasting. The purpose of this study was to determine if low-intensity treadmill exercise can act as a protective measure and intervention against cancer-mediated muscle wasting in male mice.&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 LC3 Tg+ and WT mice were randomly separated into four groups: sedentary non-tumour bearing (SED + NT), sedentary tumour bearing (SED + T), low-intensity treadmill exercise non-tumour bearing (TM + NT) and low-intensity treadmill exercise tumour bearing (TM + T). Mice were implanted with tumour cells (T group; 5 × 10&lt;sup&gt;5&lt;/sup&gt; LLC cells in flank) or remained non-tumour (NT) for 4 weeks. During the 4 weeks, mice underwent a low-intensity treadmill training protocol (TM) or remained sedentary (SED). Grip strength, echocardiography and tumour growth was assessed, and inflammatory and autophagic protein pathways in skeletal and cardiac muscle tissue were investigated.&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;SED + T mice exhibited worst grip strength and cardiac function (fractional shortening). Coinciding with worse skeletal and cardiac function, inflammatory and autophagic pathways were abnormally upregulated in SED + T mice compared with NT controls (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Low-intensity exercise protected musculature by cardiac function and grip strength in TM + T compared with SED + T mice. Low-intensity exercise attenuated inflammation and autophagy in TM + T mice. Additionally, treadmill exercise resulted in significantly smaller tumour mass and volume (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) in the TM + T compared with SED + T 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;Our data indicated cardioprotective, myoprotective and tumour-suppressive effects of low-intensity treadmill exercise in tumour bearing mice. Low-intensity exercise preserved skeletal and cardiac muscle function and inhibited tumour growth by regulating autophagy and inflammation. Therefore, low-intensity treadmill exercise may be an effective, affordable and accessible adjuvant treatment for cancer","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121506","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":"Why Do Cancer Patients Die?","authors":"Timon Rausch,&nbsp;Thorsten Cramer","doi":"10.1002/rco2.113","DOIUrl":"https://doi.org/10.1002/rco2.113","url":null,"abstract":"&lt;p&gt;Cancer is a significant contributor to mortality on a global scale. But what actually causes a cancer patient to die? Here, we summarize the elegant review “Why do cancer patients die?” from Boire and colleagues [&lt;span&gt;1&lt;/span&gt;], highlighting severe acute events, systemic factors, and their underlying causes in this context.&lt;/p&gt;&lt;p&gt;Cancer metastasis is often cited as the primary cause of cancer-related mortality [&lt;span&gt;2&lt;/span&gt;]. However, this term is over simplistic, not completely precise and not largely supported by published literature. While it is true that patients with metastatic cancer are more likely to die than those with locally confined disease, cancer is intriguingly complex and results in a variety of symptoms, including acute single events or patient deterioration through systemic (organ) dysfunction. To effectively mitigate the destructive impact of cancer, it is essential to gain a deeper understanding of the physiological responses involved and identify more precisely the various cancer-related causalities.&lt;/p&gt;&lt;p&gt;Most advanced cancers can be considered as a chronic and systemic disease. However, it is likely that up to half of the cancer-induced deaths are functionally related to severe events such as vascular coagulation and cardiac failure, obstruction of vital organs, bacterial infection, or paraneoplastic syndromes. For instance, patients with cancer have an elevated risk of thromboembolic events, which may lead acutely to fatal strokes or pulmonary emboli and chronically to coronary heart disease and, subsequently, heart failure. Furthermore, congestive heart failure may also occur due to excessive loss of cardiac muscle, a phenomenon associated with and often caused by cancer cachexia. In addition, growing tumours can impair vital organ function. This can particularly be observed in primary brain cancers, where uncontrolled growth increases intracranial pressure, which can ultimately cause irreversible brain damage. A similar phenomenon can be observed in the lung, where pulmonary metastases can reduce gas exchange, resulting in severe respiratory distress. Because cancer patients often have compromised immune systems, both from the disease itself and from cancer therapy, they are at an increased risk for bacterial, viral, or fungal infections that can cause life-threatening complications. Moreover, paraneoplastic syndromes can irreversibly damage critical organs as a consequence of tissue dysfunction in the surrounding area of the tumour. For example, an inappropriate production of pro-inflammatory cytokines, hormones, or antibodies can result in severe adverse effects, potentially leading to critical organ damage and ultimately, death. Despite the principle objective of cancer treatments to target tumour cells, almost every therapeutic agent has unwanted adverse effects, including acute neutropenia (potentially leading to bacterial sepsis) or platelet depletion, which can also be life-threatening in some cases.&lt;/p&gt;&lt;p&gt;N","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"80-81"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187207","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 Gene-Therapy Responsive Blood Biomarkers in mdx Mouse Model","authors":"Camilla Johansson,&nbsp;Jessica F. Boehler,&nbsp;Kristy J. Brown,&nbsp;Zaïda Koeks,&nbsp;Esther J. Schrama,&nbsp;Nienke van de Velde,&nbsp;Jan J. G. M. Verschuuren,&nbsp;Erik H. Niks,&nbsp;Pietro Spitali,&nbsp;Cristina Al-Khalili Szigyarto","doi":"10.1002/rco2.112","DOIUrl":"https://doi.org/10.1002/rco2.112","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Identifying serum biomarkers that reflect the restoration of dystrophin in skeletal muscle is important for evaluating the effect of dystrophin-restoring therapies in preclinical and clinical trials. Many potential blood biomarkers have been identified in Duchenne muscular dystrophy (DMD) patients, which change with disease progression or respond to pharmacological treatment. In this study, it was suggested that a panel of such blood biomarker candidates could be used to monitor dystrophin rescue in &lt;i&gt;mdx&lt;/i&gt; mice treated with microdystrophin based therapies.&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;Plasma samples from &lt;i&gt;mdx&lt;/i&gt; mice treated with the microdystrophin therapy SGT-001 were analysed with an antibody suspension bead array consisting of 87 antibodies. The array targets 83 unique proteins previously identified as biomarker candidates for DMD. Each sample was assayed at two different plasma dilutions to cover a broader concentration range. Protein concentrations estimated as Median fluorescent intensities (MFI) were correlated to dystrophin expression in muscle tissue, as measured by immunohistochemistry and Western blot. Thirteen of the targets were selected and analysed in a DMD and Becker muscular dystrophy (BMD) longitudinal natural history cohort using a suspension bead array.&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;Ten proteins were found to be significantly elevated in untreated &lt;i&gt;mdx&lt;/i&gt; mice compared with C57 wild-type mice and to correlate with dystrophin expression (Spearman's correlation, FDR &lt; 0.05) upon gene transfer in &lt;i&gt;mdx&lt;/i&gt; mice. Translatability of these biomarkers from animal models to patients was evaluated by exploring abundance trajectories over time in both DMD and BMD patients and association with dystrophin expression in BMD patients. Consistent with the observations in mouse, six of these biomarker candidates were more abundant in DMD patients compared with controls, and six were also differentially abundant between BMD and DMD patients. Among them, serum titin was shown to be associated with dystrophin expression in BMD patients, having a steeper decline over time in patients with low dystrophin expression in tibialis anterior compared with patients with high expression. Myosine light chain 3 had a steeper decline with time in DMD patients compared with BMD patients.&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;The 10 biomarker candidates identified in mouse plasma are related to muscle contraction, glycolysis, microtubule formation and protein de","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"187-198"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187045","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 Natural History Study of Hindlimb Physiology and Histopathology in a Heterozygous OPMD Mouse Model","authors":"Jorge Miguel Amaya,&nbsp;Sofie van Zanen-Gerhardt,&nbsp;Ernst Suidgeest,&nbsp;Jessica C. de Greef,&nbsp;Louise van der Weerd,&nbsp;Donnie Cameron,&nbsp;Christina J. J. Coenen de Roo,&nbsp;Maaike van Putten,&nbsp;Vered Raz","doi":"10.1002/rco2.101","DOIUrl":"https://doi.org/10.1002/rco2.101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy. OPMD is caused by a short alanine expansion in the gene encoding for poly(A) binding protein nuclear 1 (PABPN1) forming insoluble nuclear aggregates. OPMD patients are predominantly heterozygous, and the knock-in <i>Pabpn1</i>^+/A17 mouse, which expresses one copy of the expanded <i>Pabpn1</i> gene under the PABPN1 promoter genetically, mimics OPMD. Insights into the A17/+ mouse model are necessary to evaluate its preclinical value and test therapeutics for OPMD. Here, we performed a natural disease history study for the A17/+ model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We combined muscle force measurements of the <i>tibialis anterior</i> with magnetic resonance imaging (MRI) measurements of the calf muscles made in 4-, 8- and 12-month-old wild-type and A17/+ mice. These measures were complemented by muscle histopathology staining and image quantification to detect PABPN1 aggregates and to assess muscle wasting. Statistical significance between genotypes over the three time points was assessed using ANOVA or Student's <i>t</i> test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PABPN1 nuclear aggregates were found in the 12-month-old A17/+ mice at similar quantities of ~2% across hindlimb muscles. We did not observe changes in muscle strength of the <i>tibialis anterior</i> in A17/+ mice. MRI analyses of hindlimb muscles revealed no metabolic difference, no fatty infiltration and limited muscle atrophy between A17/+ and +/+ mice. The <i>plantaris</i> muscle in A17/+ showed 30% atrophy at 12 months of age, which was corroborated by a 30% myofiber shift in the myosin heavy chain −2A to −2B ratio. Histopathologic staining did not reveal muscle wasting in the hindlimb muscles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite the presence of PABPN1 insoluble aggregates in hindlimb muscles, muscle involvement in the 12-month-old A17/+ mice was limited. Our results query the usefulness of A17/+ hindlimb muscles for preclinical studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"107-116"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187030","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 “Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials”","authors":"","doi":"10.1002/rco2.110","DOIUrl":"https://doi.org/10.1002/rco2.110","url":null,"abstract":"<p>\u0000 <span>Fairman, C. M.</span>, <span>Lønbro, S.</span>, <span>Cardaci, T. D.</span>, <span>VanderVeen, B. N.</span>, <span>Nilsen, T. S.</span>, and <span>Murphy, A. E.</span> (<span>2022</span>) <span>Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials</span>. <i>JCSM Communications</i>, <span>5</span>: <span>52</span>–<span>67</span>, https://doi.org/10.1002/rco2.56.</p><p>The Ethics statement section for this article was missing. The below ethics statement has been added to the article:</p><p><b>Ethics Statement</b></p><p>The authors have nothing to report.</p><p>We apologize for this error.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"186"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187028","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}