Diet-induced obesity does not exacerbate cachexia in male mice bearing Lewis-lung carcinoma tumors.

Cachexia is a muscle-wasting syndrome commonly observed in patients with cancer, which can significantly worsen clinical outcomes. Because of a global rise in obesity, the coexistence of cachexia in obese individuals poses unique challenges, with the impact of excessive adiposity on cachexia severity and underlying pathophysiology not well defined. Understanding the interplay between cachexia and obesity is crucial for improving diagnosis and treatment strategies for these patients; therefore, the present study examined differences in cachexia between lean and obese mice bearing Lewis lung carcinoma (LLC) tumors. Nine-week-old, male C57Bl6J mice were placed on either a chow or a high-fat diet (HFD) for 9 wk. After the diet intervention, mice were inoculated with LLC or vehicle. Markers of cachexia, such as body and muscle loss, were noted in both chow and HFD groups with tumors. Tumor weight of HFD animals was greater than that of chow. LLC tumors reduced gastrocnemius, plantaris, and soleus mass, regardless of diet. The tibialis anterior and plantaris mass and cross-sectional area of type IIb/x fibers in the gastrocnemius were not different between HFD-chow, HFD-tumor, and chow-tumor. Using RNA sequencing (RNA-seq) of the plantaris muscle from chow-tumor and HFD-tumor groups, we identified ∼400 differentially expressed genes. Bioinformatic analysis identified changes in lipid metabolism, mitochondria, bioenergetics, and proteasome degradation. Atrophy was not greater despite larger tumor burden in animals fed an HFD, and RNA-seq data suggests that partial protection is mediated through differences in mitochondrial function and protein degradation, which may serve as future mechanistic targets.NEW & NOTEWORTHY This study provides timely information on the interaction between obesity and cancer cachexia. Lean and obese animals show signs of cachexia with reduced body weight, adipose tissue, and gastrocnemius muscle mass. There was not significant wasting in the tibialis anterior, plantaris, or fast twitch fibers in the gastrocnemius muscle of obese animals with tumors. RNA-seq analysis reveals that obese tumor bearing animals had differential expression of mitochondria- and degradation-related genes, which may direct future studies in mechanistic research.

Variable body and tissue weight reporting in preclinical cachexia literature may alter study outcomes and interpretation.

Cancer cachexia is a multifactorial syndrome of body weight loss, muscle wasting and progressive functional decline, affecting many advanced cancer patients and leading to worsened clinical outcomes. Despite inherent limitations of many preclinical cachexia models, including large tumor burden, rapid tumor growth and young age of animals, these animal models are widely used and imperative for the study of cachexia mechanisms and experimental therapeutics. However, there are currently no guidelines for the reporting and representation of data in preclinical cachexia literature. We examined the current state of data reporting in publications using the colon-26 adenocarcinoma (C26) model of cachexia and compared statistical differences in reporting mechanisms using animals from our laboratory. We show that data reporting and representation in C26 preclinical cachexia literature are diverse, making comparison of study outcomes difficult. Further, different expression of body and tissue weights in our animals led to differential statistical significance, which could significantly alter data interpretation. This study highlights a need for consistent data reporting in preclinical cancer cachexia literature to effectively compare outcomes between studies and increase translatability to the human condition.

Comparison of the "Tall and Fall" Versus "Drop and Drive" Pitching Styles: Analysis of Major League Baseball Pitchers During a Single Season.

Background: Previous research has documented the proportion of "tall and fall" (TF) and "drop and drive" (DD) pitching styles among Major League Baseball (MLB) pitchers who underwent ulnar collateral ligament reconstruction (UCLR). The proportion of these 2 styles among all MLB pitchers remains unknown. Purpose: To determine the proportion of the TF and DD pitching styles in all rostered MLB pitchers during a single season as well as the proportion of TF and DD pitchers who sustained an upper extremity (UE) injury and those who underwent UCLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Pitcher demographic characteristics from the 2019 MLB season and pitching information were obtained via open-access sources. Two-dimensional video analysis was used to categorize the included pitchers into TF and DD groups. Statistical comparisons and contrasts were made using 2-tailed t tests, chi-square tests, and Pearson correlation analyses as appropriate. Results: Of the 660 MLB rostered pitchers in 2019 (age, 27.39 ± 3.51 years; body mass index, 26.34 ± 2.47 kg/m2; fastball velocity, 150.49 ± 3.99 kph [93.51 ± 2.48 mph]), 412 (62.4%) pitchers used the TF style and 248 (37.6%) pitchers used the DD style. Significantly more UE injuries were seen in the TF group compared with the DD group (112 vs 38 injuries, respectively; P < .001). Twelve pitchers underwent UCLR (TF, 10; DD, 2), representing a 1.8% UCLR rate among all pitchers. This was a second surgery for 2 pitchers, both of whom used the TF pitching style. Significantly more pitchers in the TF group than the DD group had undergone UCLR before 2019 (135 vs 56 pitchers, respectively; P = .005). Conclusion: The results of the present study demonstrated a higher prevalence of both UE injury and prior UCLR in TF pitchers. Further research is needed to explore the potential association between pitching style and UE injury.

Knowledge and Perceptions of Ulnar Collateral Ligament Injuries in Baseball Players: A Survey of NCAA Head Baseball Coaches.

Background: There is growing concern among sports medicine professionals regarding the increasing prevalence of ulnar collateral ligament (UCL) surgery in baseball players. At this time, it is unclear whether collegiate head baseball coaches possess adequate knowledge of UCL injuries. Purpose/Hypothesis: The purpose of this study was to assess the knowledge and perceptions of UCL injury among National Collegiate Athletic Association (NCAA) head baseball coaches. It was hypothesized that NCAA head baseball coaches would demonstrate misconceptions and knowledge disparities regarding UCL injury. Study Design: Cross-sectional study. Methods: An online 35-question survey was designed to assess NCAA head baseball coaches' knowledge of UCL injury. The survey included questions related to participant characteristics, UCL injury, biometric performance and pitching variables, throwing fatigue, surgical variables/performance outcomes, and collegiate athlete recruitment. A total of 788 NCAA head baseball coaches were asked to participate. Responses were analyzed and reported using descriptive statistics where appropriate. Statistical comparisons and contrasts were made using chi-square and Fisher exact tests. Results: A total of 103 NCAA head baseball coaches participated in the survey, representing a 13.1% response rate. Only 31% of respondents could correctly identify all UCL injury symptoms, and 93% recommended <8 weeks off from overhead throwing during the off-season. Previous elbow injury observation was associated with UCL symptom identification (χ2 = 10.614; P = .005). Regular access to an athletic trainer (P = .015) and regular access to a strength and conditioning coach (P = .004) were both associated with NCAA division status, with Division I programs having the most access. Neither sports medicine physician (P = .656) nor athletic trainer (P = .611) access was associated with the geographic location of the baseball program; however, strength and conditioning coach access was associated with geographic location (χ2 = 6.696; P = .010). Conclusion: This study demonstrates that limited UCL injury knowledge and various misconceptions exist among NCAA baseball head coaches. The majority of responding coaches recommended an amount of time off from overhead throwing during the off-season that may be inadequate and were unable to identify all symptoms associated with UCL injury, representing the most concerning findings of the present study.

Retrospective Analysis of Ulnar Collateral Ligament Reconstructions in Major League Baseball Pitchers: A Comparison of the "Tall and Fall" Versus "Drop and Drive" Pitching Styles.

Background: Previous pilot research has investigated differences in elbow valgus torque between the "tall and fall" (TF) and "drop and drive" (DD) pitching styles. Whether one of these pitching styles is associated with a greater rate of ulnar collateral ligament reconstruction (UCLR) is currently unknown. Purpose: To determine the proportion of Major League Baseball (MLB) pitchers using the TF and DD pitching styles who underwent UCLR over a 10-year period. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The demographic characteristics of pitchers who underwent UCLR between 2007 and 2017 were obtained via the open-source database MLB Player Analysis Tommy John Surgery List. Other information, such as previous UCLR and pitching videos and graphics, was obtained from other open-source databases. A comprehensive, 2-dimensional, kinesiology-based multicomponent definition of each pitching style was formulated and used to categorize the included pitchers into the TF and DD groups. Statistical comparisons and contrasts were made using chi-square and Pearson correlation tests. Results: Included were 223 MLB pitchers (mean ± SD age, 27.5 ± 3.6 years; body mass index [BMI], 27.6 ± 2.2; throwing velocity, 92.9 ± 2.6 mph [149.5 ± 4.2 km/h]) who underwent UCLR between 2007 and 2017. Of these pitchers, 162 were categorized as TF pitchers (72.6%) and 61 as DD pitchers (27.4%). Pitching velocity for injured pitchers was significantly correlated to BMI (P < .001). We found no significant associations of pitching style with year of UCLR (P = .941), BMI (P = .549), age (P = .647), handedness (P = .501), or average pitch velocity (P = .921). Conclusion: The study findings demonstrated that a higher proportion of UCL-injured MLB pitchers (72.6%) used the TF pitching style. Further research is needed to explore the potential association between pitching style and UCL injury.

Leucine Supplementation in Cancer Cachexia: Mechanisms and a Review of the Pre-Clinical Literature.

Cancer cachexia (CC) is a complex syndrome of bodily wasting and progressive functional decline. Unlike starvation, cachexia cannot be reversed by increased energy intake alone. Nonetheless, targeted nutritional support is a necessary component in multimodal syndrome management. Due to the highly catabolic nature of cancer cachexia, amino acid supplementation has been proposed. Interestingly, leucine has been found to increase protein synthesis and decrease protein degradation via mTORC1 pathway activation. Multiple pre-clinical studies have explored the impact of leucine supplementation in cachectic tumor-bearing hosts. Here, we provide an overview of leucine's proposed modes of action to preserve lean mass in cachexia and review the current pre-clinical literature related to leucine supplementation during CC. Current research indicates that a leucine-rich diet may attenuate CC symptomology; however, these works are difficult to compare due to methodological differences. There is need for further pre-clinical work exploring leucine's potential ability to modulate protein turnover and immune response during CC, as well as the impact of additive leucine on tumor growth.

Cardiac Remodeling in Cancer-Induced Cachexia: Functional, Structural, and Metabolic Contributors.

Cancer cachexia is a syndrome of progressive weight loss and muscle wasting occurring in many advanced cancer patients. Cachexia significantly impairs quality of life and increases mortality. Cardiac atrophy and dysfunction have been observed in patients with cachexia, which may contribute to cachexia pathophysiology. However, relative to skeletal muscle, little research has been carried out to understand the mechanisms of cardiomyopathy in cachexia. Here, we review what is known clinically about the cardiac changes occurring in cachexia, followed by further discussion of underlying physiological and molecular mechanisms contributing to cachexia-induced cardiomyopathy. Impaired cardiac contractility and relaxation may be explained by a complex interplay of significant heart muscle atrophy and metabolic remodeling, including mitochondrial dysfunction. Because cardiac muscle has fundamental differences compared to skeletal muscle, understanding cardiac-specific effects of cachexia may bring light to unique therapeutic targets and ultimately improve clinical management for patients with cancer cachexia.