Local Delivery of SBRT and IL12 by mRNA Technology Overcomes Immunosuppressive Barriers to Eliminate Pancreatic Cancer.

The immunosuppressive milieu in pancreatic cancer (PC) is a significant hurdle to treatments, resulting in survival statistics that have barely changed in 5 decades. Here we present a combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to pancreatic murine tumors. This treatment was effective against primary and metastatic models, achieving cures in both settings. IL-12 protein concentrations were transient and localized primarily to the tumor. Depleting CD4 and CD8 T cells abrogated treatment efficacy, confirming they were essential to treatment response. Single cell RNA sequencing from SBRT/IL-12 mRNA treated tumors demonstrated not only a complete loss of T cell exhaustion, but also an abundance of highly proliferative and effector T cell subtypes. SBRT elicited T cell receptor clonal expansion, whereas IL-12 licensed these cells with effector function. This is the first report demonstrating the utility of SBRT and IL-12 mRNA in PC. Statement of significance: This study demonstrates the use of a novel combination treatment consisting of radiation and immunotherapy in murine pancreatic tumors. This treatment could effectively treat local and metastatic disease, suggesting it may have the potential to treat a cancer that has not seen a meaningful increase in survival in 5 decades.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim is to identify what factors in the tumor microenvironment drive a fraction of rectal cancer patients to respond to radiotherapy. We also sought to distinguish potential biomarkers that would indicate a positive response to therapy and design combinatorial therapeutics to enhance radiotherapy efficacy. To address this, we developed an orthotopic murine model of rectal cancer treated with short course radiotherapy that recapitulates the bimodal response observed in the clinic. We utilized a robust combination of transcriptomics and protein analysis to identify differences between responding and nonresponding tumors. Our mouse model recapitulates human disease in which a fraction of tumors respond to radiotherapy (responders) while the majority are nonresponsive. We determined that responding tumors had increased damage-induced cell death, and a unique immune-activation signature associated with tumor-associated macrophages, cancer-associated fibroblasts, and CD8+ T cells. This signature was dependent on radiation-induced increases of Type I Interferons (IFNs). We investigated a therapeutic approach targeting the cGAS/STING pathway and demonstrated improved response rate following radiotherapy. These results suggest that modulating the Type I IFN pathway has the potential to improve radiation therapy efficacy in RC.

CD73 and PD-L1 dual blockade amplifies antitumor efficacy of SBRT in murine PDAC models.

BACKGROUND: Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model. METHODS: We assessed the combination of systemic blockade of CD73/PD-L1 and local SBRT on tumor growth in primary pancreatic tumors, and investigated systemic antitumor immunity using a metastatic murine model bearing both orthotopic primary pancreatic tumor and distal hepatic metastases. Immune response was quantified by flow cytometric and Luminex analyses. RESULTS: We demonstrated that blockade of both CD73 and PD-L1 significantly amplified the antitumor effect of SBRT, leading to superior survival. The triple therapy (SBRT+anti-CD73+anti-PD-L1) modulated tumor-infiltrating immune cells with increases of interferon-γ+CD8+ T cells. Additionally, triple therapy reprogramed the profile of cytokines/chemokines in the tumor microenvironment toward a more immunostimulatory phenotype. The beneficial effects of triple therapy are completely abrogated by depletion of CD8+ T cells, and partially reversed by depletion of CD4+ T cells. Triple therapy promoted systemic antitumor responses illustrated by: (1) potent long-term antitumor memory and (2) enhanced both primary and liver metastases control along with prolonged survival.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim is to identify what factors in the tumor microenvironment drive a fraction of rectal cancer patients to respond to radiotherapy. We also sought to distinguish potential biomarkers that would indicate a positive response to therapy and design combinatorial therapeutics to enhance radiotherapy efficacy. To address this, we developed an orthotopic murine model of rectal cancer treated with short course radiotherapy that recapitulates the bimodal response observed in the clinic. We utilized a robust combination of transcriptomics and protein analysis to identify differences between responding and nonresponding tumors. Our mouse model recapitulates human disease in which a fraction of tumors respond to radiotherapy (responders) while the majority are nonresponsive. We determined that responding tumors had increased damage-induced cell death, and a unique immune-activation signature associated with tumor-associated macrophages, cancer-associated fibroblasts, and CD8 + T cells. This signature was dependent on radiation-induced increases of Type I interferons (IFNs). We investigated a therapeutic approach targeting the cGAS/STING pathway and demonstrated improved response rate following radiotherapy. These results suggest that modulating the Type I IFN pathway has the potential to improve radiation therapy efficacy in RC.

A case report of COVID-19 monitoring in the Austrian professional football league.

Since the beginning of the COVID -19 pandemic, many contact sport teams are facing major challenges to safely continue training and competition. We present the design and implementation of a structured monitoring concept for the Austrian national football league. 146 professional players from five clubs of the professional Austrian football league were monitored for a period of 12 weeks. Subjective health parameters, PCR- test results and data obtained from a geo-tracking app were collected. Simulations modelling the consequences of a COVID-19 case with increasing reproduction number were computed. No COVID -19 infection occurred during the observation period in the players. Infections in the nearer surroundings lead to increased perceived risk of infection. Geo tracking was particularly hindered due to technical problems and reluctance of users. Simulation models suggested a hypothetical shut-down of all training and competition activities. A structured monitoring concept can help to continue contact sports safely in times of a pandemic. Cooperation of all involved is essential. Trial registration: ID: DRKS00022166 15/6/2020 https://www.who.int/ictrp/search/en/ .

Medication Status and Gait Mechanics in Older Adults: A Multivariate Analysis.

BACKGROUND AND PURPOSE: Falls are the leading cause of unintentional deaths in older adults, with nearly one-third of adults older than 65 years falling annually. Previous work reveals that both medication status and gait changes are contributing factors to falls in older adults; however, it is unknown how these factors interact. Thus, the purpose of this investigation was to examine differences between gait biomechanics as a function of medication status in individuals older than 60 years with a self-reported history of falling. It was hypothesized that differences in gait mechanics would be observed as a function of the number of medications in these individuals. METHODS: A total of 384 participants, age, mean (SD) = 73.2 (4.2) years; height, mean (SD) = 173.09 (16.4) cm; mass, mean (SD) = 65.45 (5.78) kg, were recruited from across the Southwest United States (Texas, New Mexico, Arizona, Nevada, and California) by the Electronic Caregiver Mobile Fall Risk Assessment Laboratory. Data for cadence, gait velocity, stride length, swing time, and double-support time were collected using a Walkway gait analysis system. Factor analysis was employed to determine whether the gait characteristics were similar to those observed in previous studies. A multivariate analysis with a follow-up univariate analysis was employed to determine group differences in gait factors and variables according to medication number (≥4 medications, n = 262 vs ≤3 medications, n = 122). RESULTS: Results of the factor analysis reveal that the data analyzed in the current study are similar to those observed in previous studies, with cadence (factor loading coefficient [FLC] = 0.745), gait velocity (FLC = 0.922), stride length (FLC = 0.789 for left and 0.790 for right) loading positively on a "pace" factor, swing time (FLC = 0.728 for right and 0.683 for left), and double-support time (FLC= 0.723) loading positively on a "rhythm" factor. The results of the multivariate analysis of variance revealed differences in gait factors across groups according to medication status. Univariate follow-up tests reveal that double-support time is longer and stride length is shorter in persons taking 4 or more medications as compared with those on 3 or fewer medications. CONCLUSION: The findings of this study indicate that certain abnormal gait parameters in participants with a history of falls are associated with taking 4 or more medications. Future studies should examine the extent to which gait changes and medications interact to predict falls.

Bayesian classification of falls risk.

BACKGROUND: Prior research in falls risk prediction often relies on qualitative and/or clinical methods. There are two challenges with these methods. First, qualitative methods typically use falls history to determine falls risk. Second, clinical methods do not quantify the uncertainty in the classification decision. In this paper, we propose using Bayesian classification to predict falls risk using vectors of gait variables shown to contribute to falls risk. RESEARCH QUESTIONS: (1) Using a vector of risk ratios for specific gait variables shown to contribute to falls risk, how can older adults be classified as low or high falls risk? and (2) how can the uncertainty in the classifier decision be quantified when using a vector of gait variables? METHODS: Using a pressure sensitive walkway, biomechanical measurements of gait were collected from 854 adults over the age of 65. In our method, we first determine low and high falls risk labels for vectors of risk ratios using the k-means algorithm. Next, the posterior probability of low or high falls risk class membership is obtained from a two component Gaussian mixture model (GMM) of gait vectors, which enables risk assessment directly from the underlying biomechanics. We classify the gait vectors using a threshold based on Youden's J statistic. RESULTS: Through a Monte Carlo simulation and an analysis of the receiver operating characteristic (ROC), we demonstrate that our Bayesian classifier, when compared to the k-means falls risk labels, achieves an accuracy greater than 96% at predicting low or high falls risk. SIGNIFICANCE: Our analysis indicates that our approach based on a Bayesian framework and an individual's underlying biomechanics can predict falls risk while quantifying uncertainty in the classification decision.

Lower body predictors of glenohumeral compressive force in high school baseball pitchers.

The purpose of this study was to better understand how lower body kinematics relate to peak glenohumeral compressive force and develop a regression model accounting for variability in peak glenohumeral compressive force. Data were collected for 34 pitchers. Average peak glenohumeral compressive force was 1.72% ± 33% body weight (1334.9 N ± 257.5). Correlation coefficients revealed 5 kinematic variables correlated to peak glenohumeral compressive force (P < .01, α = .025). Regression models indicated 78.5% of the variance in peak glenohumeral compressive force (R2 = .785, P < .01) was explained by stride length, lateral pelvis flexion at maximum external rotation, and axial pelvis rotation velocity at release. These results indicate peak glenohumeral compressive force increases with a combination of decreased stride length, increased pelvic tilt at maximum external rotation toward the throwing arm side, and increased pelvis axial rotation velocity at release. Thus, it may be possible to decrease peak glenohumeral compressive force by optimizing the movements of the lower body while pitching. Focus should be on both training and conditioning the lower extremity in an effort to increase stride length, increase pelvis tilt toward the glove hand side at maximum external rotation, and decrease pelvis axial rotation at release.

Comparison of pitching kinematics between youth and adult baseball pitchers: a meta-analytic approach.

Coaches teach proper mechanics at a young age in an effort to increase pitching efficiency (i.e., proper pitching mechanics). Unfortunately, the mechanics taught to beginning pitchers are based on the findings from adult pitchers and may result in techniques that are detrimental to younger pitchers. The purpose of this study was to compare kinematics published for pitchers across various ages in an effort to determine whether the pitching techniques vary across developmental periods. A meta-analysis of papers published describing pitching kinematics for youth and adult pitchers was conducted. Maximal rotational velocity of the trunk and maximum external rotation of the shoulder were observed during the arm cocking phase. Peak magnitudes for abduction, horizontal adduction, and shoulder internal rotation were observed during the deceleration phase of the movement. In addition, by comparing previously published data across youth and adult pitchers, valuable insight into the differences in mechanics was gained. The results demonstrated that there are some distinct differences between youth and adult pitching mechanics. This finding may allow increased focus to be applied to those parameters observed to differ across age, increasing the knowledge base available for coaches to properly instruct youth pitchers.

Shoulder kinematics during pitching: comparing the slide step and traditional stretch deliveries.

Although studies have investigated the traditional stretch delivery, there is little biomechanical data describing the slide step delivery in baseball pitchers. Thus, the purpose of this study was to compare shoulder kinematics across the traditional stretch and slide step deliveries. To collect kinematic data from thirty-seven high school baseball pitchers, electromagnetic sensors recording at 140 Hz were affixed to various body segments. The average of those data from the three fastest pitches passing through the strike-zone were analyzed for each delivery. At the instances of front foot contact and ball release, no differences were observed between the two deliveries. At the instant of maximum shoulder external rotation, differences were observed between the two deliveries with regard to plane of elevation (t(72)=4.19, p<.001), elevation (t(72)=-3.38, p<.001), and axial rotation (t(72)=2.49, p=.015). The mechanical differences observed between the two delivery styles may have the potential to impact both performance and injury. Also, based on these results there may be a tradeoff between injury risk and performance. Thus, further study is warranted in an effort to identify the interrelationships between injury risk, performance, and pitching kinematics when throwing from the stretch position.

A biomechanical model correlating shoulder kinetics to pain in young baseball pitchers.

Previous work has postulated that shoulder pain may be associated with increases in both peak shoulder anterior force and peak shoulder proximal force. Unfortunately these relationships have yet to be quantified. Thus, the purpose of this study was to associate these kinetic values with reported shoulder pain in youth baseball pitchers. Nineteen healthy baseball pitchers participated in this study. Segment based reference systems and established calculations were utilized to identify peak shoulder anterior force and peak shoulder proximal force. A medical history questionnaire was utilized to identify shoulder pain. Following collection of these data, the strength of the relationships between both peak shoulder anterior force and peak shoulder proximal force and shoulder pain were analyzed. Although peak anterior force was not significantly correlated to shoulder pain, peak proximal force was. These results lead to the development of a single variable logistic regression model able to accurately predict 84.2% of all cases and 71.4% of shoulder pain cases. This model indicated that for every 1 N increase in peak proximal force, there was a corresponding 4.6% increase in the likelihood of shoulder pain. The magnitude of peak proximal force is both correlated to reported shoulder pain and capable of being used to accurately predict the likelihood of experiencing shoulder pain. It appears that those pitchers exhibiting high magnitudes of peak proximal force are significantly more likely to report experiencing shoulder pain than those who generate lower magnitudes of peak proximal force.

Predicting asymmetrical lower extremity strength deficits in college-aged men and women using common horizontal and vertical power field tests: a possible screening mechanism.

Strength deficits in the quadriceps and hamstrings have been linked to several lower extremity injuries. The most common protocol used in testing for these deficits is isokinetic strength testing, which is both costly and time consuming. Therefore, the purpose of this study was to employ common vertical and horizontal power field tests to identify those protocols that best predict lower extremity strength deficits. Data describing 22 healthy collegiate graduate students' vertical and horizontal power were collected using standard field tests (i.e., 2 feet vertical jump, single leg vertical jump, 40-, 50-, and 60-yd runs). In addition, data describing each subject's lower extremity strength deficits were collected by using the Biodex 840-000 Multi Joint System Isokinetic Dynamometer (Biodex Medical Systems, Shirley, NY, USA) set to report peak torque at 60° · s of flexion and extension and 180° · s of flexion and extension. Regression analyses indicated that 3 of the 4 strength deficit parameters could be predicted from a linear combination of field test results (p < 0.05). Of the strength deficits measured, hamstring deficits at flexion velocities of both 60° · s and quadriceps strength deficits at 60° · s were those that could be predicted using field test results. The results of this study, by increasing the diagnostic power of the clinician, may make it easier to develop strength training protocols designed specifically to target weak musculature in the lower extremity. This targeting of specific musculature, in an effort to return symmetrical strength to the lower extremity, may ultimately decrease the likelihood of lower extremity injury in college-aged men and women.

Muscle activation patterns of the upper and lower extremity during the windmill softball pitch.

Fast-pitch softball has become an increasingly popular sport for female athletes. There has been little research examining the windmill softball pitch in the literature. The purpose of this study was to describe the muscle activation patterns of 3 upper extremity muscles (biceps, triceps, and rhomboids [scapular stabilizers]) and 2 lower extremity muscles (gluteus maximus and medius) during the 5 phases of the windmill softball pitch. Data describing muscle activation were collected on 7 postpubescent softball pitchers (age 17.7 ± 2.6 years; height 169 ± 5.4 cm; mass 69.1 ± 5.4 kg). Surface electromyographic data were collected using a Myopac Jr 10-channel amplifier (RUN Technologies Scientific Systems, Laguna Hills, CA, USA) synchronized with The MotionMonitor™ motion capture system (Innovative Sports Training Inc, Chicago IL, USA) and presented as a percent of maximum voluntary isometric contraction. Gluteus maximus activity reached (196.3% maximum voluntary isometric contraction [MVIC]), whereas gluteus medius activity was consistent during the single leg support of phase 3 (101.2% MVIC). Biceps brachii activity was greatest during phase 4 of the pitching motion. Triceps brachii activation was consistently >150% MVIC throughout the entire pitching motion, whereas the scapular stabilizers were most active during phase 2 (170.1% MVIC). The results of this study indicate the extent to which muscles are activated during the windmill softball pitch, and this knowledge can lead to the development of proper preventative and rehabilitative muscle strengthening programs. In addition, clinicians will be able to incorporate strengthening exercises that mimic the timing of maximal muscle activation most used during the windmill pitching phases.

Pelvis and torso kinematics and their relationship to shoulder kinematics in high-school baseball pitchers.

It was the purpose of our study to examine the kinematics of the pelvis and torso and determine their relationship to the kinematics of the shoulder in high-school baseball pitchers. A single group, repeated-measures design was used to collect pelvis, torso, and shoulder kinematics throughout the pitching motion. Subjects threw a series of maximal effort fastballs to a catcher located the regulation distance (18.44m) from the pitching mound, and those data from the fastest pitch passing through the strike zone were analyzed. After test trials, kinematic data were analyzed using a series of descriptive statistics to identify outliers and determine the nature of the distribution before testing for the presence of relationships between the various parameters. Results indicated that for several parameters, the actions at and about the shoulder are strongly related to the actions of the pelvis and torso throughout the pitching motion. However, although pelvis and torso kinematics throughout the pitching motion were inversely related to both shoulder elevation and the plane of shoulder elevation, only the rate of axial torso rotation was significantly related to these shoulder parameters. More importantly, the rate of axial torso rotation is significantly related to these shoulder parameters in a way that may help explain the high rate of shoulder injury in high-school pitchers. Therefore, strength training should focus on developing a strong stable core including the gluteal musculature in an attempt to control the rate of torso rotation during the pitch.

Gluteal muscle group activation and its relationship with pelvis and torso kinematics in high-school baseball pitchers.

The purpose of this study was to examine the activation patterns of the gluteal muscle group and their relationship to pelvis and torso kinematics throughout the high-school pitching motion. A single group, repeated-measures design was used to collect gluteus maximus and gluteus medius muscle activity through surface electromyography for the preferred and nonpreferred sides during the various phases of the pitching motion. In addition, data describing the kinematics of the pelvis and torso were collected at foot contact, maximum shoulder external rotation, ball release, and maximum shoulder internal rotation. For all pitchers, preferred gluteus maximus activity was observed to be in excess of 100% of their maximum voluntary isometric contraction throughout the stride and arm-cocking phases of the pitching motion. The observed means for the preferred gluteus medius, nonpreferred gluteus maximus, and nonpreferred gluteus medius, although different in magnitude, were similar in pattern. From the conclusion of the stride phase, through the conclusion of the arm-cocking phase, muscle activity increased for all pitchers. In examining the relationship between the rate of axial pelvis rotation and gluteal activity, several significant relationships were observed. In contrast, no significant relationships were observed with gluteal activity parameters and the rate of axial torso rotation. However, because the pitching motion progresses sequentially from the pelvis to the torso, variability in pelvis rotation may be directly related to variability in torso rotation. The findings from this study indicate that during the baseball pitch, there is a need for greater control of gluteal activation throughout the pitching motion.

Biomechanical analysis of forearm pronation and its relationship to ball movement for the two-seam and four-seam fastball pitches.

This study examined forearm pronation in relation to both the vertical and horizontal ball movement measured for 2 variations of the fastball pitch. Ten healthy collegiate baseball pitchers participated in the study (age: 19.4 +/- 0.7 yr, height: 1.90 +/- 0.06 m, mass: 88.50 +/- 9.05 kg). Reflective markers were placed at the level of each joint center's location, and standard high-speed video techniques were used to record the participants as they threw 10 maximal effort fastball pitches. Marker positions were digitized in each video frame from which forearm pronation data were calculated. Across all pitchers, magnitude of both the vertical and horizontal ball movement was observed to be greater for the 2-seam fastball than for the 4-seam fastball. Regardless of pitch type, positive relationships were observed between all forearm pronation parameters and both vertical and horizontal ball movement. A significant positive correlation (r = 0.583, p < 0.01) was identified between forearm pronation acceleration at ball release and the magnitude of vertical ball movement regardless of pitch type. These results suggest that pitchers may be able to manipulate the magnitude of vertical ball movement by altering pronation accelerations at ball release. In addition, it appears that pitchers should alter their current training techniques so as to increase the endurance capabilities of the primary pronator muscles of the forearm. In doing so, they may be able to limit the effects of fatigue on these muscles during pitching, thus preventing a decrease in the magnitude of vertical ball movement that typically occurs late in a pitching performance.

Anterior shoulder forces in professional and Little League pitchers.

BACKGROUND: The developing musculoskeletal system of a youth pitcher is substantially different from that of the adult professional pitcher, predisposing the younger players to a different set of injuries. METHODS: High-speed videography of 39 professional and 13 youth pitchers were obtained. High-speed motion analysis was performed to calculate average anterior forces and arm positions at maximal force generation. RESULTS: Professional players generated an average of 33.8+/-14.4 N/kg maximal anterior force, corresponding to 151.9+/-17.0 degrees of external rotation. Youth pitchers generated 16.2+/-3.8 N/kg of anterior forces, corresponding to 118.0+/-23.4 degrees of external rotation. The degree of coronal abduction and horizontal abduction between the 2 groups were not significantly different-92.4+/-9.0 degrees in professionals versus 91.7+/-7.9 degrees in the youth and 11.1+/-11.1 degrees of horizontal abduction in professionals versus 7.8+/-14.1 degrees in the younger throwers. Professional pitchers exerted higher internal rotation torque at 19.4+/-4.1 Nm/kg versus 5.6+/-1.0 Nm/kg in youth, and compressive forces were found to be 121.7+/-21.7 N/kg in professional pitchers compared with 47.5+/-7.6 N/kg in the youth pitchers. CONCLUSIONS: Youth pitchers experience significant anterior shoulder forces and internal rotation torques, although these are lower than professional pitchers. CLINICAL RELEVANCE: Overhead throwing as a youth can lead to shoulder injuries and can predispose the shoulder to more significant injuries as an adult pitcher.

A biomechanical analysis of youth pitching mechanics.

BACKGROUND: It is estimated that nearly 6% of youth baseball participants seek medical attention for injuries sustained during play. Most injuries are overuse injuries, and 26% are to the shoulder or upper arm. By quantifying youth pitching biomechanics, knowledge can be gained concerning the manner in which these injuries are sustained during play. METHODS: Sixteen healthy right hand-dominant baseball pitchers participated in this study. After digitization of 21 bony landmarks, kinematic calculations were conducted using the 3-dimensional coordinates from each video frame. Data were time normalized, forcing major temporal components of the movement to occur at specific intervals. Segment-based reference frames were established, and resultant joint kinetics were projected onto each reference frame. Kinetic data were normalized and calculated along or about the anterior/posterior, medial/lateral, and proximal/distal axes. RESULTS: Maximum trunk rotation and external shoulder rotation were observed during arm cocking. Each of the remaining kinematic parameters peaked after ball release. All maximum values for joint kinetics were measured during arm cocking with the exception of compressive forces experienced at the shoulder and elbow, which peaked after the instant of ball release. CONCLUSIONS: Data produced in this study indicate that youth pitchers initiate trunk rotation early in the movement, which can lead to shoulder hyperangulation. Opposing torques at each end of the humerus also produce a large net torque about the longitudinal axis of the humerus during late arm cocking and may increase humeral retrotorsion in youth pitchers. Underdeveloped musculature in the rotator cuff may lead to difficulty controlling throwing-arm deceleration, causing an increase in horizontal adduction across the torso. CLINICAL RELEVANCE: An improved understanding of youth pitching mechanics is gained from the data collected, analyzed, and discussed in this study. Through increases in the knowledge pertaining specifically to the mechanics of youth pitchers, the opportunity to develop pitching mechanics specifically designed for preventing injuries in little league pitchers arises. LEVEL OF EVIDENCE: This study is a Level 4 study describing youth pitching biomechanics and how they relate to possible injuries.