Impact of debulking therapy on the clinical outcomes of axicabtagene ciloleucel in the treatment of relapsed or refractory large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2. Among the 50 patients in Cohort 5 who received axi-cel, 40% received ≥3 prior lines of chemotherapy, and 40% had disease that progressed while on the most recent chemotherapy. Forty-eight patients (96%) received debulking therapy, 14 (28%) radiotherapy only, and 34 (71%) systemic immunochemotherapy. Median decrease in tumor burden (per sum of product of diameters of target lesions) relative to screening was 17.4% with R-ICE/R-GDP, 4.3% with other debulking chemotherapies, and 6.3% with radiotherapy only. All patients were followed for ≥8 months. CRS was reported in 43 patients (86%), with 1 patient (2%) experiencing grade ≥3. NEs were reported in 28 patients (56%), with 6 (12%) experiencing grade ≥3. Cytopenias were the most frequent grade ≥3 adverse event (AE); 19 (38%) and 18 (36%) treated patients had any and grade ≥3 prolonged thrombocytopenia, respectively, and 25 (50%) and 24 (48%) patients had any and grade ≥3 prolonged neutropenia, respectively. Overall, patients who received debulking chemotherapy had higher incidences of serious treatment-emergent AEs than those who received radiotherapy only. At the 24-month analysis, objective response rate was 72%, and complete response rate was 56%. Median duration of response, progression-free survival, and overall survival were 25.8, 3.1, and 20.6 months, respectively. These results from exploratory Cohort 5 demonstrate the feasibility of debulking prior to axi-cel, and together with current real-world evidence, suggest that debulking regimens may help minimize the frequency and severity of CRS and NEs in patients with R/R LBCL. The incidence of other AEs observed in Cohort 5 suggest the risk/benefit profile was not improved via the debulking regimens studied here.

Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume.

ABSTRACT: Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response). All P values are descriptive. Within high- and low-MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care. EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel and was significantly shorter with standard care. PFS was shorter in patients with high MTV vs low MTV in both the axi-cel and standard-care arms, and median MTV was lower in patients in ongoing response at data cutoff vs others. Median MTV was higher in patients treated with axi-cel who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively. Baseline MTV less than or equal to median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

Comparisons and Intercorrelations of Physical Performance Variables of Operational Preparedness in Special Operations Forces.

INTRODUCTION: Marine Forces Special Operations Command (MARSOC) deploys teams of operators (OP) and enablers (EN) to accomplish special operations missions. OP and EN are required to train and deploy together to accomplish these missions; however, they have different training and selection pipelines. Advanced strength and conditioning training strategies are applied to both OP and EN to enhance physical preparedness; however, it is unclear how the selection pipeline of these two personnel types affects overall physical preparedness and the relationships between performance variables. The purpose of this study is to gain a greater understanding of the relationships of a wide array of physical preparedness variables in OP and EN in an effort to streamline testing and training strategies. MATERIALS AND METHODS: For this study, 155 male (82 OP, 73 EN) MARSOC personnel (age: 29.5 ± 4.9 years, mass: 87.9 ± 11.1 kg, height: 1.79 ± 0.07 m) completed a physical preparedness assessment that included a DEXA assessment of body composition (BF%), 27.4 m sprint (30 yd), countermovement jump (VJ), 5-10-5 pro-agility (Agility), medicine ball toss (UBP), isometric mid-thigh pull (IMTP), and a 30 second (AnC) and 5 minute (AC) non-motorized treadmill run. Independent samples t tests, Mann-Whitney U tests, and Spearman's Rank correlations were used to compare variables between OP and EN. RESULTS: OP demonstrated greater VJ, UBP, IMTP, AnC, and AC (P < 0.05); and significantly lower BF% and agility time (P < 0.05). Measurements of mass, height, body mass index, and 30 yd were not significantly different (P > 0.05). Weak to moderate correlations were seen between anthropometric and performance variables. OP and EN demonstrated similar correlations for most performance and anthropometric variables. CONCLUSIONS: These results suggest that MARSOC OP demonstrate better physical preparedness over EN, while similar trends are observed between performance variables. Tests with moderate to high correlations may be removed from the protocol to account for testing time constraints. Height, weight, and BF% variables are poorly correlated with performance, particularly in OP, questioning their value in physical performance assessments in this population.

Training Strategies Maintain Performance Characteristics in Marines Selected for Marine Forces Special Operations Individualized Training Course.

INTRODUCTION: Marines must complete an intensive Assessment and Selection (A&S) course before becoming a U.S. Marine Forces Special Operations Command (MARSOC) Raider. Following selection, marines are given training recommendations designed to maintain performance characteristics deemed relevant to successfully complete a rigorous 9-month Individualized Training Course (ITC). However, training strategies are individually implemented by the marine, and the time between the two courses is highly irregular, ranging between 2 months and 24 months based on operational factors related to military occupational specialty (MOS). The purpose of this study was to evaluate changes in performance between the completion of A&S and the start of ITC and to examine if the duration between courses and previous MOS influenced changes in performance. MATERIALS AND METHODS: Body fat percentage (BF%), anaerobic power (AP), anaerobic capacity (AC), aerobic capacity (VO2max), knee flexion (KF), knee extension (KE), trunk extension (TE), and trunk flexion (TF) isokinetic strength were collected on 38 marines (age: 25.1 ± 2.7 years, height: 1.77 ± 0.05 m, mass: 83.2 ± 7.7 kg, Post-A&S to ITC start: 204.1 ± 68.4 days) following A&S and directly before ITC. RESULTS: Pre-ITC students had significantly greater mass (P = .002), BF% (P = .000), and AP (P = .039). There were no significant changes in AC (P = .170), VO2max (P = .259), KF (P = .400), KE (P = .320), TE (P = .178), and TF (P = .643). There was no significant relationship between performance outcomes and time between courses and previous MOS. CONCLUSION: Current training strategies appear effective at addressing performance deficits that occur as a result of A&S, while maintaining high levels of KF, KE, TE, TF, AC, and VO2max. However, pre-ITC students still exhibited AP deficits compared to active marine raiders, so forthcoming programming may benefit from an increased emphasis on AP. Assessment of additional selectees at these timepoints, as well as students before A&S may provide valuable information to MARSOC human performance specialists to develop programing, ultimately leading to a higher ITC graduation rate, increased force readiness, and decreased financial burden forcewide.

Neurocognitive function influences dynamic postural stability strategies in healthy collegiate athletes.

OBJECTIVES: Poorer neurocognitive performance may increase lower extremity injury risk due to alterations in biomechanics. However, it is unclear if poorer neurocognitive function may be associated with altered dynamic postural stability. Therefore, the purpose of this study was to investigate the relationship between neurocognitive performance and dynamic postural stability in healthy collegiate athletes. DESIGN: Cross-sectional cohort. METHODS: Forty-five Division-I collegiate athletes (21 males, 24 females; age: 19.69 ±â€¯1.50) completed neurocognitive assessments from the NIH Toolbox® (NIHTB). Three groups were established from the NIHTB composite score: high performers (HP), moderate performers (MP), and low performers (LP). Additionally, participants completed a dynamic hop-to-stabilization task. Accelerometer and gyroscopic data were recorded during landing through an inertial measurement unit (IMU) on the participant's low back. The root mean squared (RMS) of the accelerometer and gyroscope was calculated for the orthogonal planes and the resultant vector. Group differences for demographic variables, NIHTB composite scores, and IMU based measures were analyzed with one-way ANOVAs with Bonferroni post hoc analyses were performed. Cohen's d effect sizes were also calculated. RESULTS: Post hoc tests determined the LP group had higher vertical acceleration RMS values (p = 0.013, d = -0.85) and lower anteroposterior acceleration RMS values (p = 0.005, d = 0.95) compared to the HP group. CONCLUSIONS: Neurocognitive performance may influence dynamic postural stability strategies in athletes. Higher neurocognitive performers may use different approaches to perform difficult postural tasks by adopting strategies associated with lower vertical and higher anteroposterior acceleration compared to lower neurocognitive performers.

Asymmetrical Loading Patterns in Military Personnel With a History of Self-Reported Low Back Pain.

BACKGROUND: Servicemembers are required to operate at high levels despite experiencing common injuries such as chronic low back pain. Continuing high levels of activity while compensating for pain may increase the risk of musculoskeletal injuries. As such, the purpose of this project was to determine if servicemembers with chronic low back pain have reduced lower extremity performance, and if they use alternate strategies to complete a functional performance task as compared to healthy servicemembers. METHODS: Of a total of 46 male United States Marine Corps Forces Special Operations Command (MARSOC) personnel, 23 individuals who suffered from chronic low back pain (age = 28.6 ± 4.4 years, weight = 84.2 ± 6.8 kg) and 23 healthy controls (age = 27.9 ± 3.8 years, weight = 83.8 ± 7.7 kg) completed a stop jump task. In this task, three-dimensional biomechanics were measured, and lower extremity and trunk strength were assessed. RESULTS: The low back pain group exhibited higher vertical ground reaction force impulse on the dominant limb (0.26% body weight [BW]/s), compared to the nondominant limb (0.25% BW/s, p = .036). The control group demonstrated relationships between jump height and strength in both limbs (dominant: r = 0.436, p = .043; nondominant: r = 0.571, p = .006), whereas the low back pain group demonstrated relationships between jump height and dominant limb knee work (r = 0.470, p = .027) and ankle work (r = 0.447, p = .037). CONCLUSIONS: This study demonstrates that active-duty MARSOC personnel with a history of low back pain reach similar levels of jump height during a counter movement jump, as compared to those without a history of low back pain. However, the asymmetries displayed by the low back pain group suggest an alternate strategy to reaching similar jump heights as compared to healthy individuals.

Altered Physical Performance Following Advanced Special Operations Tactical Training.

ABSTRACT: Winters, JD, Heebner, NR, Johnson, AK, Poploski, KM, Royer, SD, Nagai, T, Randall, CA, Abt, JP, and Lephart, SM. Altered physical performance following advanced special operations tactical training. J Strength Cond Res 35(7): 1809-1816, 2021-The purpose of this study was to determine how the unique challenges of specific military tactical training phases influence overall physical performance characteristics. Broad jump, 5-10-5, 300-yd shuttle, percent body fat (%BF), anaerobic power (AP) and anaerobic capacity (AC), maximal oxygen uptake (V̇o2max), isokinetic knee extension/flexion strength, shoulder internal/external rotation strength, and trunk extension/flexion strength were collected on 73 United States Marine Corps Forces Special Operations Command (MARSOC) students (age: 27.4 ± 3.8 years, height: 178.7 ± 6.6 cm, and body mass: 85.8 ± 9.4 kg) at the beginning of (P1), in between (P2), and at the completion of 2 distinct tactical training phases (P3). Linear mixed models were used to analyze within-subject performance changes over the 3 time points, and post hoc Bonferroni pairwise comparisons analyzed performance changes between each testing time point. There were significant changes in broad jump (p < 0.0001), 5-10-5 agility time (p < 0.001), %BF (p = 0.011), AP (p < 0.0001), V̇o2max (p = 0.001), and both right and left shoulder internal rotation strength (p = 0.004 and p = 0.015, respectively) between P1 and P2. There were also significant changes in 300-yd shuttle run time (p = 0.001), AP (p < 0.0001), AC (p < 0.0001), left knee extension strength (p = 0.006), trunk flexion strength (p < 0.0001), and left shoulder external rotation strength (0.027) between P2 and P3. Identifying the effect that specific tactical training phases may have on physical performance will allow for the development of effective phase-specific evidence-based human performance programs, reducing performance deficits and thereby reducing the risk of injury.

INFLUENCE OF LIMB DOMINANCE AND SHOULDER INJURY ON STRENGTH AND EXPLOSIVE FORCE IN US MARINES.

BACKGROUND: The specialized roles of many military personnel require specific skills and high physical demands, placing unique stresses on the shoulders and increasing risk of injury. As normal dominant/nondominant shoulder asymmetries have been established in military personnel, bilateral strength comparisons must be understood in context of daily physical demands to monitor patients' progress or readiness to return to duty. PURPOSE: This study aims to assess bilateral differences in strength and explosive force in United States Marines with a history of dominant or nondominant shoulder pathology. STUDY DESIGN: Cross-Sectional. METHODS: A total of 52 full-duty, male US Marines with a shoulder injury within the prior year participated. Bilateral isokinetic shoulder internal (IR) and external (ER) rotation strength, and peak force (Peak Force) and average rate of force production (Avg Rate) during an explosive push-up were collected. Dominant versus nondominant side data were independently examined within each group (DOM: dominant injury, NOND: nondominant injury). Comparison between DOM and NOND, as well as previously published CON (no history of shoulder injury) was also completed. RESULTS: NOND (n = 26) demonstrated significantly less IR (p < 0.001) and ER (p = 0.003) strength and Peak Force (p = 0.001) and Avg Rate (p = 0.047) on the injured side, while DOM (n = 26) demonstrated no bilateral differences in strength or push-up performance. Comparison between the three groups showed that NOND demonstrated significantly less ER strength than CON (p = 0.022). CONCLUSIONS: Military personnel demonstrate asymmetric strength patterns likely due to increased demand of the dominant shoulder. US Marines with a history of injury to the nondominant shoulder performed differently than those with a dominant side injury, presenting with both strength and push-up asymmetries. They also demonstrated significant ER strength deficits compared to CON. Common clinical practice and previous literature often compare injured and uninjured limbs or injured individuals to healthy controls, but further distinction of dominant or nondominant side may provide more accurate information needed to develop targeted treatment strategies. CLINICAL RELEVANCE: Recognizing unique occupational demands and how patients may present differently with dominant versus nondominant side shoulder injuries are important considerations for ensuring accurate assessment and effective individualized rehabilitation. LEVEL OF EVIDENCE: 3.

Military Protein Intake Related to Strength and Fat Mass Independent of Energy Intake.

INTRODUCTION: Kinetic military units operate in austere training environments and deprivation not commonly experienced by competitive athletes. Nutritional strategies to protect against decrements in performance and potential injury risk may differ for these two groups. A cross sectional analysis was conducted to determine energy and macronutrient characteristics associated with performance metrics. MATERIALS AND METHODS: 78 male subjects (age: 28.4 ± 6.0 years, height: 178.3 ± 6.7 cm, mass: 84.3 ± 9.4 kg, 8.5 ± 5.8 years of service) assigned to Marine Corps Forces Special Operations Command completed a 1-day performance assessment. Body mass, lean body mass, fat mass (FM), aerobic capacity (VO2max), lactate inflection point (LT), anaerobic power, anaerobic capacity, knee flexion strength, knee extension strength, peak knee flexion strength, and peak knee extension strength outcome values were recorded. Dietary intake was collected using automated self-administered 24-hour dietary recall (ASA24). Performance assessment scores were compared with macronutrient intake and controlled for energy intake using analysis of covariance. RESULTS: Differences in knee flexion strength, knee extension strength, peak knee flexion strength, and peak knee extension strength were significant across low (LPRO), medium (MPRO), and high (HPRO) protein intake groups (p < 0.05) with LPRO performance metrics significantly lower than both MPRO and HPRO and MPRO significantly lower than HPRO. FM was significantly higher in LPRO than MPRO or HPRO (p < 0.05). Low carbohydrate intake (LCHO) was associated with greater body mass and FM compared with high (HCHO) (p < 0.05). There was no association between fat intake and any variable. CONCLUSIONS: Increases in protein intake may have beneficial performance effects independent of total energy intake, while moderate increases in carbohydrate intake may not be sufficient to enhance physical performance in a special operations population.

Older women's perceptions of wearable and smart home activity sensors.

Introduction: The aim of this study was to characterize perceptions of wearable and smart home technologies of older women using semi-structured interviews.Methods and Procedures: Participants (n = 10) were shown two wearable sensors and a smart home sensor. All participants were 60 years of age or older with the exception of one participant (ages: 57-70,average age: 64.6 years). Sensor function and placement were explained. Participants were asked questions about technology, perceptions of sensors, and thoughts about the use of these types of sensors. Interview transcripts were analyzed to identify themes related to technology acceptance, perceived usefulness, and privacy issues.Main Outcome and Results: Participants perceived wearable and smart home sensors as acceptable for personal activity data collection. In general, wearable sensors were perceived as more useful than smart home sensors because most participants had high levels of activities outside their homes. Participants had few concerns about data sharing. Privacy issues related to perceived risk for break-ins or unwanted disclosure of activity levels.Conclusion: Given the higher proportion of women over men in the older adult population, and some of the aging-related health risks that women face, it is important to understand older women's perceptions of different types of sensor technologies.

Simulated hip abductor strengthening reduces peak joint contact forces in patients with total hip arthroplasty.

Lower extremity muscle strength training is a focus of rehabilitation following total hip arthroplasty (THA). Strength of the hip abductor muscle group is a predictor of overall function following THA. The purpose of this study was to investigate the effects of hip abductor strengthening following rehabilitation on joint contact forces (JCFs) in the lower extremity and low back during a high demand step down task. Five THA patients performed lower extremity maximum isometric strength tests and a stair descent task. Patient-specific musculoskeletal models were created in OpenSim and maximum isometric strength parameters were scaled to reproduce measured pre-operative joint torques. A pre-operative forward dynamic simulation of each patient performing the stair descent was constructed using their corresponding patient-specific model to predict JCFs at the ankle, knee, hip, and low back. The hip abductor muscles were strengthened with clinically supported increases (0-30%) above pre-operative values in a probabilistic framework to predict the effects on peak JCFs (99% confidence bounds). Simulated hip abductor strengthening resulted in lower peak JCFs relative to pre-operative for all five patients at the hip (18.9-23.8 ±â€¯16.5%) and knee (20.5-23.8 ±â€¯11.2%). Four of the five patients had reductions at the ankle (7.1-8.5 ±â€¯11.3%) and low back (3.5-7.0 ±â€¯5.3%) with one patient demonstrating no change. The reduction in JCF at the hip joint and at joints other than the hip with hip abductor strengthening demonstrates the dynamic and mechanical interdependencies of the knee, hip and spine that can be targeted in early THA rehabilitation to improve overall patient function.

Patterns and Associations of Shoulder Motion, Strength, and Function in MARSOC Personnel Without History of Shoulder Injury.

Introduction: Military personnel are at an increased risk of shoulder injuries due to training and deployment demands, however, there is a lack of information on the tactical athlete's upper extremity profile. Therefore, the purpose of this study was to examine shoulder musculoskeletal characteristics, including range of motion (ROM), strength, and function, and the relationships between these measures in Marine Corps Forces Special Operations Command (MARSOC) personnel without history of shoulder injury. Materials and Methods: Participants included 195 full-duty male MARSOC personnel (age: 25.38 ± 2.85 yr; height: 1.79 ± 0.06 m, mass: 82.79 ± 7.88 kg) without history of shoulder injury. Measurements of ROM, strength, and function were obtained bilaterally. Shoulder internal rotation (IR) and external rotation (ER) ROM were summed to calculate total arc of motion (ARC). Shoulder IR and ER strength were assessed using an isokinetic dynamometer. Function was evaluated with an explosive push-up. Results: MARSOC personnel present with significantly increased ER ROM, and decreased IR ROM and ARC in their dominant shoulder. They demonstrated greater IR strength and peak force during the explosive push-up on the dominant side but no bilateral differences in average or peak rate were found. Correlation analyses suggest a weak inverse relationship between strength and ARC (r = -0.15 to -0.24). Positive relationships between strength and function were identified except for dominant IR strength and push-up variables. Those with the greatest ARC demonstrated significantly weaker IR and ER strength compared to those with less motion. Conclusions: MARSOC personnel demonstrate shoulder ROM and strength symmetry patterns similar to overhead athletes. Increased dominant shoulder strength does appear to translate to a bilateral functional performance, but overall performance may be limited by the weaker nondominant upper extremity. As ARC increases, IR and ER rotation strength decrease. Repetitive, increased loading of the dominant shoulder during functional movements and training may increase risk of chronic, overuse-type injuries, common to the military. Unilateral exercises and movement analysis should be incorporated to encourage proper development of bilateral shoulder strength, which may be particularly important in those with high ranges of ARC.

Physical, Physiological, and Dietary Comparisons Between Marine Corps Forces Special Operations Command Critical Skills Operators and Enablers.

Introduction: Tactical demands of a Marine Corps Forces Special Operations Command (MARSOC) Critical Skills Operator (CSO) require high levels of physical performance. During combat deployments, teams of CSOs are supplemented with enablers who specialize in mission-specific tasks. MARSOC CSOs and enablers serve alongside each other in extreme combat environments, often enduring the same physical demands, but the selection process for each group is very different. The purpose of this observational study was to quantify the physical, physiological, and dietary differences of MARSOC CSOs and enablers, as this may have a direct impact on tactical performance and provide important information to shape future research. Materials and Methods: Fat free mass (FFM), fat mass (FM), fat mass index (FMI), fat free mass index (FFMI), anaerobic power (AP), anaerobic capacity (AC), aerobic capacity (VO2max), knee flexion (KF), knee extension (KE), trunk extension (TE), and trunk flexion (TF) isokinetic strength were collected. Dietary intake was collected using automated self-administered 24-hr dietary recalls (ASA24) for a subgroup of subjects. Results: Testing on 164 male CSOs (age: 27.5 ± 3.8 yr, height: 178.7 ± 6.5 cm, mass: 85.7 ± 9.1 kg, and 7.6 ± 2.9 yr of military service) and 51 male enablers (age: 27.8 ± 5.4 yr, height: 178.4 ± 8.5 cm, mass: 83.8 ± 11.8 kg, and 7.9 ± 5.4 yr of military service) showed there were no significant differences for age, height, mass, or years of military service. (p > 0.05). CSOs demonstrated greater physiological performance in AP (W/kg) (p = 0.020), AC (W/kg) (p = 0.001), and VO2max (ml/kg/min) (p = 0.018). There were no significant differences in FM and FFM (p > 0.05), however CSOs demonstrated significantly higher FFMI (p = 0.011). CSOs also demonstrated greater KF (%BW) (p = 0.001), KE (%BW) (p = 0.001), TE (%BW) (p = 0.010), and TF (%BW) (p = 0.016). No differences in energy or macronutrient intake were observed in the subgroup. Conclusions: MARSOC CSOs demonstrated significantly greater FFMI, AP, AC, VO2max, KF, KE, TE, and TF compared with enablers. Dietary intake was consistent between groups, but fueling concerns were identified for all personnel in the subgroup. These findings suggest the need for future studies to examine what physiological and strength thresholds are necessary to operate effectively as a member of a MSOT and determine the relationship between specific performance deficits and risk of injury. In addition, the integration of nutrition strategies that augment and optimize the performance of both CSOs and enablers may be beneficial.

The impact of hip implant alignment on muscle and joint loading during dynamic activities.

BACKGROUND: Component alignment is an important consideration in total hip arthroplasty. The impact of changes in alignment on muscle forces and joint contact forces during dynamic tasks are not well understood, and have the potential to influence surgical decision making. The objectives of this study were to assess the impact of femoral head/stem and cup component placement on hip muscle and joint contact forces during tasks of daily living and to identify which alignment parameters have the greatest impact on joint loading. METHODS: Using a series of strength-calibrated, subject-specific musculoskeletal models of patients performing gait, sit-to-stand and step down tasks, component alignments were perturbed and joint contact and muscle forces evaluated. FINDINGS: Based on the range of alignments reported clinically, variation in head/stem anteversion-retroversion had the largest impact of any degree of freedom throughout all three tasks; average contact forces 413.5 (319.1) N during gait, 262.7 (256.4) N during sit to stand, and 572.7 (228.1) N during the step down task. The sensitivity of contact force to anteversion-retroversion of the head/stem was 31.5 N/° for gait, which was similar in magnitude to anterior-posterior position of the cup (34.6 N/m for gait). Additionally, superior-inferior cup alignment resulted in 16.4 (4.9)° of variation in the direction of the hip joint contact force across the three tasks, with the most inferior cup placements moving the force vector towards the cup equator at the point of peak joint contact force. INTERPRETATION: A quantitative understanding of the impact and potential tradeoffs when altering component alignment is valuable in supporting surgical decision making.

Performance on a Clinical Quadriceps Activation Battery Is Related to a Laboratory Measure of Activation and Recovery After Total Knee Arthroplasty.

OBJECTIVE: To determine the relation between performance on a clinical quadriceps activation battery with (1) activation measured by doublet interpolation and (2) recovery of quadriceps strength and functional performance after total knee arthroplasty (TKA). DESIGN: Planned secondary analysis of a randomized controlled trial. SETTING: University research laboratory. PARTICIPANTS: Patients (N=162; mean age, 63±7y; 89 women) undergoing TKA. MAIN OUTCOME MEASURES: Patients were classified as high (quadriceps activation battery ≥4/6) or low (quadriceps activation battery ≤3/6) based on performance on the quadriceps activation battery measured 4 days after TKA. Differences between groups in activation and recovery at 1, 2, 3, 6, and 12 months after TKA were compared using a repeated-measures maximum likelihood model. RESULTS: The low quadriceps activation battery group demonstrated poorer quadriceps activation via doublet interpolation (P=.01), greater quadriceps strength loss (P=.01), and greater functional performance decline (all P<.001) at 1 month after TKA compared with the high quadriceps activation battery group. Differences between low and high quadriceps activation battery groups on all measures did not persist at 3 and 12 months (all P>.05). CONCLUSIONS: Poor performance on the quadriceps activation battery early after TKA is related to poor quadriceps activation and poor recovery in the early postoperative period. Patients in the low quadriceps activation battery group took 3 months to recover to the same level as the high quadriceps activation battery group. The quadriceps activation battery may be useful in identifying individuals who need specific interventions to target activation deficits or different care pathways in the early postoperative period to speed recovery after TKA.

Effects of neuromuscular reeducation on hip mechanics and functional performance in patients after total hip arthroplasty: A case series.

BACKGROUND: Following total hip arthroplasty, patients demonstrate compensatory movement strategies during activities of daily living such as walking and stair climbing. Movement compensations are important markers of functional decline in older adults and are related to poor functional capacity. Despite increased utilization of hip arthroplasty, persistent movement compensation, and functional performance deficits, no consensus on postoperative rehabilitation exists. Neuromuscular reeducation techniques offer a strategy to improve movement quality by emphasizing hip abductor performance and pelvic stability. This case series illustrates changes in movement strategy around the hip in response to targeted neuromuscular reeducation techniques after hip arthroplasty. METHODS: Five participants received an 8-week exercise program following total hip arthroplasty, emphasizing targeted neuromuscular reeducation techniques hallmarked by specific, weight-bearing exercise to improve hip abductor performance and pelvic stability. Five additional participants were supervised and followed for comparison. FINDINGS: Participants in the neuromuscular reeducation program improved their internal hip abductor moments and vertical ground reaction forces during walking and stair climbing. They also improved their functional performance and hip abductor strength outcomes. INTERPRETATION: Targeted neuromuscular reeducation techniques after total hip arthroplasty provided a positive effect on biomechanical outcomes, functional performance, and muscle strength. Through focused use of the hip abductor muscles, increased internal hip abductor moments were observed. This intervention potentially promotes pelvic stability, and may contribute to improved performance on tasks such as stair climbing, fast walking, and balance. The results suggest that neuromuscular reeducation offers a unique effect on movement strategy and function for patients following total hip arthroplasty.

Preliminary investigation of rate of torque development deficits following total knee arthroplasty.

BACKGROUND: To assess changes in maximal strength and rate of torque development (RTD) following TKA, and examine the relationships between these measures and physical function. METHODS: Thirty-five TKA patients and 23 controls completed isometric knee extensor torque testing preoperatively, 1, and 6 months after surgery. Maximal strength was calculated as the peak torque during a maximal voluntary isometric contraction (MVIC) of the knee extensor muscles, peak RTD (RTD(peak)) was calculated as the maximum value from the 1st derivative of the isometric knee extension torque data, RTD(25%) and RTD(50%) were calculated as the change in force over the change in time from force onset to 25% and 50% MVIC. Physical function was measured using a timed-up-and-go (TUG) and stair climbing test (SCT). RESULTS: RTD was significantly lower in the TKA group, at all-time points, compared to the Controls. MVIC and RTD significantly decreased 1-month following surgery (p=0.000 for all measures). RTD(peak) measures added to linear regressions with strength improved the prediction of TUG scores (p=0.006) and the SCT scores (p=0.015) 1-month post-surgery. Adding RTD(50%) to the regression model, following MVIC, improved predicting both TUG (p=0.033) and SCT (p=0.024). At 6-months, the addition of RTD(25%) to the regression model, following MVIC, improved the prediction of TUG (p=0.037) and SCT (p=0.036). CONCLUSION: Following TKA, physical function is influenced by both the maximal strength and the rate of torque development of the knee extensors, and the prediction of function is improved with the addition of RTD compared to that of maximal strength alone.

Quadriceps rate of force development affects gait and function in people with knee osteoarthritis.

OBJECTIVE: Quadriceps weakness exists in people with knee osteoarthritis (OA), but other muscle factors like rate of force development (RFD) may also be affected by knee OA. The purpose of this study was to determine if people with knee OA have deficits in quadriceps RFD, determine if quadriceps RFD would improve predicting knee joint power absorption and generation during free and fast walking, and determine if RFD would improve predicting functional outcomes. METHODS: 26 subjects with knee OA and 23 healthy control subjects performed maximal voluntary isometric strength (MVIC) and RFD measures of the quadriceps. Subjects also underwent a 3-D motion analysis of both self-selected free and self-selected fast walking speeds. Joint kinetics were calculated from inverse dynamics. RESULTS: RFD was not different by group (p = 0.763), however, the OA subjects generated the highest peak RFD at a lower % MVIC (p = 0.008). Controls walked significantly faster at both free and fast walking speeds (p = 0.001, p = 0.029). Knee angles at heel strike and peak knee extension were lower (p = 0.004, p = 0.027) in the OA group. During fast walking knee power generation was higher in controls (p = 0.028). MVIC and force of highest peak RFD predicted KOOS-ADL score in the OA subjects, but only MVIC predicted stair climbing time. CONCLUSIONS: The submaximal force at which peak RFD occurs plays a significant role in knee joint power as well as functional measures in the OA subjects, providing further evidence that factors other than maximal strength are also important in people with knee OA.

Effects of statins on skeletal muscle: a perspective for physical therapists.

Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.

Age-related mechanical work expenditure during normal walking: the Baltimore Longitudinal Study of Aging.

The aim of this cross-sectional study was to delineate age-associated kinematic and kinetic gait patterns of normal walking, and to test the hypothesis that older adults exhibit gait patterns that reduce generative mechanical work expenditures (MWEs). We studied 52 adult Baltimore Longitudinal Study of Aging participants (means age 72+/-9, from 60 to 92 years) who could walk 4m unaided. Three-dimensional kinematic and kinetic parameters assessed during rotation-defined gait periods were used to estimate MWEs for the rotation of lower extremities about the medial-lateral (ML) and anterior-posterior (AP) axes of proximal joints, which represent MWEs in the AP and ML sides, respectively. Relationships between gait parameters and age were examined using regression analysis with adjustments for walking speed, sex, height, and weight. Older age was associated with slower self-selected walking speed (p<0.001), shorter stride length (p<0.001), and greater propensity of landing flat-footed (p=0.003). With older age, hip generative MWE for thigh rotation was lower about the AP axis (hip abduction and adduction) during stance (p=0.010) and higher about the ML axis (hip extension and flexion) during late stance (p<0.001). Knee absorptive MWE for shank rotation about the AP axis (knee abduction and adduction) during early stance was also lower with older age (p<0.003). These age-related gait patterns may represent a compensatory effort to maintain balance and may also reflect mobility limitations.