Association of homozygous variants of STING1 with outcome in human cervical cancer.

DNA-sensing receptor Cyclic GMP-AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS-STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING-encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy. To start to address this, we defined the genetic landscapes of STING1 in cervical scrapings and investigated their corresponding clinical characteristics across a unique cohort of cervical cancer patients and compared them with independent control cohorts. Although we did not observe an enrichment of particular STING1 allelic variants in cervical cancer patients, we did find that the occurrence of homozygous variants HAQ/HAQ and R232H/R232H of STING1 were associated with both younger age of diagnosis and higher recurrence rate. These findings were accompanied by worse survival, despite comparable mRNA and protein levels of STING and numbers of infiltrated CD8+ T cells. Our findings suggest that patients with HAQ/HAQ and R232H/R232H genotypes may have a dysfunctional cGAS-STING pathway that fails to promote efficient anticancer immunity. Interestingly, the occurrence of these genotypes coincided with homozygous presence of the V48V variant, which was found to be individually associated with worse outcome. Therefore, we propose V48V to be further evaluated as a novel prognostic marker for cervical cancer.

Multicenter Comparison of Molecular Tumor Boards in The Netherlands: Definition, Composition, Methods, and Targeted Therapy Recommendations.

BACKGROUND: Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. MATERIALS AND METHODS: MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. RESULTS: Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). CONCLUSION: MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. IMPLICATIONS FOR PRACTICE: Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing.

The Added Value of Musculoskeletal Simulation for the Study of Physical Performance in Military Tasks.

The performance of military tasks is often exacerbated by additional load carriage, leading to increased physical demand. Previous studies showed that load carriage may lead to increased risk of developing musculoskeletal injuries, a reduction in task speed and mobility, and overall performance degradation. However, these studies were limited to a non-ambulatory setting, and the underlying causes of performance degradation remain unclear. To obtain insights into the underlying mechanisms of reduced physical performance during load-carrying military activities, this study proposes a combination of IMUs and musculoskeletal modeling. Motion data of military subjects was captured using an Xsens suit during the performance of an agility run under three different load-carrying conditions (no load, 16 kg, and 31 kg). The physical performance of one subject was assessed by means of inertial motion-capture driven musculoskeletal analysis. Our results showed that increased load carriage led to an increase in metabolic power and energy, changes in muscle parameters, a significant increase in completion time and heart rate, and changes in kinematic parameters. Despite the exploratory nature of this study, the proposed approach seems promising to obtain insight into the underlying mechanisms that result in performance degradation during load-carrying military activities.

Flexing and downsizing the femoral component is not detrimental to patellofemoral biomechanics in posterior-referencing cruciate-retaining total knee arthroplasty.

PURPOSE: When downsizing the femoral component to prevent mediolateral overhang, notching of the anterior femoral cortex may occur, which could be solved by flexing the femoral component. In this study, we investigated the effect of flexion of the femoral component on patellar tendon moment arm, patellofemoral forces and kinematics in posterior-referencing CR-TKA. Our hypothesis was that flexion of the femoral component increases the patellar tendon moment arm, reduces the patellofemoral forces and provides stable kinematics. METHODS: A validated musculoskeletal model of CR-TKA was used. The flexion of the femoral component was increased in four steps (0°, 3°, 6°, 9°) using posterior referencing, and different alignments were analysed in combination with three implant sizes (3, 4, 5). A chair-rising trial was analysed using the model, while simultaneously estimating quadriceps muscle force, patellofemoral contact force, tibiofemoral and patellofemoral kinematics. RESULTS: Compared to the reference case (size 4 and 0° flexion), for every 3° of increase in flexion of the femoral component the patellar tendon moment arm increased by 1% at knee extension. The peak quadriceps muscle force and patellofemoral contact force decreased by 2%, the patella shifted 0.8 mm more anteriorly and the remaining kinematics remained stable, with knee flexion. With the smaller size, the patellar tendon moment arm decreased by 6%, the quadriceps muscle force and patellofemoral contact force increased by 8 and 12%, and the patellar shifted 5 mm more posteriorly. Opposite trends were found with the bigger size. CONCLUSION: Flexing the femoral component with posterior referencing reduced the patellofemoral contact forces during a simulated chair-rising trial with a patient-specific musculoskeletal model of CR-TKA. There seems to be little risk when flexing and downsizing the femoral component, compared to when using a bigger size and neutral alignment. These findings provide relevant information to surgeons who wish to prevent anterior notching when downsizing the femoral component.

Anterior referencing of tibial slope in total knee arthroplasty considerably influences knee kinematics: a musculoskeletal simulation study.

PURPOSE: In total knee arthroplasty (TKA), the posterior tibial slope is not always reconstructed correctly, and the knee ligaments may become too tight in flexion. To release a tight flexion gap, surgeons can increase the posterior tibial slope using two surgical resection techniques: the anterior tibial cortex (ACR) or the centre of tibial plateau (CPR) referencing. It is not known how this choice affects the knee laxity and function during activities of daily living. The aim of this study was to investigate the effect of tibial slope on knee laxity, kinematics and forces during a squatting activity using computer simulation techniques. We hypothesised that the effects depend on the referencing technique utilised. METHODS: A validated musculoskeletal model of TKA was used. Knee laxity tests were simulated in flexion and extension. Then, a squat motion was simulated to calculate: movement of the tibiofemoral joint (TFJ) contact points and patello-femoral joint (PFJ) contact force. All analyses were repeated with more anterior (-3°), neutral (0°), and more posterior tibial slope (+3°, +6°, +9°), and with two referencing techniques (ACR, CPR). RESULTS: Knee laxities increased dramatically with more posterior slope with the ACR technique (up to 400%), both in flexion and in extension. The CPR technique, instead, had much smaller effects (up to 42% variations). During squatting, more slope with the ACR technique resulted in larger movements of the TFJ contact point. The PFJ contact force decreased considerably with more slope with the CPR technique (12% body weight reduction every 3° more posterior slope), thanks to the preservation of the patellar height and quadriceps-femur load sharing. CONCLUSION: ACR technique alters considerably the knee laxity, both in flexion and extensions, and surgeons should be cautious about its use. More slope with CPR technique induces more favourable TFJ kinematics and loading of the knee extensor apparatus and does not substantially alter knee laxity. Preferably, the tibial slope resection should be pre-planned thoroughly and performed using CPR technique as accurately as possible. Surgeons can directly translate the results of this study into the clinical practice.

A Novel Setup and Protocol to Measure the Range of Motion of the Wrist and the Hand.

The human hand is important for the performance of activities of daily living which are directly related to quality of life. Various conditions, such as Duchenne muscular dystrophy (DMD) can affect the function of the human hand and wrist. The ability to assess the impairment in the hand and the wrist by measuring the range of motion (ROM), is essential for the development of effective rehabilitation protocols. Currently the clinical standard is the goniometer. In this study we explore the feasibility and reliability of an optical sensor (Leap motion sensor) in measuring active hand/wrist ROM. We measured the hand/wrist ROM of 20 healthy adults with the goniometer and the Leap motion sensor, in order to check the agreement between the two methods and additionally, we performed a test-retest of the Leap motion sensor with 12 of them, to assess its reliability. The results suggest low agreement between the goniometer and the leap motion sensor, yet showing a large decrease in measurement time and high reliability when using the later. Despite the low agreement between the two methods, we believe that the Leap motion sensor shows potential to contribute to the development of hand rehabilitation protocols and be used with patients in a clinical setting.

Evaluation of a Surrogate Contact Model in Force-Dependent Kinematic Simulations of Total Knee Replacement.

Knowing the forces in the human body is of great clinical interest and musculoskeletal (MS) models are the most commonly used tool to estimate them in vivo. Unfortunately, the process of computing muscle, joint contact, and ligament forces simultaneously is computationally highly demanding. The goal of this study was to develop a fast surrogate model of the tibiofemoral (TF) contact in a total knee replacement (TKR) model and apply it to force-dependent kinematic (FDK) simulations of activities of daily living (ADLs). Multiple domains were populated with sample points from the reference TKR contact model, based on reference simulations and design-of-experiments. Artificial neural networks (ANN) learned the relationship between TF pose and loads from the medial and lateral sides of the TKR implant. Normal and right-turn gait, rising-from-a-chair, and a squat were simulated using both surrogate and reference contact models. Compared to the reference contact model, the surrogate contact model predicted TF forces with a root-mean-square error (RMSE) lower than 10 N and TF moments lower than 0.3 N·m over all simulated activities. Secondary knee kinematics were predicted with RMSE lower than 0.2 mm and 0.2 deg. Simulations that used the surrogate contact model ran on average three times faster than those using the reference model, allowing the simulation of a full gait cycle in 4.5 min. This modeling approach proved fast and accurate enough to perform extensive parametric analyses, such as simulating subject-specific variations and surgical-related factors in TKR.

Dynamic arm study: quantitative description of upper extremity function and activity of boys and men with duchenne muscular dystrophy.

BACKGROUND: Therapeutic management of upper extremity (UE) function of boys and men with Duchenne Muscular Dystrophy (DMD) requires sensitive and objective assessment. Therefore, we aimed to measure physiologic UE function of healthy subjects and DMD patients in different disease stages, and to evaluate the relation between these physiologic measures and functional UE scales. METHODS: Twenty-three DMD patients and twenty healthy controls (7-23 years) participated in this explorative case-control study. Maximal muscle torque, maximal and normalized surface electromyography (sEMG) amplitudes, muscle thickness, echogenicity and maximal passive and active joint angles were measured. At activity level, Brooke upper extremity rating scale and the Performance of Upper Limb (PUL) scale were used. RESULTS: Outcome measures related to proximal UE function could discriminate between disease stages. Increased normalized sEMG amplitudes were found in patients, even in early disease stages. Maximal active joint angles showed the strongest relation to Brooke scale (R 2 = 0.88) and PUL scale (R 2 = 0.85). CONCLUSIONS: The decline of muscle functions precedes the decline in performance of UE activities, and therefore may play a role in early detection of UE limitations. Increased sEMG levels demonstrate that DMD patients use more of their muscle capacity compared to healthy subjects, to perform daily activities. This might result in increased fatigability. Active maximal joint angles are highly related to functional scales, so preserving the ability to use the full range of motion is important for the performance of daily activities. Close monitoring of active joint angles could therefore help in starting interventions that minimize functional UE decline in DMD patients timely.

Surface EMG signals in very late-stage of Duchenne muscular dystrophy: a case study.

BACKGROUND: Robotic arm supports aim at improving the quality of life for adults with Duchenne muscular dystrophy (DMD) by augmenting their residual functional abilities. A critical component of robotic arm supports is the control interface, as is it responsible for the human-machine interaction. Our previous studies showed the feasibility of using surface electromyography (sEMG) as a control interface to operate robotic arm supports in adults with DMD (22-24 years-old). However, in the biomedical engineering community there is an often raised skepticism on whether adults with DMD at the last stage of their disease have sEMG signals that can be measured and used for control. FINDINGS: In this study sEMG signals from Biceps and Triceps Brachii muscles were measured for the first time in a 37 year-old man with DMD (Brooke 6) that lost his arm function 15 years ago. The sEMG signals were measured during maximal and sub-maximal voluntary isometric contractions and evaluated in terms of signal-to-noise ratio and co-activation ratio. Beyond the profound deterioration of the muscles, we found that sEMG signals from both Biceps and Triceps muscles were measurable in this individual, although with a maximum signal amplitude 100 times lower compared to sEMG from healthy subjects. The participant was able to voluntarily modulate the required level of muscle activation during the sub-maximal voluntary isometric contractions. Despite the low sEMG amplitude and a considerable level of muscle co-activation, simulations of an elbow orthosis using the measured sEMG as driving signal indicated that the sEMG signals of the participant had the potential to provide control of elbow movements. CONCLUSIONS: To the best of our knowledge this is the first time that sEMG signals from a man with DMD at the last-stage of the disease were measured, analyzed and reported. These findings offer promising perspectives to the use of sEMG as an intuitive and natural control interface for robotic arm supports in adults with DMD until the last stage of the disease.

Comparison between sEMG and force as control interfaces to support planar arm movements in adults with Duchenne: a feasibility study.

BACKGROUND: Adults with Duchenne muscular dystrophy (DMD) can benefit from devices that actively support their arm function. A critical component of such devices is the control interface as it is responsible for the human-machine interaction. Our previous work indicated that surface electromyography (sEMG) and force-based control with active gravity and joint-stiffness compensation were feasible solutions for the support of elbow movements (one degree of freedom). In this paper, we extend the evaluation of sEMG- and force-based control interfaces to simultaneous and proportional control of planar arm movements (two degrees of freedom). METHODS: Three men with DMD (18-23 years-old) with different levels of arm function (i.e. Brooke scores of 4, 5 and 6) performed a series of line-tracing tasks over a tabletop surface using an experimental active arm support. The arm movements were controlled using three control methods: sEMG-based control, force-based control with stiffness compensation (FSC), and force-based control with no compensation (FNC). The movement performance was evaluated in terms of percentage of task completion, tracing error, smoothness and speed. RESULTS: For subject S1 (Brooke 4) FNC was the preferred method and performed better than FSC and sEMG. FNC was not usable for subject S2 (Brooke 5) and S3 (Brooke 6). Subject S2 presented significantly lower movement speed with sEMG than with FSC, yet he preferred sEMG since FSC was perceived to be too fatiguing. Subject S3 could not successfully use neither of the two force-based control methods, while with sEMG he could reach almost his entire workspace. CONCLUSIONS: Movement performance and subjective preference of the three control methods differed with the level of arm function of the participants. Our results indicate that all three control methods have to be considered in real applications, as they present complementary advantages and disadvantages. The fact that the two weaker subjects (S2 and S3) experienced the force-based control interfaces as fatiguing suggests that sEMG-based control interfaces could be a better solution for adults with DMD. Yet force-based control interfaces can be a better alternative for those cases in which voluntary forces are higher than the stiffness forces of the arms.

Technical Aspects and Validation of a New Biofeedback System for Measuring Lower Limb Loading in the Dynamic Situation.

BACKGROUND: A variety of techniques for measuring lower limb loading exists, each with their own limitations. A new ambulatory biofeedback system was developed to overcome these limitations. In this study, we described the technical aspects and validated the accuracy of this system. METHODS: A bench press was used to validate the system in the static situation. Ten healthy volunteers were measured by the new biofeedback system and a dual-belt instrumented treadmill to validate the system in the dynamic situation. RESULTS: Bench press results showed that the sensor accurately measured peak loads up to 1000 N in the static situation. In the healthy volunteers, the load curves measured by the biofeedback system were similar to the treadmill. However, the peak loads and loading rates were lower in the biofeedback system in all participants at all speeds. CONCLUSIONS: Advanced sensor technologies used in the new biofeedback system resulted in highly accurate measurements in the static situation. The position of the sensor and the design of the biofeedback system should be optimized to improve results in the dynamic situation.

The effect of pressure and shear on tissue viability of human skin in relation to the development of pressure ulcers: a systematic review.

Pressure ulcers are a significant problem in health care, due to high costs and large impact on patients' life. In general, pressure ulcers develop as tissue viability decreases due to prolonged mechanical loading. The relation between load and tissue viability is highly influenced by individual characteristics. It is proposed that measurements of skin blood flow regulation could provide good assessment of the risk for pressure ulcer development, as skin blood flow is essential for tissue viability. . Therefore, the aim of this systematic review is to gain insight in the relation between mechanical load and the response of the skin and underlying tissue to this loading measured in-vivo with non-invasive techniques. A systematic literature search was performed to identify articles analysing the relation between mechanical load (pressure and/or shear) and tissue viability measured in-vivo. Two independent reviewers scored the methodological quality of the 22 included studies. Methodological information as well as tissue viability parameters during load application and after load removal were extracted from the included articles and used in a meta-analysis. Pressure results in a decrease in skin blood flow parameters, compared to baseline; showing a larger decrease with higher magnitudes of load. The steepness of the decrease is mostly dependent on the anatomical location. After load removal the magnitude of the post-reactive hyperaemic peak is related to the magnitude of pressure. Lastly, shear in addition to pressure, shows an additional negative effect, but the effect is less apparent than pressure on skin viability.

A subject-specific musculoskeletal modeling framework to predict in vivo mechanics of total knee arthroplasty.

Musculoskeletal (MS) models should be able to integrate patient-specific MS architecture and undergo thorough validation prior to their introduction into clinical practice. We present a methodology to develop subject-specific models able to simultaneously predict muscle, ligament, and knee joint contact forces along with secondary knee kinematics. The MS architecture of a generic cadaver-based model was scaled using an advanced morphing technique to the subject-specific morphology of a patient implanted with an instrumented total knee arthroplasty (TKA) available in the fifth "grand challenge competition to predict in vivo knee loads" dataset. We implemented two separate knee models, one employing traditional hinge constraints, which was solved using an inverse dynamics technique, and another one using an 11-degree-of-freedom (DOF) representation of the tibiofemoral (TF) and patellofemoral (PF) joints, which was solved using a combined inverse dynamic and quasi-static analysis, called force-dependent kinematics (FDK). TF joint forces for one gait and one right-turn trial and secondary knee kinematics for one unloaded leg-swing trial were predicted and evaluated using experimental data available in the grand challenge dataset. Total compressive TF contact forces were predicted by both hinge and FDK knee models with a root-mean-square error (RMSE) and a coefficient of determination (R2) smaller than 0.3 body weight (BW) and equal to 0.9 in the gait trial simulation and smaller than 0.4 BW and larger than 0.8 in the right-turn trial simulation, respectively. Total, medial, and lateral TF joint contact force predictions were highly similar, regardless of the type of knee model used. Medial (respectively lateral) TF forces were over- (respectively, under-) predicted with a magnitude error of M < 0.2 (respectively > -0.4) in the gait trial, and under- (respectively, over-) predicted with a magnitude error of M > -0.4 (respectively < 0.3) in the right-turn trial. Secondary knee kinematics from the unloaded leg-swing trial were overall better approximated using the FDK model (average Sprague and Geers' combined error C = 0.06) than when using a hinged knee model (C = 0.34). The proposed modeling approach allows detailed subject-specific scaling and personalization and does not contain any nonphysiological parameters. This modeling framework has potential applications in aiding the clinical decision-making in orthopedics procedures and as a tool for virtual implant design.

Erratum to: Design and pilot validation of A-gear: a novel wearable dynamic arm support.

Unfortunately, the original version of this article [1] contained an error. Equation 6 was included incorrectly: in the original equation variable slinks3 was missing.The correct Equation 6 can be found below:

Design and pilot validation of A-gear: a novel wearable dynamic arm support.

BACKGROUND: Persons suffering from progressive muscular weakness, like those with Duchenne muscular dystrophy (DMD), gradually lose the ability to stand, walk and to use their arms. This hinders them from performing daily activities, social participation and being independent. Wheelchairs are used to overcome the loss of walking. However, there are currently few efficient functional substitutes to support the arms. Arm supports or robotic arms can be mounted to wheelchairs to aid in arm motion, but they are quite visible (stigmatizing), and limited in their possibilities due to their fixation to the wheelchair. The users prefer inconspicuous arm supports that are comfortable to wear and easy to control. METHODS: In this paper the design, characterization, and pilot validation of a passive arm support prototype, which is worn on the body, is presented. The A-gear runs along the body from the contact surface between seat and upper legs via torso and upper arm to the forearm. Freedom of motion is accomplished by mechanical joints, which are nearly aligned with the human joints. The system compensates for the arm weight, using elastic bands for static balance, in every position of the arm. As opposed to existing devices, the proposed kinematic structure allows trunk motion and requires fewer links and less joint space without compromising balancing precision. The functional prototype has been validated in three DMD patients, using 3D motion analysis. RESULTS: Measurements have shown increased arm performance when the subjects were wearing the prototype. Upward and forward movements were easier to perform. The arm support is easy to put on and remove. Moreover, the device felt comfortable for the subjects. However, downward movements were more difficult, and the patients would prefer the device to be even more inconspicuous. CONCLUSION: The A-gear prototype is a step towards inconspicuousness and therefore well-received dynamic arm supports for people with muscular weakness.

Non-invasive control interfaces for intention detection in active movement-assistive devices.

Active movement-assistive devices aim to increase the quality of life for patients with neuromusculoskeletal disorders. This technology requires interaction between the user and the device through a control interface that detects the user's movement intention. Researchers have explored a wide variety of invasive and non-invasive control interfaces. To summarize the wide spectrum of strategies, this paper presents a comprehensive review focused on non-invasive control interfaces used to operate active movement-assistive devices. A novel systematic classification method is proposed to categorize the control interfaces based on: (I) the source of the physiological signal, (II) the physiological phenomena responsible for generating the signal, and (III) the sensors used to measure the physiological signal. The proposed classification method can successfully categorize all the existing control interfaces providing a comprehensive overview of the state of the art. Each sensing modality is briefly described in the body of the paper following the same structure used in the classification method. Furthermore, we discuss several design considerations, challenges, and future directions of non-invasive control interfaces for active movement-assistive devices.

Evaluation of EMG, force and joystick as control interfaces for active arm supports.

BACKGROUND: The performance capabilities and limitations of control interfaces for the operation of active movement-assistive devices remain unclear. Selecting an optimal interface for an application requires a thorough understanding of the performance of multiple control interfaces. METHODS: In this study the performance of EMG-, force- and joystick-based control interfaces were assessed in healthy volunteers with a screen-based one-dimensional position-tracking task. The participants had to track a target that was moving according to a multisine signal with a bandwidth of 3 Hz. The velocity of the cursor was proportional to the interface signal. The performance of the control interfaces were evaluated in terms of tracking error, gain margin crossover frequency, information transmission rate and effort. RESULTS: None of the evaluated interfaces was superior in all four performance descriptors. The EMG-based interface was superior in tracking error and gain margin crossover frequency compared to the force- and the joystick-based interfaces. The force-based interface provided higher information transmission rate and lower effort than the EMG-based interface. The joystick-based interface did not present any significant difference with the force-based interface for any of the four performance descriptors. We found that significant differences in terms of tracking error and information transmission rate were present beyond 0.9 and 1.4 Hz respectively. CONCLUSIONS: Despite the fact that the EMG-based interface is far from the natural way of interacting with the environment, while the force-based interface is closer, the EMG-based interface presented very similar and for some descriptors even a better performance than the force-based interface for frequencies below 1.4 Hz. The classical joystick presented a similar performance to the force-based interface and holds the advantage of being a well established interface for the control of many assistive devices. From these findings we concluded that all the control interfaces considered in this study can be regarded as a candidate interface for the control of an active arm support.

The Simultaneous Model-Based Estimation of Joint, Muscle, and Tendon Stiffness is Highly Sensitive to the Tendon Force-Strain Relationship.

OBJECTIVE: Accurate estimation of stiffness across anatomical levels (i.e., joint, muscle, and tendon) in vivo has long been a challenge in biomechanics. Recent advances in electromyography (EMG)-driven musculoskeletal modeling have allowed the non-invasive estimation of stiffness during dynamic joint rotations. Nevertheless, validation has been limited to the joint level due to a lack of simultaneous in vivo experimental measurements of muscle and tendon stiffness. METHODS: With a focus on the triceps surae, we employed a novel perturbation-based experimental technique informed by dynamometry and ultrasonography to derive reference stiffness at the joint, muscle, and tendon levels simultaneously. Here, we propose a new EMG-driven model-based approach that does not require external joint perturbation, nor ultrasonography, to estimate multi-level stiffness. We present a novel set of closed-form equations that enables the person-specific tuning of musculoskeletal parameters dictating biological stiffness, including passive force-length relationships in modeled muscles and tendons. RESULTS: Calibrated EMG-driven musculoskeletal models estimated the reference data with average normalized root-mean-square error ≈ 20%. Moreover, only when calibrated tendons were approximately four times more compliant than typically modeled, our approach could estimate multi-level reference stiffness. CONCLUSION: EMG-driven musculoskeletal models can be calibrated on a larger set of reference data to provide more realistic values for the biomechanical variables across multiple anatomical levels. Moreover, the tendon models that are typically used in musculoskeletal modeling are too stiff. SIGNIFICANCE: Calibrated musculoskeletal models informed by experimental measurements give access to an augmented range of biomechanical variables that might not be easily measured with sensors alone.

Numerical study of osteophyte effects on preoperative knee functionality in patients undergoing total knee arthroplasty.

Osteophytes are routinely removed during total knee arthroplasty, yet the preoperative planning currently relies on preoperative computed tomography (CT) scans of the patient's osteoarthritic knee, typically including osteophytic features. This complicates the surgeon's ability to anticipate the exact biomechanical effects of osteophytes and the consequences of their removal before the operation. The aim of this study was to investigate the effect of osteophytes on ligament strains and kinematics, and ascertain whether the osteophyte volume and location determine the extent of this effect. We segmented preoperative CT scans of 21 patients, featuring different osteophyte severity, using image-based active appearance models trained to identify the osteophytic and preosteophytic bone geometries and estimate the cartilage thickness in the segmented surfaces. The patients' morphologies were used to scale a template musculoskeletal knee model. Osteophytes induced clinically relevant changes to the knee's functional behavior, but these were variable and patient-specific. Generally, severe osteophytic knees significantly strained the oblique popliteal ligament (OPL) and posterior capsule (PC) relative to the preosteophytic state. Furthermore, there was a marked effect on the lateral collateral ligament and anterolateral ligament (ALL) strains compared to mild and moderate osteophytic knees, and concurrent alterations in the tibial lateral-medial translation and external-internal rotation. We found a strong correlation between the OPL, PC, and ALL strains and posterolateral condylar and tibial osteophytes, respectively. Our findings may have implications for the preoperative planning in total knee arthroplasty, toward reproducing the physiological knee biomechanics as close as feasibly possible.