AdjuSST: An Adjustable Surface Stiffness Treadmill.

Humans have the remarkable ability to manage foot-ground interaction seamlessly across terrain changes despite the high dynamic complexity of the task. Understanding how adaptation in the neuromotor system enables this level of robustness in the face of changing interaction dynamics is critical for developing more effective gait retraining interventions. We developed an adjustable surface stiffness treadmill (AdjuSST) to trigger these adaptation mechanisms and enable studies to better understand human adaptation to changing foot-ground dynamics. The AdjuSST system makes use of fundamental beam-bending principles; it controls surface stiffness by controlling the effective length of a cantilever beam. The beam acts as a spring suspension for the transverse endpoint load applied through the treadmill. The system is capable of enforcing a stiffness range of 15-300kN/m within 340 ms, deflecting linearly downwards up to 10 cm, and comfortably accommodating two full steps of travel along the belt. AdjuSST offers significant enhancements in effective walking surface length compared to similar systems, while also maintaining a useful stiffness range and responsive spring suspension. These improvements enhance our ability to study locomotor control and adaptation to changes in surface stiffness, as well as provide new avenues for gait rehabilitation.

NSF DARE-transforming modeling in neurorehabilitation: a patient-in-the-loop framework.

In 2023, the National Science Foundation (NSF) and the National Institute of Health (NIH) brought together engineers, scientists, and clinicians by sponsoring a conference on computational modelling in neurorehabiilitation. To facilitate multidisciplinary collaborations and improve patient care, in this perspective piece we identify where and how computational modelling can support neurorehabilitation. To address the where, we developed a patient-in-the-loop framework that uses multiple and/or continual measurements to update diagnostic and treatment model parameters, treatment type, and treatment prescription, with the goal of maximizing clinically-relevant functional outcomes. This patient-in-the-loop framework has several key features: (i) it includes diagnostic and treatment models, (ii) it is clinically-grounded with the International Classification of Functioning, Disability and Health (ICF) and patient involvement, (iii) it uses multiple or continual data measurements over time, and (iv) it is applicable to a range of neurological and neurodevelopmental conditions. To address the how, we identify state-of-the-art and highlight promising avenues of future research across the realms of sensorimotor adaptation, neuroplasticity, musculoskeletal, and sensory & pain computational modelling. We also discuss both the importance of and how to perform model validation, as well as challenges to overcome when implementing computational models within a clinical setting. The patient-in-the-loop approach offers a unifying framework to guide multidisciplinary collaboration between computational and clinical stakeholders in the field of neurorehabilitation.

Gait Adaptation to Asymmetric Hip Stiffness Applied by a Robotic Exoskeleton.

Wearable exoskeletons show significant potential for improving gait impairments, such as interlimb asymmetry. However, a more profound understanding of whether exoskeletons are capable of eliciting neural adaptation is needed. This study aimed to characterize how individuals adapt to bilateral asymmetric joint stiffness applied by a hip exoskeleton, similar to split-belt treadmill training. Thirteen unimpaired individuals performed a walking trial on the treadmill while wearing the exoskeleton. The right side of the exoskeleton acted as a positive stiffness torsional spring, pulling the thigh towards the neutral standing position, while the left acted as a negative stiffness spring pulling the thigh away from the neutral standing position. The results showed that this intervention applied by a hip exoskeleton elicited adaptation in spatiotemporal and kinetic gait measures similar to split-belt treadmill training. These results demonstrate the potential of the proposed intervention for retraining symmetric gait.

Editorial Commentary: Utility of Patient-Reported Outcome Threshold Scores to Estimate Patient Satisfaction: 'Let's Ask the Patient!'

The reporting and analysis of patient-reported outcome measures have come a long way. Since the concept of the minimally clinically important difference was first introduced in 1989, threshold scores have grown to include substantial clinical benefit and patient acceptable symptomatic state (PASS). The initial motivation for developing these thresholds was rooted in separating clinical significance from statistical. These thresholds provide insight into the relationship between scores on patient-reported outcome measures (PROM) and patient-reported improvement and satisfaction. It follows that in order to evaluate PROM scores, the best method for deriving the threshold typically uses an anchor-based methodology, i.e., "ask the patient." Specifically, patients are asked how much change they've experienced and whether they consider their current state to be satisfactory. The responses to these questions are compared with the scores on PROMs to find outcome thresholds that best separate patients who reported no improvement from those who reported minimal improvement, substantial improvement, and satisfaction with their current state of health (PASS). The PASS is of particular importance as it speaks to what arguably matters most to patients-a satisfactory state of health. Finally, viewing the PASS from the perspective of variation from study to study rather than as a uniform classifier is needed to make use of the growing number of papers reporting these thresholds. Examining differences in PASS values across papers can provide insight into how well PROM scores reflect patient satisfaction in different settings.

Hemoglobin A1c Levels >6.6% Are Associated With Higher Postoperative Complications After Anterior Cruciate Ligament Reconstruction.

Purpose: To investigate the relation between hemoglobin A1c (HbA1c) levels and postoperative complications after primary anterior cruciate ligament reconstruction (ACLR). Methods: A retrospective review was performed of consecutive patients with an isolated anterior cruciate ligament tear, preoperative diagnosis of diabetes, and documented HbA1c within 90 days of primary ACLR between 2000 and 2019. Data collected included demographic and surgical characteristics, 90-day medical complications, and subsequent surgeries on the ipsilateral knee. A receiver operating curve was constructed for each HbA1c level in relation to postoperative complications and the optimal cutoff identified via Youden's J statistic. Multivariable logistic regression was performed to assess the relation between postoperative complications and age, sex, graft type, diabetes subtype, and HbA1c. Results: Nineteen patients (7 females, 12 males) fulfilled inclusion criteria with preoperative HbA1c ranging from 5.5 to 10. Complications included septic knee (n = 1) and cyclops lesions requiring arthroscopic lysis (n = 3). Patients with HbA1c of 6.7% or higher were 25 times more likely to experience any postoperative complication (P = .04) and 16 times more likely to require lysis of adhesions (P = .08). On multivariable regression, HbA1c remained significantly associated with any complication (P = .005) and developing arthrofibrosis (P = .02) independent of age, sex, graft type, and diabetes subtype. Conclusions: Diabetic patients undergoing primary ACLR with a preoperative HbA1c of 6.7% or higher were 25 times more likely to require repeat surgical intervention for a postoperative complication. These complications included arthrofibrosis and infection. Strict glycemic control may help minimize the risk of postoperative complications after ACLR. Level of Evidence: Level III, retrospective cohort study.

Let's talk about it: an exploration of the comparative use of three different digital platforms to gather patient-reported outcome measures.

BACKGROUND: Patient-reported outcome (PRO) measures provide valuable evidence in clinical trials; however, poor compliance with PRO measures is a notable and long-standing problem, resulting in missing data that potentially impact the interpretation of trial results. Interactive, patient-centric platforms may increase participants' motivation to complete PRO measures over the course of a clinical trial. Thus, the aim of this study was to evaluate and optimize the usability of 3 popular consumer technologies-a traditional app-based interface, a chatbot interface, and a speech-operated interface-that may be used to improve user engagement and compliance with PRO measures. METHODS: Participants aged 18-75 years from the general United States population tested the usability of 3 ePRO platforms: a traditional app-based interface using Datacubed Health Platform (Datacubed), a web-based chatbot interface using the Orbita platform, and a speech-operated Alexa interface using an Alexa Skill called "My Daily Wellness." The usability of these platforms was tested with 2 PRO measures: the EQ-5D-5 L and the SF-12v2 Health Survey (SF-12v2), Daily recall. Using a crossover design, 3 cohorts of participants tested each ePRO platform daily for 1 week. After testing, interviews were conducted regarding the participants' experience with each platform. RESULTS: A total of 24 adults participated in the study. The mean age of participants was 45 years (range, 21-71 years), and half were female (n = 12; 50%). Overall, participants prioritized speed, ease of use, and device portability in selecting their preferred platform. The Datacubed app met these criteria and was the preferred platform among most participants (n = 20; 83%). Participants also suggested various modifications to the platforms, such as programmable notifications, adjustable speed, and additional daily reminders. CONCLUSIONS: These data demonstrate the importance of speed, ease of use, and device portability, features that are currently incorporated in the Datacubed app, in ePRO platforms used in future clinical trials. Additionally, the usability of ePRO platforms may be optimized by adding programmable notifications, adjustable speed, and increased daily reminders. The results of this study may be used to enhance the usability and patient centricity of these platforms to improve user compliance and engagement during clinical trials.

Gait adaptation to asymmetric hip stiffness applied by a robotic exoskeleton.

Wearable exoskeletons show significant potential for improving gait impairments, such as interlimb asymmetry. However, a more profound understanding of whether exoskeletons are capable of eliciting neural adaptation is needed. This study aimed to characterize how individuals adapt to bilateral asymmetric joint stiffness applied by a hip exoskeleton, similar to split-belt treadmill training. Thirteen unimpaired individuals performed a walking trial on the treadmill while wearing the exoskeleton. The right side of the exoskeleton acted as a positive stiffness torsional spring, pulling the thigh towards the neutral standing position, while the left acted as a negative stiffness spring pulling the thigh away from the neutral standing position. The results showed that this intervention applied by a hip exoskeleton elicited adaptation in spatiotemporal and kinetic gait measures similar to split-belt treadmill training. These results demonstrate the potential of the proposed intervention for retraining symmetric gait.

Definition of factor Xa inhibitor-related, life-threatening gastrointestinal bleeding and guidance on when to use reversal therapy: A Delphi panel.

Objective: To define and contextualize life-threatening gastrointestinal (GI) bleeding in the setting of factor Xa (FXa) inhibitor therapy and to derive a consensus-based, clinically oriented approach to the administration of FXa inhibitor reversal therapy. Methods: We convened an expert panel of clinicians representing specialties in emergency medicine, gastroenterology, vascular medicine, and trauma surgery. Consensus was reached among the clinician panelists using the Delphi technique, which consisted of 2 survey questionnaires followed by virtual, real-time consensus-building exercises. Results: Hypovolemia and hemodynamic instability were considered the most important clinical signs of FXa inhibitor-related, life-threatening GI bleeds. Clinician panelists agreed that potentially life-threatening GI bleeding should be determined on the basis of hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. Last, the panel agreed that all patients with life-threatening, FXa inhibitor-associated GI bleeding should be considered for FXa inhibitor reversal therapy; the decision to reverse FXa inhibition should be individualized, weighing the risks and benefits of reversal; and when reversal is elected, therapy should be administered within 1 h after initial emergency department evaluation, when possible. Conclusions: Consensus-based definitions of life-threatening GI bleeding and approaches to FXa inhibitor reversal centered on hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. The results from this Delphi panel may inform clinical decision-making for the treatment of patients experiencing GI bleeding associated with FXa inhibitor use in the emergency department setting.

Acromioclavicular Joint Anatomy and Biomechanics: The Significance of Posterior Rotational and Translational Stability.

The shoulder girdle extends from the sternoclavicular joint to the scapular stabilizing muscles posteriorly. It consists of 3 joints and 2 mobile regions. The shoulder girdle is statically stabilized by the acromioclavicular and coracoclavicular capsuloligamentous structures and dynamically stabilized by the trapezius, deltoid, and deltotrapezial fascia. During humerothoracic elevation, the clavicle elevates, protracts, and rotates posteriorly through the sternoclavicular joint while the scapula tilts posteriorly and rotates upward. The purpose of this article is to review the anatomy and biomechanics of the acromioclavicular joint and the shoulder girdle.

Prehospital Treatment of Benzodiazepine-Resistant Pediatric Status Epilepticus with Parenteral Ketamine: A Case Series.

We report the initial six pediatric patients treated with ketamine for benzodiazepine-resistant status epilepticus in an urban, ground-based emergency medical services (EMS) system. Evidence for ketamine as a second-line agent for both adult and pediatric refractory seizure activity in the hospital setting has increased over the past decade. The availability of an inexpensive and familiar second-line prehospital anti-epileptic drug option is extremely desirable. We believe these initial data demonstrate promising seizure control effects without significant respiratory depression, indicating a potential role for ketamine in the EMS treatment of pediatric benzodiazepine-refractory seizures.

Asymmetric shoe height induces reactive changes in gait kinematics but not kinetics in healthy young adults.

BACKGROUND: Footwear interventions are a potential avenue to correct walking asymmetry in neurologic populations, such as stroke. However, the motor learning mechanisms that underlie the changes in walking imposed by asymmetric footwear are unclear. RESEARCH QUESTION: The objectives of this study were to examine symmetry changes during and after an asymmetric shoe height intervention in (1) vertical impulse and (2) spatiotemporal gait parameters and (3) joint kinematics, in healthy young adults METHODS: Eleven healthy young adults (3 males, 8 females; 21.2 ± 3.1 years old) participated in this study. Participants walked on an instrumented treadmill at 1.3 m/s for four conditions: (1) a 5-minute familiarization with equal shoe height, (2) a 5-minute baseline with equal shoe height, (3) a 10-minute intervention, where participants walked with asymmetric shoe height with a 10 mm shoe insert in one shoe, and (4) a 10-minute post-intervention, where participants walked with equal shoe height. Asymmetry in kinetics and kinematics were used to identify changes during intervention and aftereffects, a hallmark of feedforward adaptation RESULTS: Participants did not alter vertical impulse asymmetry (p = 0.667) nor stance time asymmetry (p = 0.228). During the intervention, step time asymmetry (p = 0.003) and double support asymmetry (p < 0.001) were greater compared to baseline. Leg joint asymmetry during stance (Ankle plantarflexion: p < 0.001; Knee flexion: p < 0.001; Hip extension: p = 0.011) was greater during the intervention compared to baseline. However, changes in spatiotemporal gait variables and joint mechanics did not demonstrate aftereffects. SIGNIFICANCE: Our results show that healthy human adults change gait kinematics, but not weight-bearing symmetry with asymmetrical footwear. This suggests that healthy humans prioritize maintaining vertical impulse by changing their kinematics. Further, the changes in gait kinematics are short-lived, suggesting feedback-based control, and a lack of feedforward motor adaptations.

Minimum effort simulations of split-belt treadmill walking exploit asymmetry to reduce metabolic energy expenditure.

Walking on a split-belt treadmill elicits an adaptation response that changes baseline step length asymmetry. The underlying causes of this adaptation, however, are difficult to determine. It has been proposed that effort minimization may drive this adaptation, based on the idea that adopting longer steps on the fast belt, or positive step length asymmetry (SLA), can cause the treadmill to exert net-positive mechanical work on a bipedal walker. However, humans walking on split-belt treadmills have not been observed to reproduce this behavior when allowed to freely adapt. To determine if an effort-minimization motor control strategy would result in experimentally observed adaptation patterns, we conducted simulations of walking on different combinations of belt speeds with a human musculoskeletal model that minimized muscle excitations and metabolic rate. The model adopted increasing amounts of positive SLA and decreased its net metabolic rate with increasing belt speed difference, reaching +42.4% SLA and -5.7% metabolic rate relative to tied-belt walking at our maximum belt speed ratio of 3:1. These gains were primarily enabled by an increase in braking work and a reduction in propulsion work on the fast belt. The results suggest that a purely effort minimization driven split-belt walking strategy would involve substantial positive SLA, and that the lack of this characteristic in human behavior points to additional factors influencing the motor control strategy, such as aversion to excessive joint loads, asymmetry, or instability.NEW & NOTEWORTHY Behavioral observations of split-belt treadmill adaptation have been inconclusive toward its underlying causes. To estimate gait patterns when driven exclusively by one of these possible underlying causes, we simulated split-belt treadmill walking with a musculoskeletal model that minimized its summed muscle excitations. Our model took significantly longer steps on the fast belt and reduced its metabolic rate below tied-belt walking, unlike experimental observations. This suggests that asymmetry is energetically optimal, but human adaptation involves additional factors.

Bilateral asymmetric hip stiffness applied by a robotic hip exoskeleton elicits kinematic and kinetic adaptation.

Wearable robotic exoskeletons hold great promise for gait rehabilitation as portable, accessible tools. However, a better understanding of the potential for exoskeletons to elicit neural adaptation-a critical component of neurological gait rehabilitation-is needed. In this study, we investigated whether humans adapt to bilateral asymmetric stiffness perturbations applied by a hip exoskeleton, taking inspiration from asymmetry augmentation strategies used in split-belt treadmill training. During walking, we applied torques about the hip joints to repel the thigh away from a neutral position on the left side and attract the thigh toward a neutral position on the right side. Six participants performed an adaptation walking trial on a treadmill while wearing the exoskeleton. The exoskeleton elicited time-varying changes and aftereffects in step length and propulsive/braking ground reaction forces, indicating behavioral signatures of neural adaptation. These responses resemble typical responses to split-belt treadmill training, suggesting that the proposed intervention with a robotic hip exoskeleton may be an effective approach to (re)training symmetric gait.

The Use of Biologics in NFL Athletes: An Expert Consensus of NFL Team Physicians.

Background: There is a lack of published information outlining the use of biologics in National Football League (NFL) athletes and limited data to guide biologic treatment strategies. Purpose: To develop a consensus on the use of biologics among NFL team physicians. Study Design: Consensus statement. Methods: A working group of 6 experts convened a consensus process involving NFL team physicians using validated Delphi methodology. Physicians from 32 NFL teams as well as NFL London were invited to take part. This iterative process was used to define statements on the use of biologics in NFL athletes. A recent scoping review exploring biologics in professional athletes was used to inform the first of 3 rounds of surveys, with statements considered under 7 headings: biologics in general, challenges of treating NFL athletes, terminology/nomenclature, autologous blood products, cell-based therapies, guidance for NFL team physicians, and biologic research in the NFL. In addition to rating agreement, experts were encouraged to propose further items or modifications. Predefined criteria were used to refine item lists after each survey. For a consensus within the final round, defined a priori, items were included in the final information set if a minimum of 75% of respondents agreed and fewer than 10% disagreed. Results: Physicians from 26 NFL teams and NFL London responded to the initial invitation to participate in the Delphi process; 88.9% of participating team physicians completed the round 1 survey, with response rates of 87.5% in round 2 and 95.2% in round 3. After 3 rounds, 47 statements reached a consensus. A consensus was achieved that platelet-rich plasma has a positive impact on patellar tendinopathy and on symptoms in early osteoarthritis but not for other indications. NFL team physicians agreed that while cell therapies have the potential to improve symptoms, the misrepresentation of uncharacterized preparations as "stem cells" has contributed to the widespread use of unproven therapies. Conclusion: This study established an expert consensus on 47 statements relating to the use of biologics in NFL athletes. In addition to providing clinical guidance for the use of biologics in NFL athletes, this study identified key areas for future focus including the development of athlete education materials.

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib.

Aim: To assess real-world clinical outcomes in patients with non-small-cell lung cancer with MET exon 14 skipping mutation and brain metastases (BM) who received capmatinib, a recently approved MET inhibitor, in routine US clinical practice. Materials & methods: Patient data were collected using a retrospective medical record review, led by participating oncologists. Eligible patients initiated treatment with capmatinib in any line, after BM diagnosis, between May 2020 and June 2021. Data on real-world overall response rate (rwORR) and real-world progression-free survival (rwPFS) were descriptively analyzed. Results: 68 eligible patients were analyzed. In patients treated with first-line (1L) capmatinib (n = 55), the rwORR was 90.9% systemically and 87.3% intracranially; median systemic rwPFS was 14.1 months. Among radiation-naive patients on 1L capmatinib (n = 20), rwORR was 85.0%, both systemically and intracranially; median systemic rwPFS was 14.1 months. Conclusion: This study showed substantial systemic and intracranial effectiveness for capmatinib in real-world setting; findings were consistent for RT-naive patients.

Editorial Commentary: Fascia Lata Allograft for Shoulder Superior Capsular Reconstruction: In the Fight Over Optimal Graft Choice for Irreparable Rotator Cuff Tears, Superior Capsular Reconstruction Proponents May Be Changing Their Gloves.

Optimal treatment of irreparable rotator cuff tears is still debated. Proponents of the superior capsule reconstruction (SCR) have previously used fascia lata autograft and acellular dermal allograft. Interest is growing in using fascia lata allograft as a new graft material. Well-designed biomechanical studies are important to understand the mechanical properties of the superior capsular tissue and fascia lata allograft. Recent biomechanical research shows that fascia lata allograft has similar initial stiffness (over the first 2 mm) and ultimate load compared to the native superior capsule. That said, ultimate load is the load at which a construct fails, whereas the yield point is the load on the stress-strain curve at which a material transitions from elastic to plastic deformation. In the shoulder where the SCR, for example, is going to be repetitively loaded, it is potentially more meaningful to talk about the yield point in order to stay within the elastic range. Using this framework, the yield point for fascia lata allograft is approximately one third the yield point of native capsular tissue. Additionally, "initial" stiffness is not the entire story. At greater loads, fascia lata allograft has higher displacement compared to native tissue. Of importance, fascia lata allograft failed by sutures slowly cutting through the allograft tissue; this may represent a limitation of the construct that could be addressed using stitch configurations resistant to cut through. Fascia lata allograft is a promising solution for SCR. Biomechanical studies require nuanced interpretation, and most of all, do not evaluate clinical healing.

Understanding the Patient Experience of Hunger and Improved Quality of Life with Setmelanotide Treatment in POMC and LEPR Deficiencies.

INTRODUCTION: In patients with pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency, managing obesity and hyperphagia can be burdensome for patients and caretakers. The impacts on health-related quality of life are under-recognized and are not well characterized. METHODS: We conducted in-depth qualitative interviews in patients with POMC (n = 3) and LEPR (n = 2) deficiencies participating in an ongoing open-label extension of phase 3 clinical trials with the melanocortin receptor 4 agonist setmelanotide to describe the patient experience of hyperphagia and characterize changes following treatment with setmelanotide. RESULTS: Prior to setmelanotide treatment, all five patients described abnormal sensations of hunger with none indicating feeling satiated after meals and also reported that the burden of hyperphagia impacted their families, emotions, and work and/or school functioning. Following setmelanotide treatment, all five patients reported consistent reductions in hunger and weight, decreased eating, and feeling satiated after meals in addition to substantial improvements in each area of functioning they had previously reported. All five patients indicated they were very satisfied with the impact of setmelanotide on their quality of life and would be upset if treatment was discontinued. CONCLUSIONS: In patients with POMC or LEPR deficiency, hyperphagia and the inability to feel satiety negatively impacted quality of life. By reducing hunger and improving satiety, setmelanotide facilitated important changes in the lives of these patients. This qualitative research study suggests that the impact of setmelanotide goes beyond favorable clinical changes (e.g., weight and hunger) to also include quality of life improvements that are highly meaningful to patients.