Effects of Arthroscopic Surgery and Non-Surgical Therapy on Hip Contact Forces in Femoroacetabular Impingement Syndrome.

Introduction: We compared the 12-months effects of arthroscopic surgery and physiotherapist-led care for femoroacetabular impingement (FAI) syndrome on the time-varying magnitude of hip contact force and muscle contributions to hip contact force during walking.

Methods: Secondary analysis was performed on thirty-seven individuals with FAI syndrome who received biomechanical assessment before and 12-months following either arthroscopic surgery (n = 17) or physiotherapist-led care (Personalised Hip Therapy, PHT) (n = 20). At both time points, three-dimensional whole-body motions, ground reaction forces, and surface electromyograms (n = 14) were acquired during overground walking.

MuscleMap: An Open-Source, Community-Supported Consortium for Whole-Body Quantitative MRI of Muscle.

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates.

Bayesian modeling for analyzing heterogeneous response in preclinical mouse tumor models.

In anticancer research, tumor growth measured in mouse models is important for assessing treatment efficacy for a treatment to progress to human clinical trials. Statistical analysis of time-to-event tumor volume data is complex because of heterogeneity in response and welfare-related data loss. Traditional statistical methods of testing the mean difference between groups are not robust because they assume common responses across a population.

Building the OAChangeMap to Improve the Service Delivery of the New South Wales Osteoarthritis Chronic Care Program: A Worked Example of Using a Codesign Framework.

Objective: The Osteoarthritis Chronic Care Program (OACCP) has been implemented in Australian public hospitals to deliver best evidence osteoarthritis (OA) care. It is important to ensure that the OACCP continues to deliver evidence-based OA care as intended. We aimed to identify barriers and enablers to delivering the OACCP, prioritize the barriers, and generate strategies to address them.

A mechanistic PK/PD model of AZD0171 (anti-LIF) to support Phase II dose selection.

AZD0171 (INN: Falbikitug) is being developed as a humanized monoclonal antibody (mAb), immunoglobulin G subclass 1 (IgG1), which binds specifically to the immunosuppressive human cytokine leukemia inhibitory factor (LIF) and inhibits downstream signaling by blocking recruitment of glycoprotein 130 (gp130) to the LIF receptor (LIFR) subunit (gp190) and the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and is intended to treat adult participants with advanced solid tumors. LIF is a pleiotropic cytokine (and a member of the IL-6 family of cytokines) involved in many physiological and pathological processes and is highly expressed in a subset of solid tumors, including non-small cell lung cancer (NSCLC), colon, ovarian, prostate, and pancreatic cancer. The aim of this work was to develop a mechanistic PK/PD model to investigate the effect of AZD0171 on tumor LIF levels, predict the level of downstream signaling complex (LIF:LIFR:gp130) inhibition, and examine the dose-response relationship to support dose selection for a Phase II clinical study.

Squatting biomechanics following physiotherapist-led care or hip arthroscopy for femoroacetabular impingement syndrome: a secondary analysis from a randomised controlled trial.

Background: Femoroacetabular impingement syndrome (FAIS) can cause hip pain and chondrolabral damage that may be managed non-operatively or surgically. Squatting motions require large degrees of hip flexion and underpin many daily and sporting tasks but may cause hip impingement and provoke pain. Differential effects of physiotherapist-led care and arthroscopy on biomechanics during squatting have not been examined previously.

How Does Osteoarthritis Education Influence Knowledge, Beliefs, and Behavior in People With Knee and Hip Osteoarthritis? A Systematic Review.

Objective: Our goal was to inform the design and implementation of osteoarthritis (OA) education for people with knee and hip OA. This review investigated the impact of OA education on knowledge, beliefs, and behavior and how and why these changes occur.

Methods: Five databases-MEDLINE, Excerpta Medica Database (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Physiotherapy Evidence Database (PEDro)-were searched in August 2023.

Report of similar placebo response in one internet versus onsite randomised controlled trials from the literature.

Objective: The aim of this study was to compare the magnitude and the predictors of the placebo response in an internet versus onsite randomised controlled trials (RCTs) in people with hand osteoarthritis (HOA).

Method: This study is a analysis based on one internet RCT (RADIANT) and previously published onsite RCTs for HOA identified through a rigorous searching and selection strategy. The magnitude of the placebo response in the two different types of RCTs were compared using heterogeneity statistics and forest plots visualisation.

Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.

CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205).

Improving musculoskeletal physiotherapists' confidence in patient-centred care informed by acceptance and commitment therapy: A descriptive study.

Background: Patient-centred care is essential for high quality musculoskeletal care, however, few evidence-based opportunities exist that address the barriers to implementation for clinicians.

Objective: To develop and evaluate a simulation-based educational strategy for musculoskeletal physiotherapists to increase knowledge and confidence in patient-centred care.

Methods: Repeated-measures, single-group educational interventional descriptive study.

CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK-Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits.

Lessons learnt from a nationally funded training and mentoring programme for early-mid career musculoskeletal researchers in Australia.

Introduction: Quality training and mentoring are crucial components of successful career development for early mid career researchers (EMCRs). This paper describes the overarching framework of novel ongoing national Training and Mentoring Programme Melbourne University Sydney Queensland:Impact (MUSQ:Impact) for musculoskeletal researchers, including a description of how it was set up and established, and lessons learned from its implementation.

Results: The MUSQ:Impact programme spans four multidisciplinary musculoskeletal research teams across three universities in Australia, comprising 40-60 EMCR members.

The OARSI Joint Effort Initiative: Priorities for osteoarthritis management program implementation and research 2024-2028.

Objective: The Joint Effort Initiative (JEI) is an international collaboration of clinicians, researchers, and consumer organisations with a shared vision of improving the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify JEI's future priorities and guide direction.

Design: A two-part international survey to prioritise topics of importance to our membership and research stakeholders.

Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.

Checkpoint inhibitors have revolutionized cancer treatment, but resistance remains a significant clinical challenge. Myeloid cells within the tumor microenvironment can modulate checkpoint resistance by either supporting or suppressing adaptive immune responses. Using an anti-PD-1-resistant mouse melanoma model, we show that targeting the myeloid compartment via CD40 activation and CSF1R blockade in combination with anti-PD-1 results in complete tumor regression in a majority of mice.

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

Background: Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model.

Combined femoral and acetabular version and synovitis are associated with dGEMRIC scores in people with femoroacetabular impingement (FAI) syndrome.

This study sought to explore, in people with symptoms, signs and imaging findings of femoroacetabular impingement (FAI syndrome): (1) whether more severe labral damage, synovitis, bone marrow lesions, or subchondral cysts assessed on magnetic resonance imaging (MRI) were associated with poorer cartilage health, and (2) whether abnormal femoral, acetabular, and/or combined femoral and acetabular versions were associated with poorer cartilage health. This cross-sectional study used baseline data from the 50 participants with FAI syndrome in the Australian FASHIoN trial (ACTRN12615001177549) with available dGEMRIC scans. Cartilage health was measured using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score sampled at the chondrolabral junction on three midsagittal slices, at one acetabular and one femoral head region of interest on each slice, and MRI features were assessed using the Hip Osteoarthritis MRI Score.

Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA).

Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians.

Do patients with femoroacetabular impingement syndrome who undergo hip arthroscopy display improved alpha angle (magnetic resonance imaging) and radiographic hip morphology?

Aims: To compare (a) the change in radiological bony morphology between participants with femoroacetabular impingement (FAI) syndrome who underwent arthroscopic hip surgery compared to physiotherapist-led non-surgical care and (b) the change in radiological bony morphology between participants with FAI syndrome who underwent arthroscopic hip surgery involving cam resection or acetabular rim trimming or combined cam resection and acetabular rim trimming.

Methods: Maximum alpha angle measurements on magnetic resonance imaging and Hip Norm standardized hip measurements on radiographs were recorded at baseline and at 12 months postoperatively. One-way analysis of covariance and independent T tests were conducted between participants who underwent arthroscopic hip surgery and physiotherapist-led non-surgical care.

Moderators, Mediators, and Prognostic Indicators of Treatment With Hip Arthroscopy or Physical Therapy for Femoroacetabular Impingement Syndrome: Secondary Analyses From the Australian FASHIoN Trial.

Background: Although randomized controlled trials comparing hip arthroscopy with physical therapy for the treatment of femoroacetabular impingement (FAI) syndrome have emerged, no studies have investigated potential moderators or mediators of change in hip-related quality of life.

Purpose: To explore potential moderators, mediators, and prognostic indicators of the effect of hip arthroscopy and physical therapy on change in 33-item international Hip Outcome Tool (iHOT-33) score for FAI syndrome.

Study Design: Cohort study; Level of evidence, 2.

Implementation of Best-Evidence Osteoarthritis Care: Perspectives on Challenges for, and Opportunities From, Low and Middle-Income Countries.

The "Joint Effort Initiative" (JEI) is an international consortium of clinicians, researchers, and consumers under the auspices of the Osteoarthritis Research Society International (OARSI). The JEI was formed with a vision to improve the implementation of coordinated programs of best evidence osteoarthritis care globally. To better understand some of the issues around osteoarthritis care in low- and middle-income countries (LMICs), the JEI invited clinician researcher representatives from South Africa, Brazil, and Nepal to discuss their perspectives on challenges and opportunities to implementing best-evidence osteoarthritis care at the OARSI World Pre-Congress Workshop.

Automated volumetric and statistical shape assessment of cam-type morphology of the femoral head-neck region from clinical 3D magnetic resonance images.

Background: Femoroacetabular impingement (FAI) cam morphology is routinely assessed using manual measurements of two-dimensional (2D) alpha angles which are prone to high rater variability and do not provide direct three-dimensional (3D) data on these osseous formations. We present CamMorph, a fully automated 3D pipeline for segmentation, statistical shape assessment and measurement of cam volume, surface area and height from clinical magnetic resonance (MR) images of the hip in FAI patients.

Methods: The novel CamMorph pipeline involves two components: (I) accurate proximal femur segmentation generated by combining the 3D U-net to identify both global (region) and local (edge) features in clinical MR images and focused shape modelling to generate a 3D anatomical model for creating patient-specific proximal femur models; (II) patient-specific anatomical information from 3D focused shape modelling to simulate 'healthy' femoral bone models with cam-affected region constraints applied to the anterosuperior femoral head-neck region to quantify cam morphology in FAI patients.

Comparison of Walking Biomechanics After Physical Therapist-Led Care or Hip Arthroscopy for Femoroacetabular Impingement Syndrome: A Secondary Analysis From a Randomized Controlled Trial.

Background: Femoroacetabular impingement syndrome is characterized by chondrolabral damage and hip pain. The specific biomechanics used by people with femoroacetabular impingement syndrome during daily activities may exacerbate their symptoms. Femoroacetabular impingement syndrome can be treated nonoperatively or surgically; however, differential treatment effects on walking biomechanics have not been examined.