Background

Specifically designed control interventions can account for expectation effects in clinical trials. For the interpretation of efficacy trials of physical, psychological, and self-management interventions for people living with pain, the design, conduct, and reporting of control interventions is crucial.

Abstract

Abstract

In March 2020, the World Health Organisation declared the COVID-19 outbreak a pandemic. Multiple new guidelines were proposed and existing models of social, domestic and hospital care altered. Most healthcare systems were largely unprepared for this and this pandemic has tested their adaptability. This study is aimed at assessing the impact of covid-19 on the demographics, presentation and clinical management of patients with proximal femoral (hip) fractures.

This retrospective multi-centre cohort study compared all patients admitted with hip fractures, between 1^st March and 30th May 2019 (Group PC: Pre-Covid) with hip fracture patients admitted over the same time period during the pandemic in 2020 (Group C: Covid). The data was obtained from the hospitals' local and National Hip Fracture Databases. Mortality data was checked with the Office for National Statistics (ONS). Primary outcomes were time to theatre, in-patient length of stay and 30-day mortality.

580 patients were included (304 PC, 276 C). Patient Charlson comorbidity index and Nottingham Hip Fracture scores were broadly similar across the two cohorts. There was a significant reduction in percentage of total hip replacements in Group C (11% to 5%, p=0.006). There was an increase in conservative management in group C (1% to 5%, p=0.002). The time to theatre was significantly delayed in Group C (43.7 hours C versus 34.6 hours PC, p<0.001). Overall length of hospital stay was similar in both groups (16.6 days PC versus 15 days C, p=0.089). 30-day mortality rate in Group C was 9.8% compared to 8.2% in Group PC (p=0.431), but for covid (+) patients it was significantly higher at 38.2% versus 5.8% in covid (−) patients (p<0.001).

This is one of the largest multi-centre comparative cohort study in the literature to date, examining the impact of the covid-19 pandemic on the management of hip fracture patients. Whilst mortality rates were similar in both groups, covid patients were almost seven times more likely to die, reflecting the seriousness of the covid-19 infection and its sequelae in such elderly, vulnerable patients.

Bone tissue engineering is a promising strategy to treat the huge number of bone fractures caused by progressive population ageing and diseases i.e., osteoporosis. The bioactive and biomimetic materials design modulating cell behaviour can support healthy bone tissue regeneration. In this frame, type I collagen and hydroxyapatite (HA) have been often combined to produce biomimetic scaffolds. In addition, mesoporous bioactive glasses (MBGs) are known for their ability to promote the deposition of HA nanocrystals and their potential to incorporate and release therapeutic ions. Furthermore, the use of 3D printing technologies enables the effective design of scaffolds reproducing the natural bone architecture.

This study aims to design biomimetic and bioactive 3D printed scaffolds that mimic healthy bone tissue natural features in terms of chemical composition, topography and biochemical cues. Optimised collagenous hybrid systems will be processed by means of extrusion 3D printing technologies to obtain high resolution bone-like structures. Protocols of human co-cultures of osteoblasts and osteoclasts will be developed and used to test the 3D scaffolds.

Type I collagen has been combined with rod-like nano-HA and strontium containing MBGs (micro- and nano-sized particles) in order to obtain hybrid systems resembling the composition of native bone tissue. A comprehensive rheological study has been performed to investigate the potential use of the hybrid systems as biomaterial inks. Mesh-like structures have been obtained by means of extrusion-based technologies exploiting the freeform reversible embedding of suspended hydrogels (FRESH) approach. Different crosslinking methods have been tested to improve final constructs mechanical properties. Both crosslinked and non-crosslinked biomaterials were cultured with human osteoblasts and osteoclasts to assay the hybrid matrix biocompatibility as well as its influence on cell behaviour.

Homogeneous hybrid systems have been successfully developed and characterised, proving their suitability as biomaterial inks for 3D printing technologies. Mesh-like structures have been extruded in a thermo-reversible gelatine slurry, exploiting the sol-gel transition of the systems under physiological conditions. Covalent bonds between collagen molecules have been promoted by genipin treatment, leading to a significant increase in matrix strength and stability. The collagen methacrylation and the further UV-crosslinking are under investigation as alternative promising method to reinforce the 3D structure during the printing process. Biological tests showed the potential of the developed systems especially for genipin treated samples, with a significant adhesion of primary cells.

Collagenous hybrid systems proved their suitability for bioactive 3D printed structures design for bone tissue engineering. The multiple stimuli provided by the scaffold composition and structure will be investigated on both direct and indirect human osteoblasts and osteoclasts co-culture, according to the developed protocols.

INTRODUCTION

Quality monitoring is increasingly important to support and assure sustainability of the Orthopaedic practice. Many surgeons in a non-academic setting lack the resources to accurately monitor quality of care. Widespread use of electronic medical records (EMR) provides easier access to medical information and facilitates its analysis. However, manual review of EMRs is inefficient and costly. Artificial Intelligence (AI) software has allowed for development of automated search algorithms for extracting relevant complications from EMRs. We questioned whether an AI supported algorithm could be used to provide accurate feedback on the quality of care following Total Hip Arthroplasty (THA) in a high-volume, non-academic setting.

Aim

“Implant associated Staphylococcus aureus or S. epidermidis infections are often difficult to treat due to the formation of biofilms on prosthetic material. Biofilms are bacterial communities adhered to a surface with a self-made extracellular polymeric substance that surrounds resident bacteria. In contrast to planktonic bacteria, bacteria in a biofilm are in an adherent, dormant state and are insensitive to most antibiotics. In addition, bacteria in a biofilm are protected from phagocytic cells of the immune system. Therefore, complete surgical removal and replacement of the prosthetic implant is often necessary to treat this type of infections. Neutrophils play a crucial role in clearing bacterial pathogens. They recognize planktonic bacteria via immunoglobulin (Ig) and complement opsonisation. In this project, we aim to evaluate the role of IgG and complement in the recognition and clearance of staphylococcal biofilms by human neutrophils. Furthermore, we evaluate if monoclonal antibodies (mAbs) targeting biofilm structures can enhance recognition and clearance of staphylococcal biofilms by the human immune system.”

Background

The current use of a spherical prosthetic humeral head in total shoulder arthroplasty results in an imprecise restoration of the native geometry and improper placement of the center of rotation, maintained in a constant position, in comparison to the native head and regardless of glenoid component conformity.

A radially-mismatched spherical head to allow gleno-humeral translation is a trade-off that decreases the contact area on the glenoid component, which may cause glenoid component wear. This finding suggests that the use of a non-spherical head with a more conforming glenoid component may reduce the risk of glenoid component wear by allowing gleno-humeral translation while increasing the contact area.

A non-spherical prosthetic head more accurately replicates the head shape, rotational range of motion and gleno-humeral joint kinematics than a spherical prosthetic head, compared with the native humeral head. The combination of inversion of the bearing materials with the non-spherical configuration of the humeral head may thus decrease polyethylene wear.

Aim of the present study is to evaluate in vitro wear behaviour of an all-polyethylene elliptical humeral head component against a metallic glenoid component in an anatomic configuration.

Aim

Orthopedic implant related surgical site infection (SSI) is a severe complication which represents an important challenge concerning to its treatment. Therefore, gram-negative orthopedic infections have recently become a global concern.

Bone healing especially in elderly patients is a complex process with limited therapeutic options. In recent years the use of BMP2 for fracture healing is investigated extensively. However, for many applications superficial amounts of BMP2 were required for efficacy due to the absence of sustained release carriers and severe side effects have reported thereby limiting the use of BMP2. Here we present an alternative method based on the use of a combination of low molecular weight compounds, testosterone and alendronate, with established safety profiles in men. Moreover, in contrast to BMP2 which activates both osteoblasts and osteoclasts, this combination of drugs enhances osteoblast activity but simultaneously inhibits osteoclast activity resulting in a net effect of bone growth.

Human primary osteoblasts were obtained from bone of patients requiring knee prostheses and cultured in the presence of various concentrations testosterone with and without alendronate. Optimal concentrations were selected and used to stimulate 5×8 mm porcine bone biopsies for 4 weeks. Medium was exchanged regularly and ALP activity was determined. At endpoint biopsies were analyzed in a MicroCT (Bruker Skyscan 1076) to analyze bone volume (BV), trabecular thickness (Tb.Th) and tissue volume (TV). Bone strength was measured using Hounsfield (H10KT) test equipment.

The data obtained showed a significant and dose dependent increase in ALP activity of primary osteoblasts (day 7–10) indicating robust activation of osteoblast activity. Optimal and synergistic ALP activation was observed when treating cells with 15–375 nM testosterone in combination with 2 μM alendronate. Significant inhibition (75%) of osteoclast activity was observed by alendronate (2–10 μM) which was further enhanced by high testosterone levels. This concept was further tested in bovine bone biopsies cultured for 4 weeks in the presence of 75 nM testosterone and 2 μM alendronate. MicroCT analysis of the biopsies revealed a ± 40% increase in both bone volume (trabecular and cortical bone) and bone strength. Moreover bone mineral density was increased by 20% indicating increased mineralization of bone tissue.

Treatment of human primary osteoblasts or human or bovine bone explants with a combination of an androgen (testosterone) and a bisphosphonate (alendronate) significantly enhance bone growth and bone mineral density. Moreover, bone strength was increased indicating the formation of high quality bone tissue. These findings are the basis for the development of sustained release materials to be applied locally at the bone fracture site, which would allow for low amounts of the drugs and no systemic exposure. By encapsulating testosterone and alendronate in a biodegradable polymer coating, a sustained release up to 5 weeks can be achieved, and the loaded coating can be applied in combination with collagen membranes to improve bone healing or as a coating onto implants to improve osseo-integration.

Proliferation of synovial Mesenchymal Stromal/Stem Cells (MSCs) leads to synovial hyperplasia (SH) following Joint Surface Injury (JSI). Uncontrolled Yap activity causes tissue overgrowth due to modulation of MSC proliferation. We hypothesised that YAP plays a role in SH following JSI.

A spatiotemporal analysis of Yap expression was performed using the JSI model in C57Bl/6 mice. Synovial samples from patients were similarly analysed. Gdf5-Cre;Yap1fl/fl;Tom mice were created to determine the effect YAP1 knockout in Gdf5 lineage cells on SH after JSI.

In patients, Yap expression was upregulated in activated synovium, including a subset of CD55 positive fibroblast-like synoviocytes in the synovial lining (SL). Cells staining positive for the proliferation marker Ki67 expressed active YAP.

In mice, Yap was highly expressed in injured knee joint synovium compared to controls. Yap mRNA levels at 2 (p<0.05) and 8 days (p<0.001) after injury were increased.

Conditional Yap1 knockout in Gdf5 progeny cells prevented hyperplasia of synovial lining (SL) after JSI. Cellularity was significantly decreased in the SL but not in the sub-lining of injured Yap1 knockout- compared to control mice. The percentage of cells in synovium that were Tom+ increased in response to JSI in control and haplo-insufficient but not in YAP1 knockout mice (p<0.05).

Modulation of YAP and proliferation of MSCs in the synovium after JSI provides a system to study the role of SH after trauma in re-establishing joint homeostasis and is a potential novel therapeutic target for the treatment of post traumatic OA.

Introduction

Reverse shoulder prosthesis has been developed to treat the clinical and pathological condition noted as cuff tear arthropathy (CTA).

The current models of reverse shoulder arthroplasty (RSA) expose the procedure to the risk of scapular notching, possibly leading to loosening of the glenoid.

Introduction:

Reverse shoulder arthroplasty (RSA) is a reasonable treatment modality in patients with Cuff Tear Arthropaty and massive irreparable cuff tears. RSA has been shown to increase patient function and decrease pain. The aim of this study is to evaluate the clinical and radiographic results of a 44 polyethylene glenosphere.

Background:

Different surgical approaches have been proposed for the treatment of chondral lesions. However surgical management of osteochondral defects of the knee joint involving subchondral bone are still under debate.

Purpose: The purpose of this retrospective studies is to evaluate the real effectiveness, with clinical and radiologic evalutation, of the eccentric glenosphere and also how a correct position can prevent the scapular notching.

Material and Methods: We inplanted in 18 patients, with eccentric arthopaty, a 36 mm eccentric glenoshere.24 months’ clinical and radiographic follow up. All patient were assessed preoperatively and postoperatively with the Constant Score. In the post-operative radiographic control we have taken in consideration: the presence of notching, psna (prosthesis-scapular neck angle), pgrd (peg glenoid distance), glenoid inclination, craniocaudal position of the glenosphere in relation to the glenoid.

Results: The ROM increased in all level. All of the 18 shoulder had no notching. The craniocaudal position of the glenosphere in relation to the glenoid is 4,3 mm. The PSNA was 92° and the PGRD was 21.2.

Conclusion: The inferior scapular notching is the most important complicance of reverse prosthesis. The results of our study indicate that : the correct positioning of the metal back, at the center of the glenoid (better biomechanics stability), without overhang and with eccentric glenosphere, permits to lower the center of rotation of 4 mm avoiding the notch and so increasing the adduction and abduction range of motion.

Purpose: Deciding how to allocate scarce surgical resources is a worldwide issue. These decisions can be especially difficult when considering procedures aimed primarily at improving functional quality of life, such as lower extremity joint replacement (LEJR) surgery, and those procedures that can be perceived primarily as life preserving but should also have an impact on physical function, such as coronary artery bypass graft (CABG) surgery. A comparison of the functional outcomes of these two different procedures may provide further evidence to guide resource allocation decisions. The purpose of this study is to compare patient-reported functional outcomes following CABG and LEJR surgery using standardized, validated outcome metrics.

Method: A retrospective review of prospectively collected pre and post-operative health related quality of life (SF-36) measures from patients undergoing elective CABG and elective LEJR surgery in an academic surgical center. The sample included 112 CABG patients who were matched with LEJR patients based on gender and age.

Results: The mean age in the CABG group was 63 years, in the LEJR group 64 years. Seventy eight percent (78%) of the patients were male. Pre-operatively, CABG patients reported statistically higher (p< 0.05) Physical Functioning, less Bodily Pain, and superior Physical Component summary SF-36 scores compared to the LEJR group. However, their pre-operative General Health scores were statistically lower. Surgery resulted in a general improvement in all SF-36 scales and summary scores for all patients, with statistically significant improvements in Bodily Pain and General Health Scores occurring in both groups. Interestingly, the improvement in Bodily Pain score was greater for the LEJR group than the CABG group, whereas the improvement in General Health Score was greater in the CABG group. However the pre-operative pattern of statistically better Physical Functioning, Bodily Pain and Physical Component summary SF-36 scores in the CABG group, and superior General Health scores in the LEJR group remained following surgery.

Conclusion: It appears that, despite being matched for age and gender, significant pre-operative general health differences exist between CABG and LEJR patients that persist post-operatively. While surgery does result in significant improvements for both groups, CABG patients enjoy greater improvement in General Health scores while LEJR patients benefit from greater improvements in Bodily Pain scores. Further research is currently underway to examine how these differences are reflected in disease-specific scores and in health care resource utilization.

Current 5-year survival after complete resection of pulmonary metastases is ≈ 30%, and many patients develop pulmonary recurrences. Obviously new treatment options are needed for this indication. Isolated lung perfusion (ILuP) is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. Recently, a phase I trial of ILuP combining 45 mg melphalan followed by pulmonary metastasectomy for resectable lung metastases proved to be feasible and safe.

The current 3-center phase II study (including University Hospital Antwerp/P. van Schil and Anthonius Hospital Nieuwegein/F. Schramel) allows patients with resectable lung metastases from colorectal cancer, soft tissue- and osteosarcoma to be treated with ILuP prior to metastasecomy.

At Leiden University Medical Center we treated 8 patients: 4 with colorectal cancer (age 54–59 y), 2 osteosarcoma (19–20 y), 1 sarcoma NOS of bone (38 y) and 1 sarcoma NOS (56 y) of soft tissue. The number of metastases was 1–2 and one patient had resection of 9 metastases. The procedure was uncomplicated in 7 cases and 1 patient had reversible pulmonary edema. Hospital admission duration was 6–8 days in the uncomplicated group and 14 days in the one patient with a complication. No long term toxicity was observed with extensive follow-up including lung function tests. With a median follow-up of 7 months (range 2–16), only the patient with 9 metastases had a recurrence and died of disease.

Our single center prelimininary data show that ILuP is feasible and does not lead to irreversible or severe toxicity. Compared to retrospective data with metastasectomy alone, perfusion did not add toxicity. Follow-up is too short to draw any conclusions on efficacy.

Published experimental data on BMP-7(OP-1), carried by collagen type 1 (Osigraft), related to reconstructive surgery attest that: it accelerates and improves the incorporation of strut allograft; the combination of OP-1 with auto or allograft results in an improvement of critical size defect healing from radiological, histological and mechanical perspective.

In human revision hip surgery, OP-1 has been used with morcellized allograft, proximal femoral allograft and bulk femoral head allograft for acetabular or femoral reconstruction: a faster and more evident new bone formation as well as a faster incorporation of grafts has been shown compared to what expected without OP-1 usage.

Even if OP-1 usage in hip surgery is not approved by regulatory agencies, because of lack of randomised clinical studies, we decided to use it in patients with serious acetabular defects (II/III GIR).

In our experience, we treated eight patients with OP1, in conjunction with allografts. Clinical, radiographic and densitometric analysis has been done at 3, 6 and 12 months.

Preliminary densitometric results show that the quantity and features of new formed bone are superimposable to natural bone.

High Tibial Osteotomy (HTO) is an established treatment for unicompartmental osteoarthritis of the knee with malalignment. The classic procedure for correcting varus deformity is the lateral closed wedge osteotomy of the tibia with osteotomy of the fibula. The disadvantages of this technique are well known. Open wedge osteotomy from the medial sideeliminates the risk of compartment syndrome and peroneal nerve injuries. A new fixation device (TomoFix(tm)) with an adapted surgical technique allows stable fixation of the osteotomy without the need to fill the osteotomy gap with bone grafts. In a prospective study, 92 consecutive cases were treated with this procedure. Bony healing with remodelling of the medial and posterior cortical bone was observed. Full weight-bearing was possible ten weeks after surgery. There were no implant failures. Complications included one delayed union, two revarisations and one deep infection. Keywords: High Tibial Osteotomy (HTO), openwedge osteotomy, TomoFix(tm) plate, medial osteoarthritis, varus knee

Study Design: To design and test a new questionnaire to assess depression and other mood states.

Summary of Background Data: Measurement of depression and of other mood states in pain patients has been criticised in recent years on the grounds that most questionnaires were not developed in pain populations and suffer from criterion contamination by somatic items. In addition, there is no accepted measurement for positive emotions which are more than the absence of depression.

Objective: To develop a reliable and brief tool to assess mood in pain patients.

Method: Non-somatic items concerning depression, anxiety and positive outlook were extracted using exploratory factor analysis from commonly used instruments (Beck Depression Inventory and Hospital Anxiety and Depression Scale) completed by over 900 chronic pain patients. Confirmatory factor analysis was used to test the internal structure of the final item set. Items were then reworded and presented as a new questionnaire (the Depression, Anxiety and Positive Outlook Scale: DAPOS) to two new samples: patients attending pain management and patients attending osteopathy. The new questionnaire was compared with several well-known questionnaires (SF-36, BDI, PCS). The structure was calibrated and tested using confirmatory factor analysis on both samples. Finally, a sub-set of patients carried out a sorting task to test for face validity.

Results and conclusion: The DAPOS performed well, indicating that it is a reliable measure of the three mood states with good initial evidence of validity in these samples.