Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that
Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular
Low back pain is more common in women than men, yet most studies of intervertebral disc (IVD) degeneration do not address
As treatments of knee osteoarthrosis are continually refined, increasingly sophisticated methods of evaluating their biomechanical function are required. Whilst TKA shows good preoperative pain relief and survivorship, functional outcomes are sub-optimal, and research focus has shifted towards their improvement. Restoration of physiological function is a common design goal that relies on clear, detailed descriptions of native biomechanics. Historical simplifications of true biomechanisms, for example sagittal plane approximation of knee kinematics, are becoming progressively less suitable for evaluation of new technologies. The patellar tendon moment arm (PTMA) is an example of such a metric of knee function that usefully informs design of knee arthroplasty but is not fully understood, in part due to limitations in its measurement. This research optimized PTMA measurement and identified the influence of knee size and sex on its variation. The PTMA about the instantaneous helical axis was calculated from optical tracked positional data. A fabricated knee model facilitated calculation optimization, comparing four data smoothing techniques (raw, Butterworth filtering, generalized cross-validated cubic spline-interpolation and combined filtering/interpolation). The PTMA was then measured for 24 fresh-frozen cadaveric knees, under physiologically based loading and extension rates.
Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and
Neoangiogenesis drives the replacement of mineralised cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL. The Heparan sulfate proteoglycan Syndecan-1 (Sdc1) plays a role in the interaction of osteoclasts and osteoblasts and the development of blood vessels. We expected Sdc1 to have an influence on bone structure and vessel development. Therefore, bone structure and angiogenesis at the growth plate in mice was compared and the influence of Syndecan-1 deficiency was characterised. Animals: Femura of male and female C57BL/6 WT (5♀, 6♂) and Sdc1-/- (9♀, 5♂) mice were used for native bone analysis at 4 month age. Histology: Bone structure was analysed using microCT scans with a resolution of 9µm. Vascularisation was visualised using an anti-Endomucin antibody in 80µm thick cryosections. In vitro angiogenesis: Bone marrow isolates were used to generate endothelial progenitor cells by sequential cultivation on fibronectin. Microvessel development was analysed 4h after plating on matrigel. Bone structure in male Sdc1 deficient mice was significantly reduced compare to male WT, whereas female mice of both genotypes did not differ. Sdc1 deficient mice at the age of 4 month showed a high decrease in the number of vessel bulbs at the chondro-osseous border (growth plate) compared to WT mice. However, no
Introduction and Objective. Klinefelter Syndrome (KS, karyotype 47,XXY) is the most frequent chromosomal aneuploidy in males, as well as the most common cause of infertility in men. Patients suffer from a lack of testosterone, i.e. hypergonadotropic hypogonadism provoking infertility, but KS men also show an increased predisposition to osteoporosis and a higher risk of bone fracture. In a mouse model for human KS, bone analysis of adult mice revealed a decrease in bone mass that could not be rescued by testosterone replacement, suggesting a gene dosage effect originating from the supernumerary X-chromosome on bone metabolism. Usually, X chromosome inactivation (XCI) compensates for the dosage imbalance of X-chromosomal genes between sexes. Some studies suggested that expression of genes that escape silencing of the supernumerary X-chromosome (e.g. androgen receptor) has an impact on
Distal radius fractures are the most common upper extremity injury, and are increasingly being treated surgically with pre-contoured volar-locking plates. These plates are favored for their low-profile template while allowing for rigid anatomic fixation of distal radius fractures. The geometry of the distal radius is extremely complex, and little evidence within the medical literature suggests that current implant designs are anatomically accurate. The main objective of this study is to determine if anatomic alignment of the distal radii corresponds accurately with modern volar-locking plate designs. Additionally, this study will examine sex-linked differences in morphology of the distal radius. Segmented CT models of ten female cadaver (mean age, 88.7 ± 4.57 years, range, 82 – 97) arms, and ten male cadaver (mean age, 86 ± 3.59 years, range, 81 – 91) arms were created. Micro CT models were obtained for the DePuy Synthes 2.4mm Extra-articular (EA) Volar Distal Radius Plate (4-hole and 5-hole head), and 2.4mm LCP Volar Column (VC) Distal Radius Plate (8-hole and 9-hole head). Plates were placed onto the distal radii models in a 3D visualization software by a fellowship-trained orthopaedic hand surgeon. The percent contact, volar cortical angle (VCA), border and overlap of the watershed line (WSL) were measured. Both sexes showed an increase in the average VCA measure from medial to lateral columns which was statistically significant. Female VCA ranged from 28 – 36 degrees, and 38 – 45 degrees for males. WSL overlap ranged from 0 – 34.7629% for all specimens without any statistical significance. The average border distance for females was 2.58571 mm, compared to 3.52411 mm for males, with EA plates having a larger border than VC plates. The border distances had statistically significant differences between the plate types, and was approaching significance between sexes. Lastly, a maximum percent contact of 21.966 % was observed in specimen F4 at a 0.3 mm threshold. No statistical significance between plate or sex populations was observed. This study investigated the incoherency between the volar cortical angle of the distal radius, and the pre-contoured angle of volar locking plates. It was hypothesized that if the VCA measures between plate and bone were unequal then there would be an increase in watershed line overlap, and decrease in percent contact between the surfaces. Our results agreed with literature, indicating that the VCA of bone was larger than that of the EA and VC pre-contoured plates examined in this study. With distal radius fracture incidences and prevalence on the rise for elderly female patients, it is a necessity that volar locking plates be re-designed to factor in anatomical features of individual patients with a particular focus on
Introduction. For anatomical reconstruction in shoulder arthroplasty, it is important to understand normal glenohumeral geometry. Unfortunately, however, the details of the glenohumeral joint in Asian populations have not been sufficiently evaluated. There is a racial difference in body size, and this difference probably results in a difference in glenohumeral size. The purpose of this study was to evaluate three-dimensional geometry of the glenohumeral joint in the normal Asian population and to clarify its morphologic features. Methods. Anthropometric analysis of the glenohumeral joint was performed using computed tomography scans of 160 normal shoulders from healthy volunteers in age from 20 to 40 years. Using OsiriX MD, Geomagic Studio, and AVIZO software, the dimensions of humeral head width, humeral head diameter, glenoid height, glenoid width, and glenoid diameter were analyzed three-dimensionally (Figure 1). In diameter analyses, the humeral head was assumed to be a sphere and the glenoid was to fit a sphere (Figure 2–3).
Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.Aims
Methods
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.Aims
Methods
To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.Aims
Methods
As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.Aims
Methods
The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD. This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression.Aims
Methods
Aim. This study aimed to evaluate the impact on length of hospital stay from dedicated infectious diseases input for orthopaedic infection patients compared to sporadic infection specialist input. Method. We conducted an observational cohort study of 157 adults with orthopaedic infections at a teaching hospital in the UK. The orthopaedic infections included were: osteomyelitis, septic arthritis, infected metalwork and prosthetic joint infections, and adults were aged 18 years or more. Prior to August 2016, advice on orthopaedic infection patients was adhoc with input principally from the on-call infectious diseases registrar and phone calls to microbiology whereas after August 2016 these patients received regular input from dedicated infectious diseases doctor(s). The dedicated input involved bedside reviews, medical management, correct antimicrobial prescribing, managing adverse drug reactions, increased use of outpatient parenteral antimicrobial therapy (OPAT) services especially self-administration of intravenous antibiotics and shared decision-making for treatment failure, whilst remaining under orthopaedic team care. Orthopaedic patients operated on for management of their infection between 29/8/16 and 15/3/17 were prospectively identified and orthopaedic operation records were used to retrospectively identified patients between 29/8/15 and 15/3/16. The length of stay was compared between the 2 groups. Results. There were 83 patients in the dedicated infectious diseases input group (dedicated group) and 74 patients in the sporadic infection specialist input group (sporadic group). The dedicated group were significantly younger: median 58 years versus 69years (p<0.001), and there was a trend to significant differences in the breakdown of diagnosis (p=0.06), but no significant
Background. Total Hip Arthroplasty (THA) has long been the standard treatment for cases in which non-surgical alternatives have failed to improve pain and function in hip osteoarthritis (OA) patients. Outcomes from THA have improved over time with better surgical techniques and improved implant designs. While conventional neck-sacrificing implants have been associated with favorable outcomes, there is evidence to suggest biomechanical advantages of newer, femoral neck-preserving short-stem implants, including the Corin MiniHip. However, there is a still a gap of knowledge regarding the potential benefits of the MiniHip stem over conventional neck-sacrificing stems in regards to patient-reported outcomes (PROs). In this study, we investigated the differences between a neck-sacrificing stem design and neck-preserving short-stem design (MiniHip, Corin Inc.) arthroplasty concerning PROs, and considering the known features of the short stem design, we hypothesized that MiniHip THA would be associated with improved PROs in comparison to a neck-sacrificing implant system. We further sought to investigate gender effects related to MiniHip or conventional stem surgery. Methods. Neck-sacrificing implant patients (n=90, age 57±7.9 years, female=58, male=32) and a matched (matching criteria: follow-up period, BMI, age) cohort group of MiniHip patients (n=105, age 55.16±9.88 years, female: 25, male: 80) reported both pre-operative and post-operative Hip disability and Osteoarthritis Outcome Scores (HOOS) at a minimum interval of 6 months post-operatively and up to three years postoperatively. We applied MANCOVA analysis to compare patient-reported outcome subscores from each group using follow-up period as a covariate and employing gender as an additional grouping factor to evaluate gender effects. Statistical significance was set at α=0.05 and Bonferroni corrections were applied to account for multiple comparisons. Results. There was a main effect of time, showing that all HOOS subscores of both groups increased significantly after surgery (p<0.001). There was a main effect of surgery for subscores Symptoms (p=0.038), ADL (p=0.046), and Sports and Recreation (p=0.039). There was a gender effect only for the subscore Symptoms (p=0.007). There were significant time by surgery interactions for HOOS subscores Symptoms (p=0.002), Pain (p=.009), Sports and Recreation (p=0.004), and QOL (p<0.001) subscores. We also observed a significant time by gender interaction effect for all HOOS subscores (p<0.001). Discussion. The interaction effects regarding most HOOS subscores and surgery/implant type indicate an advantage of MiniHip surgery regarding post-operative reported outcomes. The observed results may be due to previously described improved physiological loading and native hip structure preservation with neck-preserving short-stem designs. While longer-term studies are required for further investigation, evidence suggests the MiniHip may provide a significant benefit to primary THA patients. The additional gender/time interaction effect observed in our study highlights the necessity to consider potential
The frequency of severe femoral retroversion is unclear in patients with femoroacetabular impingement (FAI). This study aimed to investigate mean femoral version (FV), the frequency of absolute femoral retroversion, and the combination of decreased FV and acetabular retroversion (AR) in symptomatic patients with FAI subtypes. A retrospective institutional review board-approved observational study was performed with 333 symptomatic patients (384 hips) with hip pain due to FAI evaluated for hip preservation surgery. Overall, 142 patients (165 hips) had cam-type FAI, while 118 patients (137 hips) had mixed-type FAI. The allocation to each subgroup was based on reference values calculated on anteroposterior radiographs. CT/MRI-based measurement of FV (Murphy method) and AV were retrospectively compared among five FAI subgroups. Frequency of decreased FV < 10°, severely decreased FV < 5°, and absolute femoral retroversion (FV < 0°) was analyzed.Aims
Methods
Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old Aims
Methods
Background. Glenoid baseplate fixation for reverse shoulder arthroplasty relies on the presence of sufficient bone stock and quality. Glenoid bone may be deficient in cases of primary erosions or due to bone loss in the setting of revision arthroplasty. In such cases, the best available bone for primary baseplate fixation usually lies within the three columns of the scapula. The purpose of this study was to characterise the relationship of the three columns of the scapula independent of glenoid anatomy and to establish the differences between male and female scapular anatomy. Methods. Fifty cadaveric scapulae (25 male, 25 female) were analysed using CT-based imaging software. The surface geometries of the coracoid, scapular spine and inferior scapular column were delineated in the sagittal plane. A linear best-fit line was drawn to establish the long axis of each column independent of the glenoid. The width of the glenoid was measured and points marked at the midpoint of each measurement. A best-fit line starting at the supra glenoid tubercle passing through the midpoints was chosen as the superior inferior (SI) axis of the glenoid. An orthogonal plane to the scapular plane was developed parallel to the glenoid face. The axis representing each of the three columns of the scapula and the SI axis of the glenoid, were projected onto this plane. The relationship between each column was analysed with respect to each other and with respect to the SI glenoid axis. Thus, measurements obtained gave the relationships of the three columns of the scapula (independent of the glenoid) and their relationships to the long axis of the glenoid (dependant on the glenoid). Comparisons were made between males and females using the independent t-tests. Results. The mean angle between the scapular spine and the coracoid column was 93±13° with no significant difference between males (91±15°) and females (95±10°) (p=0.29). The angle between the inferior scapular column and the scapular spine was 6.5° greater (p=0.03) in females (134±10°) than in males (128±11°). Similarly, the angle between the inferior scapular column and the coracoid column was 11° greater (p=0.009) in males (141±15°) than in females (130±12°). No significant