This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.Aims
Methods
As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics. A systematic review was conducted by searching Medline, Emcare, Embase, PsycINFO, OrthoSearch, and the Cochrane Library in November 2022. The Preferred Reporting Items for Systematic Reviews and Meta Analysis were adhered to. Original research papers that focused on pregnancy and/or parenthood within orthopaedic surgery were included for review.Aims
Methods
The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS.Aims
Methods
Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms. Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment. CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies). CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.
We have previously reported an injectable hydrogel (NPgel), which could deliver patients own stem cells, via small bore needles, decreasing damage to the annulus fibrosus. NPgel drives differentiation to NP cells and can inhibit the degenerate niche. However, clinical success of NPgel is dependent on the capacity to inject NPgel into naturally degenerate human discs, restore mechanical function to the IVD, prevent extrusion during loading and induce regeneration. This study assessed injectability of NPgel into human IVD, influence on mechanical properties, regeneration ability in an Cadaveric human discs were used to calculate disc height and to determine Youngs Modulus during simulated walking pre and post injection of NPgel, extrusion testing performed. Whole human IVDs were injected with NPgel +/− human BMPCs and maintained in culture under physiological loading regime for 4 weeks. Pre and post culture MRI imaging and in line biomechanical characteristics determined. Histology and immunochemistry performed for anabolic and catabolic factors.Background
Methodology
Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.Aims
Methods
There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA. We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs.Aims
Methods
The primary aim of this study was to assess if traumatic triangular fibrocartilage complex (TFCC) tears can be treated successfully with immobilization alone. Our secondary aims were to identify clinical factors that may predict a poor prognosis. This was a retrospective analysis of 89 wrists in 88 patients between January 2015 and January 2019. All patients were managed conservatively initially with either a short-arm or above-elbow custom-moulded thermoplastic splint for six weeks. Outcome measures recorded included a visual analogue scale for pain, Patient-Rated Wrist Evaluation, Disabilities of the Arm, Shoulder and Hand score, and the modified Mayo Wrist Score (MMWS). Patients were considered to have had a poor outcome if their final MMWS was less than 80 points, or if they required eventual surgical intervention. Univariate and logistic regression analyses were used to identify independent predictors for a poor outcome.Aims
Methods
To analyze the short-term outcome after medial open-wedge high tibial osteotomy with a 3D-printing technology in early medial keen osteoarthritis and varus malalignment. 32 knees(28 cases) of mOWHTO (fixation with an angular-stable TomoFix implant(Synthes)) with a 3D-printing technology combined with arhtroscopy were prospectively surveyed with regard to functional outcome(Hospital for special knee score [HSS] score). Pre- and postoperative tibial bone varus angle (TBVA), mechanical medial proximal tibial angle (MPTA), and alignment were analyzed with regard to the result.Objective
Design and Method
Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin.Aims
Methods
Quality measures play a substantial role in the Centers for Medicare and Medicaid Services' hospital payment and public reporting programs. The purpose of this study was to assess whether public measurement of total hip and knee arthroplasty risk-standardized readmission (RSRRs) and complication rates (RSCRs) was temporally associated with decreasing rates of adverse outcomes among Medicare beneficiaries. We evaluated annual trends in hospital-level risk-standardized complication and readmission rates in the fiscal years 2010–11 and 2016–17 for patients undergoing hospital-based inpatient hip/knee replacement procedures. We calculated hospital-level rates using the same measures and methodology used in public reporting. We examined annual trends in the distribution of hospital-level outcomes through density plots (similar to histograms).Introduction
Methods
The goal of closed reduction (CR) in the treatment of developmental dysplasia of the hip (DDH) is to achieve and maintain concentricity of the femoral head in the acetabulum. However, concentric reduction is not immediately attainable in all hips and it remains controversial to what degree a non-concentric reduction is acceptable. This prospective study is aimed at investigating the dynamic evolution of the hip joint space after CR in DDH using MRI. A consecutive series of patients with DDH who underwent CR since March 2014 were studied. Once the safety and stability were deemed adequate intraoperatively, reduction was accepted regardless of concentricity. Concentricity was defined when the superior joint space (SJS) and medial joint space (MJS) were both less than 2 mm, based on MRI. A total of 30 children, six boys and 24 girls, involving 35 hips, were recruited for the study. The mean age at CR was 13.7 months (3.5 to 27.6) and the mean follow-up was 49.5 months (approximately four years) (37 to 60). The joint space was evaluated along with the interval between the inverted and everted limbus.Aims
Methods
Different criteria for assessing the reduction quality of trochanteric fractures have been reported. The Baumgaertner reduction quality criteria (BRQC) are relatively common and the Chang reduction quality criteria (CRQC) are relatively new. The objectives of the current study were to compare the reliability of the BRQC and CRQC in predicting mechanical complications and to investigate the clinical implications of the CRQC. A total of 168 patients were assessed in a retrospective observational study. Clinical information including age, sex, fracture side, American Society of Anesthesiologists (ASA) classification, tip-apex distance (TAD), fracture classification, reduction quality, blade position, BRQC, CRQC, bone quality, and the occurrence of mechanical complications were used in the statistical analysis.Objectives
Methods
Hoffa fractures are rare, intra-articular fractures of the femoral condyle in the coronal plane and involving the weight-bearing surface of the distal femur. Surgical fixation is warranted to achieve stability, early mobilisation and satisfactory knee function. We describe a unique type of Hoffa fracture in the coronal plane with sagittal split and intra-articular comminution. There is scant evidence in current literature with regards to surgical approaches, techniques and implants. We report of our case with a review of the literature. A 40 year old male motorcyclist was involved in a high speed road traffic collision. X-rays confirmed displaced unicondylar fracture of the lateral femoral condyle. CT showed sagittal split of the Hoffa fragment and intra-articular comminution. MRI showed partial rupture of the anterior cruciate ligament. The patient underwent definitive surgical treatment via a midline skin incision and lateral parapatellar approach using cannulated screws, headless compression screws and anti-glide plate. Weightbearing was commenced at 8 weeks. Arthroscopy and adhesiolysis was performed at 12 weeks to improve range of motion. The patient was discharged at one year with a pain-free, functional knee.Introduction
Case report
The anterior-posterior (AP) pelvis radiograph is crucial for diagnosis of neck of femur (NOF) fractures, especially as this is one of the commonest fractures in the elderly population. Anecdotally we found that initial AP pelvis radiographs for these suspected fractures did not always exhibit the bones sufficiently. Repeat radiographs were needed, leading to delays in diagnosis, treatment, and repeated radiation exposure. Missed diagnoses can have significant consequences for this patient group. We assessed how many initial AP pelvis radiographs taken for suspected NOF fracture fitted criteria for adequate diagnostic imaging. A retrospective study was carried out assessing the initial AP pelvis radiograph done for each patient presenting to our dedicated NOF unit with suspected NOF fracture for 1st June – 31st July 2014. European Guidelines for Diagnostic Imaging were used as the benchmark. Each radiograph was scored out of six, one for each criteria fulfilled. Guidelines deemed images scoring ≤3 as inadequate.Background
Methods
Focal resurfacing can treat localised articular damage of the knee not appropriate for arthroplasty or biological repair. Independent results on these implants are limited. We previously published early results showing significantly improved Knee Injury & Osteoarthritis Outcome Score (KOOS4) without complication or re-operation, demonstrating this system gives good analgesia and functional improvement in selected patients. We present long-term follow-up of these patients. We prospectively evaluated medium- to long-term results in patients with localised, full-thickness articular cartilage defects of the knee undergoing HemiCAP resurfacing. All procedures were performed by one consultant surgeon. Post-operative rehabilitation was standardised. Outcome measures were KOOS4 score, visual analogue score (VAS), Kellgren and Lawrence arthritis grade, and re-operation rates.Background
Methods
Radial head fractures are the commonest fractures involving the elbow. The goals of treatment are to restore stability, preserve motion, and maintain the relative length of the radius. Fortunately, most simple uncomplicated fractures can be treated non-operatively. Choosing between fixation and radial head replacement for comminuted fractures remains difficult. Excision of radial head fractures is not an ideal option in unstable elbow injuries. The purpose of this systematic review was to search for and critically appraise articles directly comparing functional outcomes and complications for fixation (open reduction internal fixation, ORIF) versus arthroplasty for comminuted radial head fractures (Mason type 3) in adults. A comprehensive search of Medline, Embase and Cochrane databases using specific search terms and limits was conducted. Strict eligibility criteria were applied to stringently screen resultant articles. Three comparative studies were identified and reviewed.Background
Method
Osteonecrosis of the femoral head is a complex pathologic process with many aetiological factors. Factors most often mentioned in the literature are mechanical disruption (hip trauma or surgery), steroid use, smoking, haemoglobinopathies and hyperlipidaemia.1 Our case depicts a rare association of crack cocaine related to osteonecrosis of the femoral head which has never been reported in the available literature. Case Report: A 32 year old man was referred to our Orthopaedic clinic with right hip pain. He had a 9 pack-year history of cigarette smoking and had also smoked crack cocaine between ages 20 to 28; shortly after this the hip pain started. He denied antecedent injury. He had undergone a steroid injection into his right ankle abroad for swelling one year before referral, which was after onset of hip pain. MRI of his hip previously performed abroad had been normal. The patient had an indoor job and was otherwise fit and well. On examination he had reduced of movement in his right hip with 5–10 degrees of fixed flexion deformity. Plain radiography demonstrated cyst formation and sclerosis of both femoral heads. Repeat MRI confirmed bilateral osteonecrosis, worse on the right with risk of head collapse. The patient underwent bilateral core decompressions. Subsequent follow-up demonstrated a mobile patient with no need for arthroplasty and he was discharged after two years. Osteonecrosis is caused by the coagulation of the intra-osseous microcirculation leading to thrombosis formation and eventual reduction in osseous blood supply. Steroid use is associated with increased risk of osteonecrosis to the femoral head, however in these cases the patients often undergo either direct local or systemic infiltration of steroid. In this case steroid was administered after symptoms began to a far distant site and therefore cannot be the cause. Cigarette smoking is also known to cause osteonecrosis. Our patient had smoked cigarettes for fourteen years without problems, and it was after he ceased to smoke crack cocaine that his symptoms began. Cocaine blocks voltage-gated sodium-channels causing vasospasm. It is known to cause nasal and facial bone osteonecrosis due to its common intranasal method of delivery. We postulate that in this case crack cocaine was a synergistic factor towards development of femoral head osteonecrosis.
We performed a systematic review to compare outcomes of cemented versus uncemented trapezio-metacarpal joint (TMCJ) replacement for treatment of base-of-thumb arthritis. We assessed improvements in pain and function, range of movement (ROM), strength, complications and need for revision surgery. A thorough literature search was performed. A total of 481 studies were identified from the literature search (179 Medline, 253 Embase, 27 CINAHL, 22 Cochrane). Of 43 relevant titles 28 were selected for full-text review after assessment of the abstracts. Duplicate studies were removed. 18 studies met inclusion criteria on full-text review. All studies were of level IV evidence. There were no randomised controlled trials or meta-analyses. The studies were critically appraised using a validated scoring system. Most studies reported good outcomes for pain and strength, and functional outcome was comparable for both groups. ROM was generally improved for both prosthetic types, however statistical calculation was lacking in many studies. Trapezial component loosening was the main problem for both cemented and uncemented prostheses, however radiological loosening did not necessarily correlate with implant failure. This systematic review has found that both cemented and uncemented replacements generally give good outcomes for the treatment of TMCJ arthritis, however young, male, patients with manual occupations and with disease in the dominant hand and patients with poor trapezial bone stock appear to be at higher risk for implant failure due to cup loosening. We recommend the construction of a joint registry to record implantation and revision rates.
There has been evidence of association between femoral shaft fractures and prolonged bisphosphonate therapy. We present a case series of bisphosphonate-associated fractures and invaluable lessons we have learnt. Over the last three years at our unit we have collected a case series of eight patients who have had atypical femoral fractures whilst on bisphosphonate therapy. We present illustrative cases, a summary of key findings, and invaluable lessons we have learnt. There was a long period of prodromal pain for two years before incomplete fractures developed. We speculate this is a warning sign of impending fracture. This may have been prevented with screening. Between incomplete fracture and complete fracture there was a short window of one month. Five patients presented with complete fracture, and three with thigh pain +/- evidence of incomplete fracture. Of the latter group all but one went on to develop complete fractures. The one patient who did not progress died six years after diagnosis. Of those five patients who presented with initial complete fracture, three patients recall thigh pain before fracture on further questioning. Despite being diaphyseal femoral fractures, there is a higher risk of neck of femur fractures in this patient cohort (both patients with initial interlocked nails subsequently developed neck of femur fractures soon after and were revised to cephalomedullary nails). Excluding one death from unrelated cause, only one patient has signs of complete fracture healing. All other patients are still receiving follow-up (mean 490 days). Three patients reported bilateral symptoms (pain). Two had had bilateral symptoms for one year. Both had visible incomplete fractures on further radiographic scrutiny; one underwent prophylactic cephalomedullary nailing, one was managed with active surveillance. We suggest that improved pain and radiographic changes of cortical healing may be misleading and should not be relied upon. Cephalomedullary nailing is the treatment of choice in these fractures due to higher risk of neck of femur fractures in this cohort. We suggest prompt prophylactic cephalomedullary nailing when radiographic incomplete fractures are identified due to a short window before progression to complete fracture, and the need to consider contralateral prophylactic nailing in patients describing bilateral symptoms. We speculate that thigh pain is a warning sign of impending fracture and fracture-progression can be prevented with appropriate screening.
