Aim

Rifampicin as a biofilm-active antibiotic drug has a significant role in the treatment of periprosthetic joint infection (PJI). However, rifampicin resistance is an increasing threat to PJI treatment. This study aimed to evaluate the prevalence of rifampicin resistant staphylococci over time and its association with infection-free survival after PJI in a single centre in Sweden.

Metacarpal fractures represent up to 33% of all hand fractures; of which the majority can be treated non-operatively. Previous research has shown excellent putcomes with non-operative treatment yet surgical stabilisation is recommended to avoid malrotation and symptomatic shortening. It is unknown whether operative is superior to non-operative treatment in oblique or spiral metacarpal shaft fractures.

The aim of the study was to compare non-operative treatment of mobilisation with open surgical stabilisation.

42 adults (≥ 18 years) with a single displaced oblique or spiral metacarpal shaft fractures were randomly assigned in a 1:1 pattern to either non-operative treatment with free mobilisation or operative treatment with open reduction and fixation with lag screws in a prospective study. The primary outcome measure was grip-strength in the injured hand in comparison to the uninjured hand at 1-year follow-up. The Disabilities of the Arm, Shoulder and Hand Score, ranges of motion, metacarpal shortening, complications, time off work, patient satisfaction and costs were secondary outcomes.

All 42 patients attended final follow-up after 1 year. The mean grip strength in the non-operative group was 104% (range 73–250%) of the contralateral hand and 96% (range 58–121%) in the operatively treated patients. Mean metacarpal shortening was 5.0 (range 0–9) mm in the non-operative group and 0.6 (range 0–7) mm in the operative group. There were five minor complications and three revision operations, all in the operative group.

The costs for non-operative treatment were estimated at 1,347 USD compared to 3,834USD for operative treatment; sick leave was significantly longer in the operative group (35 days, range 0–147) than in the non-operative group (12 days, range 0–62) (p=0.008).

When treated with immediate free mobilization single, patients with displaced spiral or oblique metacarpal shaft fractures have outcomes that are comparable to those after operative treatment, despite some metacarpal shortening. Complication rates, costs and sick leave are higher with operative treatment. Early mobilisation of spiral or long oblique single metacarpal fractures is the preferred treatment.

Trial registration number: ClinicalTrials.gov NCT03067454

Dislocation after total hip arthroplasty in individuals treated for acute hip fracture is up to 10 times more frequent than in elective patients. Whilst approach plays a role, the effect of head sizes in conventional THA and dual mobility cups (DMC) is less studied in fracture cases.

The total dislocation rate at 1-year and 3-year revision rates were recorded in this observational study on 8,031 patients with acute hip fracture, treated with a THA 2005–2014. Swedish Arthroplasty Register data were linked with the National Patient Register. Cox multivariable regression models were fitted to calculate adjusted hazard ratios stratified by approach and head size.

The cumulative risk of dislocation during year 1 was 2.7% (95% CI 2.2–3.2) with lateral approach and 8.3% (7.3–9.3) with posterior approach (KM estimates).

In the posterior approach group DMC was associated with a lower risk of dislocation compared to cTHA=32mm (HR=0.21; 0.07–0.68), whilst a head size <32mm carried a higher risk (HR=1.47; 1.10–1.98). These differences were no longer visible when revision in general was used as outcome.

Neither of the implant designs influenced the dislocation risk when direct lateral approach was used. Male gender and severe comorbidity increased the risk. DMC with lateral approach was associated with a reduced risk of revision in general (HR=0.36; 0.13–0.99). Head size did not influence the revision risk.

When aiming to reduce the risk of any dislocation, lateral approach – regardless of cup/head design – is referable. If, for any reason, posterior approach is used, DMC is associated with the lowest risk of dislocation. This is not reflected in analysing revision in general as outcome. An interpretation could be that there are different thresholds for dislocation prompting revision.

Bone tissue engineering attempts at substituting critical size bone defects with scaffolds that can be primed with osteogenic cells, usually mesenchymal stem cells (MSC) from the bone marrow. Although overlooked, peripheral blood is a valuable source of MSC and circulating osteoprogenitors (COP), bearing a significant regenerative potential, and peripheral blood is easier to access than bone marrow. We thus studied osteodifferentiation of peripheral blood mononuclear cells (pbMNC) under different culture conditions, and how they compared to primary human osteoblasts.

pbMNC were isolated from healthy adult volunteers by Ficoll density gradient centrifugation, and they were then cultured using media supplemented with 100nM Dexamethasone, 10mM sodium β-glycero phosphate and ascorbic acid (either 40mM or 0.05mM). For comparison, primary osteoblasts were isolated from the femoral heads of patients undergoing hip arthroplasty. After 4 weeks of culture, osteogenic activation was quantified with spectrometric measurement of alkalic phosphatase (ALP) and lactate dehydrogenase (LDH) levels. The extent of osteoid mineralization was measured with Alizarin red staining. We studied the effects of 1) varying cell concentration at seeding, 2) surface coating of culture wells with collagen and 3) high compared to low ascorbic acid (40mM and 0.05mM) media.

Higher numbers of pbMNC (0.5–5.9 versus 0.062–0.25 million cells per well) at seeding resulted in a lower ALP/LDH-ratio (mean ± standard deviation), 0.39 ± 0.33 arbitrary units (AU) versus 1.36 ± 1.06 AU, but led to higher amount of osteoid production, 0.10 ± 0.06 versus 0.065 ± 0.02 AU, p < 0.05. Culture of pbMNC on collagen did not confer any difference in ALP/LDH-ratios, with 0.43 ± 0.3 AU for collagen-coated and 0.43 ± 0.41 AU for uncoated wells (p = 0.95), and we also observed no relevant difference in osteoid production (0.07 ± 0.01 AU for collagen-coated versus 0.1 ± 0.08 AU for uncoated wells, p = 0.28). Cultures of pbMNC on collagen in media supplemented with a higher concentration of ascorbic acid showed a 130% higher ALP/LDH-ratio when compared to cultures exposed to a lower ascorbic acid concentration (p < 0.05). Cultures with a low initial concentration of pbMNC (0.5 − 1 million cells) had no significantly different ALP/LDH-ratio when compared to primary human osteoblasts, but the cultures of pbMNC resulted in a 90% increase in osteoid mineralization when compared to primary human osteoblasts (p < 0.05).

These findings indicate that progenitor cells derived from peripheral blood have a significant osteogenic potential, rendering them interesting candidates for seeding of scaffolds intended to fill critical sized bone defects. pbMNC produced almost double the amount of osteoid as primary osteoblasts. The isolation of pbMSC and COP is non-invasive and easy, and they might be seeded directly onto scaffolds without prior ex-vivo expansion, a question that we intend to pursue further.

Summary Statement

Spinal cord injury is characterised by an inflammatory cascade that leads to neuronal death by neurotoxicity. In a model of spinal cord damage we successfully preserved the number of ventral horn neurons by treatment with interleukin-1 receptor antagonist (IL1RA) and neurotrophin (NT)-3.

Introduction

Several short femoral stems have been introduced in primary total hip arthroplasty, supposedly in order to save proximal bone stock. We intended to analyse primary stability, changes in periprosthetic bone mineral density (BMD), and clinical outcome after insertion of the uncemented collum femoris preserving (CFP)-femoral device.

Introduction

Stiffness of the knee after total knee arthroplasty (TKA) impairs knee function and reduces patient satisfaction. Limited preoperative range of motion (ROM) and a diagnosis of osteoarthritis seem to be associated with postoperative stiffness, and medical comorbidities such as diabetes mellitus have been discussed as predisposing factors. The present study was undertaken in order to analyse both patient-related and surgical factors that could be associated with the need for mobilization under anaesthesia (MUA) after TKA.

The aim of this experimental study was to provide an in vitro model suitable for the investigation of the complex interactions of neurons with non-neuronal cells that take place throughout the degenerative and regenerative processes induced by spinal cord injury.

Organotypic spinal cord slice cultures (OSCSC) were prepared from postnatal Wistar rats (p0–12), were sustained in vitro up to 12 days and characterized by immunohistochemistry by well-established markers such as NeuN, Calbindin, GFAP, IB4 and Nestin.

Calbindin+ neurons, distributed across the entire gray matter, were visible also after longer culture periods. NeuN+ neurons were best preserved in the dorsal horn, whereas large NeuN+ and ChAT+ motoneurons in the ventral horn vanished after 3 days in vitro. GFAP+ astro-cytes, initially restricted to the white matter, invaded the gray matter of OSCSC early during the culture period. Microglial cells, stained by Griffonia simplicifolia isolectin B4, were rapidly activated in the dorsal tract and in the gray matter, but declined in number with time. Nestin-immunoreactivity was found in animals of all age groups, either in cells interspersed in the ependymal lining around the central canal, or in cells resembling protoplasmic astrocytes. OSCSC derived from p0 or p3 animals showed a better preservation of the cytoarchitecture than cultures derived from older animals.

In summary, OSCSC contain defined neuronal populations, the cytoarchitecture is partially preserved, and the glial reaction is self-limited. Our model of OSCSC could prove useful in future experiments on the patho-physiology of spinal cord injury

Aim of this experimental study was to develop an in vitro model that simplifies the study of various factors regulating neuronal regeneration.

An in vitro-system that allows co-culture of slices from rat motorcortex and spinal cord (p4) was established. Two groups of cultures were investigated: In the first group, intact spinal cord slices were cultured adjacent to motorcortex slices, while in the second group the spinal cord slices were sagitally cut into halves, with the sectioned interface placed directly adjacent to the motorcortex, in order to prevent the spinal white matter from interference. Each group was further divided into two subgroups: The NT-3 group, where the culture medium contained 50 ng/ml NT-3 and the control group treated with normal culture medium. Motorcortex pyramidal neurons were anterogradely labelled with MiniRuby, a 10 kD biotinylated dextran amine.

After 4 days the co-cultures were propagated, and axonal sprouting occurred. The group of co-cultures treated with NT-3 showed an improved cortical cytoarchitecture, and sprouting axons were more frequently observed. In NT-3-treated co-cultures where spinal cord gray matter was directly opposed to cortical slices sprouting axons entered the adjacent spinal cord tissue. This phenomenon was not observed if spinal white matter was opposed to the cortical slices, or if NT-3 was absent.

Our data suggest that the absence of repellent factors such as white matter and the presence of neuro-trophic factors promote axonal sprouting. Co-cultures of motorcortex and spinal cord slices combined with anterograde axonal labelling could provide a valuable in vitro model for the simplified screening of factors influencing corticospinal tract regeneration

Background: Hydroxyapatite (HA) coating is widely used for total hip arthroplasty as it has been suggested to improve implant ingrowth and long-term stability. However, the evidence behind the use of HA in femoral stems is ambiguous.

Methods: We investigated a non-cemented, tapered titanium femoral stem that was available either with or without HA coating. This stem had been used in 3,116 total hip arthroplasties (THAs) in 2,608 patients registered in the Swedish Hip Arthroplasty Register (1992–2007). Kaplan-Meier survival analysis and a Cox regression model including type of coating, age, sex, primary diagnosis, and the type of cup fixation were used to calculate adjusted risk ratios (RR) of the risk for revision for various reasons.

Results: 63.7% of the stems were coated with HA, 36.3% were uncoated. It was found that the investigated HA-coated stem had an excellent 10-year survivorship of 97.7% (95% CI 96.5–98.9), and that the stem without HA coating had a 10-year survivorship of 97.6% (95% CI 96.2–99.0) when revision due to any reason was defined as the endpoint. There was no significant difference between these two groups (p> 0.05, log rank Mantel-Cox). A Cox regression model showed that the presence of HA coating did not significantly influence the risk of stem revision due to any reason (RR 1.3; 95% CI 0.7–2.4), or due to aseptic loosening (RR 1.0; 95% CI 0.3–3.4). The risk for revision due to infection, dislocation, or fracture was also not affected by the presence of HA coating.

Interpretation: Our results show HA coating of this non-cemented tapered stem with excellent 10-year survivorship does not affect the risk for revision. The assumed beneficial effect of HA coating of femoral stems in total hip arthroplasty is thus questionable.

Background: Hydroxyapatite (HA) is the main inorganic component of bone, and HA coating is widely used on acetabular cups in hip arthroplasty. It has been suggested that this surface finish improves cup survival, but there is little evidence to support this.

Patients and methods: All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 with an uncemented acetabular implant that was available with or without HA coating were identified. A study population of 8,043 hips with the most common cup types manufactured either with or without HA coating (Harris-Galante, Romanus and Trilogy) was investigated. Kaplan-Meier survival analysis and a Cox regression model including type of coating, age, sex, primary diagnosis, cup type, and type of stem fixation were used to calculate adjusted risk ratios (RR) of the risk for revision.

Results: Kaplan-Meier analysis of all patients indicated a non-significant trend towards inferior performance of the HA-coated cups (p=0.78). When stratified for age, Kaplan-Meier analysis revealed inferior survival of HA-coated cups when compared to non-coated cups in the age group < 50 years (p=0.031). A Cox regression model showed that HA coating was a significant risk factor for cup revision due to aseptic loosening (adjusted RR 1.645; 95% CI 1.315–2.058). Age at primary arthroplasty < 50 years, a diagnosis of paediatric hip disease, a cemented stem, and the Romanus and Harris-Galante cup types were also associated with significantly increased risk for cup revision due to aseptic loosening. There was no difference in the hazard patterns when the risk for revision for any reason was chosen as the endpoint of the analysis. The risk for revision due to infection was not influenced by the type of coating.

Discussion: Our results derived from register data on 8,043 hips indicate that HA coating does not enhance survival of cups when using aseptic loosening as an endpoint. On the contrary, hydroxyapatite coating is a significant risk factor for cup revision due to aseptic loosening when adjusted for other covariates such as age, sex, cup design and primary diagnosis. HA coating cannot be generally recommended as a surface treatment of acetabular cups in younger patients. This conclusion is medically and economically relevant, as many young patients today receive HA-coated cups, and because HA-coated implants are more expensive.

INTRODUCTION: Metal-on-metal alloarthroplasty of the hip is gaining popularity in order to avoid complications associated with polyethylene wear. On the other hand, metal-on-metal articulations release metal ions, the biological effects of which remain unclear. Genetic and immunological changes have been associated with increased metal ion levels in arthroplasty patients. We intended to study the outcome after metal-on-metal arthroplasty of the hip with a focus on the toxicologically and immunologically relevant metal ions chromium, cobalt, nickel, and manganese.

PATIENTS AND METHODS: A prospective, randomised study was designed where all patients received a cemented arthroplasty of the hip, either with a metal-on-metal bearing (Metasul ®; 28 patients) or with a metal-on-polyethylene bearing (Protasul ®, 26 patients). Only patients with primary osteoarthritis of the hip and without other metallic implants were included (mean age 65 years, range 45–74). Follow-up was performed after a minimum of two years. Clinical outcome was measured by the Harris hip score and the SF36, and radiographic analysis was undertaken by plain radiography. Metal ion concentrations in patient serum were analysed by high-resolution plasma mass spectrometry.

RESULTS: It was found that the clinical outcome was almost identical in both groups with respect to Harris hip score and SF36, and radiographic signs of osteolyses or loosening did not occur in any group. In the metal-on-metal group, chromium concentrations increased 4.1 fold and cobalt concentrations increased 7.6 fold when compared to preoperative values (p< 0.05; Wilcoxon Mann Whitney Test), whereas nickel and manganese concentrations did not change significantly. In the metal-on-polyethylene group, no significant increase in the concentration of any ion occurred.

DISCUSSION: In conclusion, metal-on-metal and metal-on-polyethylene arthroplasties of the hip provide equal clinical and radiographic outcomes in the medium term, but the concentrations of chromium and cobalt increase considerably after metal-on-metal arthroplasty. Importantly, the allergogenic and previously not assessed ions nickel and manganese show no significant changes in the medium term after any type of hip alloarthroplasty. To our knowledge, this is the first study that addresses manganese and nickel concentrations in a prospective, randomized setting, and our patients will be followed further with respect to possible immunological and genetic changes.

Aims: Spinal fractures cause compression of the spinal cord, and nerve cells and nerve fibers are severely damaged. The immediate mechanical injury is subsequently enhanced in a process called secondary damage, and it has been proposed that inflammatory cells such as microglial cells and cytokines such as interleukin (IL)-1 damage nerves and nerve fibers that were initially not affected by spinal cord compression. It was the aim of this study a) to investigate the role of microglial cells and IL-1 in neuronal damage, and b) to investigate whether the anti-inflammatory agent IL-1 receptor antagonist (IL-1ra) that has been successfully used in patients with polyarthritis can protect neurons by inhibiting microglial activation or by antagonising cellular effects of IL-1.

Methods: We investigated the effects of IL-1 and IL-1ra on neurons and microglial cells in organotypic hippocampal slice cultures (OHSC): OHSC derived from rats were excitotoxically lesioned after 6 days in vitro by application of N-methyl-d-aspartate (NMDA) and treated with (IL)-1 (6 ng/ml) or IL-1ra (40, 100, or 500 ng/ml) for up to 10 days. OHSC were then quantitatively analyzed by confocal laser scanning microscopy after fluorescent labeling of neurons and microglial cells.

Results: Treatment of unlesioned OHSC with IL-1 did not induce neuronal damage although the number of microglial cells increased. NMDA-lesioning alone resulted in a massive increase in the number of microglial cells and degenerating neurons. Treatment of NMDA-lesioned OHSC with IL-1 exacerbated neuronal cell death and further enhanced microglial cell numbers. Treatment of NMDA-lesioned cultures with IL-1ra significantly attenuated NMDA-induced neuronal damage and reduced the number of microglial cells, whereas application of IL-1ra in unlesioned OHSC did not induce significant changes in either cell population.

Conclusion: Our findings indicate that a) IL-1 directly affects neurons and acts independently from infiltrating hematogenous cells, b) IL-1 induces microglial activation although it is not neurotoxic per se, c) IL-1 enhances excitotoxic neuronal damage and microglial activation, d) IL-1ra, even when only applied for short periods of time, reduces neuronal cell death and induces a dose-dependent decrease in the number of microglial cells after excitotoxic damage. These findings suggest that IL-1ra has the potential to exert beneficial effects in patients with spinal fractures, and this encourages further in vivo-studies.

This study presents an historical review of the treatment of talipes equino-varus during the last centuries. The aim of the study was to show how knowledge about the pathogenesis and the progress of new techniques in orthopaedic surgery (plaster of Paris, anaesthesiology, asepsis, antisepsis) have influenced the treatment of this disease during the centuries.

This investigation is based on a study of the library of the German Orthopaedic and Science Museum that has more than 3000 historical books and theses from the middle of the 19th century to the present time.

In the 18th and 19th century there were different theories about the pathogenesis of clubfoot. For example, Paré was of the opinion that secondary forces were responsible for the deformity. Camper and Wolff were convinced that intrauterine pressure on the extremities was the reason for pes equinovarus. Little, Stromeyer and Delpech believed that shortening of the muscles was the origin. The pathogenesis of the clubfoot is still obscure.

The concept of therapy with redression and retention during the first month has not changed since Hippocrates. However, the techniques of redression and retention have changed during the decades. Machines and rural instruments were used for redression until the end of the 19th century (Lorenz, Thomas). Retention was improved by the development of new splints (Arceo, Venel, Scarpa). The introduction of plaster of Paris (Mathysen) in the treatment of the clubfoot led to a further improvement of retention in early treatment.

A new era began with asepsis and anaesthesia. These techniques allowed progress in the operative therapy of the tendons. The open and subcutaneous tenotomy was developed by Delpech, Dieffenbach, and Stromeyer.

In spite of the operative possibilities, we conclude that conservative treatment still has a major role in the concept of treatment for equinovarus.