In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits. The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.Objective
Methods
Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) Objectives
Materials and Methods
Giant cell tumours (GCT) of the synovium and
tendon sheath can be classified into two forms: localised (giant
cell tumour of the tendon sheath, or nodular tenosynovitis) and
diffuse (diffuse-type giant cell tumour or pigmented villonodular
synovitis). The former principally affects the small joints. It
presents as a solitary slow-growing tumour with a characteristic
appearance on MRI and is treated by surgical excision. There is
a significant risk of multiple recurrences with aggressive diffuse
disease. A multidisciplinary approach with dedicated MRI, histological assessment
and planned surgery with either adjuvant radiotherapy or systemic
targeted therapy is required to improve outcomes in recurrent and
refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has
been advocated as an alternative to arthrotomy, there is a significant
risk of inadequate excision and recurrence, particularly in the
posterior compartment of the knee. For local disease partial arthroscopic
synovectomy may be sufficient, at the risk of recurrence. For both
local and diffuse intra-articular disease open surgery is advised
for recurrent disease. Marginal excision with focal disease will
suffice, not dissimilar to the treatment of GCT of tendon sheath.
For recurrent and extra-articular soft-tissue disease adjuvant therapy,
including intra-articular radioactive colloid or moderate-dose external
beam radiotherapy, should be considered.
We retrospectively reviewed 30 patients with
a diffuse-type giant-cell tumour (Dt-GCT) (previously known as pigmented
villonodular synovitis) around the knee in order to assess the influence
of the type of surgery on the functional outcome and quality of
life (QOL). Between 1980 and 2001, 15 of these tumours had been
treated primarily at our tertiary referral centre and 15 had been
referred from elsewhere with recurrent lesions. The mean follow-up was 64 months (24 to 393). Functional outcome
and QOL were assessed with range of movement and the Knee injury
and Osteoarthritis Outcome Score (KOOS), the Musculoskeletal Tumour
Society (MSTS) score, the Toronto Extremity Salvage Score (TESS)
and the SF-36 questionnaire. There was recurrence in four of 14
patients treated initially by open synovectomy. Local control was
achieved after a second operation in 13 of 14 (93%). Recurrence
occurred in 15 of 16 patients treated initially by arthroscopic
synovectomy. These patients underwent a mean of 1.8 arthroscopies
(one to eight) before open synovectomy. This achieved local control
in 8 of 15 (53%) after the first synovectomy and in 12 of 15 (80%)
after two. The functional outcome and QOL of patients who had undergone
primary arthroscopic synovectomy and its attendant subsequent surgical
procedures were compared with those who had had a primary open synovectomy
using the following measures: range of movement (114º Those who had undergone open synovectomy needed fewer subsequent
operations. Most patients who had been referred with a recurrence
had undergone an initial arthroscopic synovectomy followed by multiple
further synovectomies. At the final follow-up of eight years (2
to 32), these patients had impaired function and QOL compared with
those who had undergone open synovectomy initially. We conclude that the natural history of Dt-GCT in patients who
are treated by arthroscopic synovectomy has an unfavourable outcome,
and that primary open synovectomy should be undertaken to prevent
recurrence or residual disease. Cite this article:
The treatment of chronic osteomyelitis often
includes surgical debridement and filling the resultant void with antibiotic-loaded
polymethylmethacrylate cement, bone grafts or bone substitutes.
Recently, the use of bioactive glass to treat bone defects in infections
has been reported in a limited series of patients. However, no direct comparison
between this biomaterial and antibiotic-loaded bone substitute has
been performed. In this retrospective study, we compared the safety and efficacy
of surgical debridement and local application of the bioactive glass
S53P4 in a series of 27 patients affected by chronic osteomyelitis
of the long bones (Group A) with two other series, treated respectively
with an antibiotic-loaded hydroxyapatite and calcium sulphate compound
(Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded
demineralised bone matrix (Group C; n = 22). Systemic antibiotics
were also used in all groups. After comparable periods of follow-up, the control of infection
was similar in the three groups. In particular, 25 out of 27 (92.6%)
patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out
of 22 (86.3%) in Group C showed no infection recurrence at means
of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up,
respectively, while Group A showed a reduced wound complication
rate. Our results show that patients treated with a bioactive glass
without local antibiotics achieved similar eradication of infection
and less drainage than those treated with two different antibiotic-loaded
calcium-based bone substitutes. Cite this article:
Systemic antibiotics reduce infection in open
fractures. Local delivery of antibiotics can provide higher doses
to wounds without toxic systemic effects. This study investigated
the effect on infection of combining systemic with local antibiotics
via polymethylmethacrylate (PMMA) beads or gel delivery. An established Combined local and systemic antibiotics were superior to systemic
antibiotics alone at reducing the quantity of bacteria recoverable
from each group (p = 0.002 for gel; p = 0.032 for beads). There
was no difference in the bacterial counts between bead and gel delivery
(p = 0.62). These results suggest that local antibiotics augment the antimicrobial
effect of systemic antibiotics. Although no significant difference
was found between vehicles, gel delivery offers technical advantages
with its biodegradable nature, ability to conform to wound shape
and to deliver increased doses. Further study is required to see
if the gel delivery system has a clinical role. Cite this article:
Heterotopic ossification (HO) is perhaps the
single most significant obstacle to independence, functional mobility, and
return to duty for combat-injured veterans of Operation Enduring
Freedom and Operation Iraqi Freedom. Recent research into the cause(s)
of HO has been driven by a markedly higher prevalence seen in these
wounded warriors than encountered in previous wars or following
civilian trauma. To that end, research in both civilian and military
laboratories continues to shed light onto the complex mechanisms
behind HO formation, including systemic and wound specific factors,
cell lineage, and neurogenic inflammation. Of particular interest,
non-invasive
Bone cements produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement, which may not be apparent to surgeons, can also affect these properties. The supplier of Palacos bone cement with added gentamicin changed in 2005. We carried out a study to examine the mechanical characteristics and antibiotic elution of Schering-Plough Palacos, Heraeus Palacos and Depuy CMW Smartset bone cements. Both Heraeus Palacos and Smartset bone cements performed significantly better than Schering-Plough Palacos in terms of mechanical characteristics, with and without additional vancomycin (p <
0.001). All cements show a deterioration in flexural strength with increasing addition of vancomycin, albeit staying above ISO minimum levels. Both Heraeus Palacos and Smartset elute significantly more gentamicin cumulatively than Schering-Plough Palacos. Smartset elutes significantly more vancomycin cumulatively than Heraeus Palacos. The improved antibiotic elution characteristics of Smartset and Heraeus Palacos are not associated with a deterioration in mechanical properties. Although marketed as the ‘original’ Palacos, Heraeus Palacos has significantly altered mechanical and antibiotic elution characteristics compared with the most commonly-used previous version.
A clinical investigation into a new bone void filler is giving
first data on systemic and local exposure to the anti-infective
substance after implantation. A total of 20 patients with post-traumatic/post-operative bone
infections were enrolled in this open-label, prospective study.
After radical surgical debridement, the bone cavity was filled with
this material. The 21-day hospitalisation phase included determination
of gentamicin concentrations in plasma, urine and wound exudate, assessment
of wound healing, infection parameters, implant resorption, laboratory
parameters, and adverse event monitoring. The follow-up period was
six months. Objective
Method
Based on the first implementation of mixing antibiotics
into bone cement in the 1970s, the Endo-Klinik has used one stage
exchange for prosthetic joint infection (PJI) in over 85% of cases.
Looking carefully at current literature and guidelines for PJI treatment,
there is no clear evidence that a two stage procedure has a higher
success rate than a one-stage approach. A cemented one-stage exchange
potentially offers certain advantages, mainly based on the need
for only one operative procedure, reduced antibiotics and hospitalisation time.
In order to fulfill a one-stage approach, there are obligatory pre-,
peri- and post-operative details that need to be meticulously respected,
and are described in detail. Essential pre-operative diagnostic
testing is based on the joint aspiration with an exact identification
of any bacteria. The presence of a positive bacterial culture and
respective antibiogram are essential, to specify the antibiotics
to be loaded to the bone cement, which allows a high local antibiotic
elution directly at the surgical side. A specific antibiotic treatment
plan is generated by a microbiologist. The surgical success relies
on the complete removal of all pre-existing hardware, including
cement and restrictors and an aggressive and complete debridement
of any infected soft tissues and bone material. Post-operative systemic
antibiotic administration is usually completed after only ten to
14 days. Cite this article:
We reviewed systematically the published evidence on the effectiveness of antibiotic prophylaxis for the reduction of wound infection in patients undergoing total hip and total knee replacement. Publications were identified using the Cochrane Library, MEDLINE, EMBASE and CINAHL databases. We also contacted authors to identify unpublished trials. We included randomised controlled trials which compared any prophylaxis with none, the administration of systemic antibiotics with that of those in cement, cephalosporins with glycopeptides, cephalosporins with penicillin-derivatives, and second-generation with first-generation cephalosporins. A total of 26 studies (11 343 participants) met the inclusion criteria. Methodological quality was variable. In a meta-analysis of seven studies (3065 participants) antibiotic prophylaxis reduced the absolute risk of wound infection by 8% and the relative risk by 81% compared with no prophylaxis (p <
0.00001). No other comparison showed a significant difference in clinical effect. Antibiotic prophylaxis should be routine in joint replacement but the choice of agent should be made on the basis of cost and local availability.
Despite local treatment with systemic chemotherapy in Ewing’s sarcoma family tumours (ESFT), patients with detectable metastases at presentation have a markedly worse prognosis than those with apparently localised disease. We investigated the clinical, pathological and laboratory differences in 888 patients with ESFT, 702 with localised disease and 186 with overt metastases at presentation, seen at our institution between 1983 and 2006. Multivariate analyses showed that location in the pelvis, a high level of serum lactic dehydrogenase, the presence of fever and a short interval between the onset of symptoms and diagnosis were indicative of metastatic disease. The rate of overt metastases at presentation was 10% without these four risk factors, 22.7% with one, 31.4% with two, and 50% for those with three or four factors. We concluded that in ESFT the site, the serum level of lactic dehydrogenase, fever, and the interval between the onset of symptoms and diagnosis are indicators of tumours having a particularly aggressive metastatic behaviour.
Mesenchymal stem-cell based therapies have been
proposed as novel treatments for intervertebral disc degeneration,
a prevalent and disabling condition associated with back pain. The
development of these treatment strategies, however, has been hindered
by the incomplete understanding of the human nucleus pulposus phenotype
and by an inaccurate interpretation and translation of animal to
human research. This review summarises recent work characterising
the nucleus pulposus phenotype in different animal models and in
humans and integrates their findings with the anatomical and physiological
differences between these species. Understanding this phenotype
is paramount to guarantee that implanted cells restore the native
functions of the intervertebral disc. Cite this article:
The April 2012 Wrist &
Hand Roundup360 looks at releasing the trigger finger, function in the osteoarthritic hand, complex regional pain syndrome, arthroscopic ligamentoplasty for the injured scapholunate ligament, self-concept and upper limb deformities in children, wrist arthroscopy in children, internal or external fixation for the fractured distal radius, nerve grafting, splinting the PIPJ contracture, and finding the stalk of a dorsal wrist ganglion
We used a goat model of a contaminated musculoskeletal defect to determine the effectiveness of rapidly-resorbing calcium-sulphate pellets containing amikacin to reduce the local bacterial count. Our findings showed that this treatment eradicated the bacteria quickly, performed as well as standard polymethylmethacrylate mixed with an antibiotic and had many advantages over the latter. The pellets were prepared before surgery and absorbed completely. They released all of the antibiotic and did not require a subsequent operation for their removal. Our study indicated that locally administered antibiotics reduced bacteria within the wound rapidly. This method of treatment may have an important role in decreasing the rate of infection in contaminated wounds.
Infection of a total hip replacement (THR) requires component removal and thorough local debridement. Usually, long-term antibiotic treatment in conjunction with a two-stage revision is required. This may take several months. One-stage revision using antibiotic-loaded cement has not gained widespread use, although the clinical and economic advantages are obvious. Allograft bone may be impregnated with high levels of antibiotics, and in revision of infected THR, act as a carrier providing a sustained high local concentration. We performed 37 one-stage revision of infected THRs, without the use of cement. There were three hips which required further revision because of recurrent infection, the remaining 34 hips (92%) stayed free from infection and stable at a mean follow-up of 4.4 years (2 to 8). No adverse effects were identified. Incorporation of bone graft was comparable with unimpregnated grafts. Antibiotic-impregnated allograft bone may enable reconstruction of bone stock, insertion of an uncemented implant and control of infection in a single operation in revision THR for infection.
Migration of the acetabular component may give rise to oval-shaped bone defects in the acetabulum. The oblong implant is designed to fill these defects and achieve a stable cementless anchorage with no significant bone loss. We prospectively reviewed 133 oblong long oblique revision components at a mean follow-up of 9.74 years (0.6 to 14). All had been used in revisions for defects of type IIB to IIIB according to Paprosky. Aseptic loosening was the reason for revision in 11 cases (8.3%) and deep infection in seven (5.3%). The probability of implant survival over a 12-year follow-up estimated by the Kaplan-Meier method gave a survival rate of 0.85% respectively 0.90% when deep infection was excluded as the endpoint. Our study supports the use of these components in defects from IIB to IIIA. The main precondition for success is direct contact of more than half of the surface of the implant with the host acetabular bone.
Our aim was to determine the effect of delay to surgery on the time to discharge, in-hospital death, the presence of major and minor medical complications and the incidence of pressure sores in patients with a fracture of the hip. All patients admitted to Vancouver General Hospital with this injury between 1998 and 2001 inclusive were identified from our trauma registry. A review of the case notes was performed to determine the delay in time from admission to surgery, age, gender, type of fracture and medical comorbidities. A time-to-event analysis was performed for length of stay. Additionally, a Cox proportional hazards model was used to determine the effect of delay to surgery on the length of stay while controlling for other pertinent confounding factors. Using logistical regression we determined the effect of delay to surgery on in-hospital death, medical complications and the presence of pressure sores, while controlling for confounding factors. Delay to surgery (p = 0.0255), comorbidity (p <
0.0001), age (p <
0.0001) and type of fracture (p = 0.0004) were all significant in the Cox proportional hazards model for increased time to discharge. Delay to surgery was not a significant predictor of in-hospital mortality. However, a delay of more than 24 hours was a significant predictor of a minor medical complication (odds ratio (OR) 1.53, 95% confidence interval (CI) 1.05 to 2.22), while a delay of more than 48 hours was associated with an increased risk of a major medical complication (OR 2.21, 95% CI 1.01 to 4.34), a minor medical complication (OR 2.27, 95% CI 1.38 to 3.72) and of pressure sores (OR 2.29, 95% CI 1.19 to 4.40). Patients with a fracture of the hip should have surgery early to lessen the time to acute-care hospital discharge and to minimise the risk of complications.
We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.
Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known. The aims of this randomised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients (56 hips) over a five-year period, following total hip replacement. At five years, 37 patients (42 hips) returned for assessment. The Harris hip scores were similar in the pamidronate and placebo groups throughout the study. Also at five years, four patients, two from each group had osteolytic lesions on plain radiography. These were located around the acetabular component in three patients and in the femoral calcar in one. The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years. Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement.