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Background Multiply revised total knee arthroplasties (TKAs) may present with large anterior soft tissue defects, which can be challenging to reconstruct. In the rare cases where local flaps are insufficient, we use free latissimus dorsi (LD) myocutaneous flaps to achieve soft tissue coverage. This study looked to determine implant survivorship, infection status, and patient-reported outcomes of patients undergoing simultaneous revision TKA and LD flaps in a tertiary unit. Methods This was a retrospective study of 18 consecutive patients who had revision TKA and free LD flap reconstruction. Twelve were male and the median age was 65 years (range, 35-83). Patients had undergone a median of 4 previous arthroplasty procedures (range, 3-6). Median follow-up was 49 months (range, 18 to 110). The primary outcome was revision-free implant survival. Secondary outcomes included soft tissue integrity, Oxford Knee Score, and EuroQol 5-domain score at latest follow-up. Results At latest follow-up, 14 of 18 patients had maintained their implant. Seven patients were infection-free, 7 were on suppressive antibiotics with the implant in situ, and 4 had undergone above-knee amputation. Five-year implant survival was 75% (95% confidence interval, 46-90). At median follow-up (49 months), mean Oxford Knee Score was 13.4 (range, 2-35) and mean EuroQol 5-domain index was 0.071 (range:−0.427 to 0.747). Conclusion LD free flap is a viable option for limb salvage in patients with large anterior soft tissue defects following multiple revisions of TKA. However, functional outcomes can be poor and there is a significant risk of ongoing infection and amputation in this complex patient cohort.

Background Autologous chondrocyte implantation (ACI) is a NICE-approved technique to regenerate hyaline cartilage in chondral and osteochondral defects (OCDs). The drawbacks of ACI include that it requires a two-stage approach, involves a lengthy rehabilitation process and is expensive. Bone marrow harvest with mesenchymal stem cell transplantation using a single-stage procedure and an accelerated rehabilitation programme has been developed to overcome this. The aim of this paper is to describe the surgical technique for stem cell transplantation of the knee for OCDs with reference to case examples. Methods The surgical technique for stem cell transplantation of the knee for OCDs is described, with reference to three cases. Magnetic resonance imaging was performed at six months postoperatively. Results The surgical technique is described in this paper. The three patient cases described all improved clinically with reduced pain and improved function at a minimum of six months follow-up. Conclusions Stem cell transplantation has the potential to produce favourable outcomes for patients with osteochondral defects of the knee. This single-stage approach and accelerated rehabilitation is associated with reduced financial costs. A long-term prospective study of this technique is currently underway at our institution and randomised controlled trials are planned to demonstrate the effectiveness over other techniques.

Small interfering RNAs (siRNAs) conjugated to N-acetylgalactosamine (GalNAc) ligands have been used to treat disease in patients. However, conjugates with other ligands deliver siRNA less efficiently, limiting the development of new targeted therapies. Most approaches to enhancing the potency of such conjugates have concentrated on increasing ligand effectiveness and/or the chemical stability of the siRNA drug. One complementary and unexplored alternative is to increase the number of siRNAs delivered per ligand. An ideal system would be a single chemical entity capable of delivering multiple copies of an oligonucleotide drug and/or several such drugs simultaneously. Here we report that siRNAs can be stably linked together under neutral aqueous conditions to form chemically defined siRNA “multimers,” and that these multimers can be delivered in vivo by a GalNAc ligand. Conjugates containing multiple copies of the same siRNA showed enhanced activity per unit of ligand, whereas siRNAs targeting different genes linked to a single ligand facilitated multigene silencing in vivo; this is the first demonstration of silencing several genes simultaneously in vivo using ligand-directed multimeric siRNA. Multimeric oligonucleotides represent a powerful and practical new approach to improve intracellular conjugate delivery.

This case series reports familial cases of nodular oncocytic hyperplasia (NOH) diagnosed in a mother and her son, 15 years apart. A 39-year-old man presented in 2003 with a lump below his left ear. Magnetic resonance imaging (MRI) performed showed multifocal parotid nodules and a diagnosis of NOH was histopathologically confirmed following left total parotidectomy. Two years later, he represented with similar symptoms on the right side. NOH was diagnosed following excision of his right parotid gland. In 2018, his 73-year-old mother presented with left ear pain and a lump below her left ear. An MRI scan showed multiple lesions within both parotid glands and bilateral NOH was once again diagnosed following a left superficial parotidectomy and right total parotidectomy. We believe that this is the first reported case of bilateral familial NOH.

Background Revision knee replacement (KR) is both challenging for the surgical team and expensive for the healthcare provider. Limited high quality evidence is available to guide decision-making. Aim To provide guidelines for surgeons and units delivering revision KR services. Methods A formal consensus process was followed by BASK’s Revision Knee Working Group, which included surgeons from England, Wales, Scotland and Northern Ireland. This was supported by analysis of National Joint Registry data. Results There are a large number of surgeons operating at NHS sites who undertake a small number of revision KR procedures. To optimise patient outcomes and deliver cost-effective care high-volume revision knee surgeons working at high volume centres should undertake revision KR. This document outlines practice guidelines for units providing a revision KR service and sets out: The current landscape of revision KR in England, Wales and Northern Ireland. Service organisation within a network model. The necessary infrastructure required to provide a sustainable revision service. Outcome metrics and auditable standards. Financial mechanisms to support this service model. Conclusions Revision KR patients being treated in the NHS should be provided with the best care available. This report sets out a framework to both guide and support revision KR surgeons and centres to achieve this aim.

This article is an expansion of a lecture given in the British Orthopaedic Association (BOA) Congress in Liverpool in 2019 as part of a symposium on infected knee replacement. It is designed to provide pointers and advice to surgeons on how these patients can be referred, investigated, and managed. The management of periprosthetic infection necessitates many decisions to be made to provide the patient with the best advice and treatment. This is a discussion of the philosophies of periprosthetic knee infection. It is not a definitive guide nor a metanalysis of scientific papers. These are the subjective views of the author and generalise decision making. All decisions should remain tailored to the patient's needs.

Background A two-stage revision remains the gold standard to eradicate deep infection in total knee arthroplasty. Higher failure rates are associated with a number of factors including poly-microbial infections, multiresistant organisms and previous operations. The aims are to investigate [1] the overall success rate of a two-stage revision for infections in TKA, [2] the outcome of repeat two-stage revisions in recurrent infections and [3] the factors affecting the outcomes of such cases. Methods We present the outcomes of a consecutive, retrospective case series of 51 periprosthetic joint infections managed with a two-stage revision knee arthroplasty over a three year period. Results Forty-six (90%) of 51 were referred from other hospitals. Infection was successfully eradicated in 24 (65%) of 37 patients undergoing an initial two-stage procedure. Following a failed two-stage revision, a repeat two-stage revision was performed in 19 patients eradicating infection in 8 (42%). A third two-stage was performed in five of these patients eradicating infection in three with an average follow-up of 43months. Multidrug resistance was present in 69%, and 47% of the patients were infected with multiple organisms. All unsuccessful outcomes involved at least one multidrug-resistant organism compared to 43% in the successful cohort ( P =0.0002). Serological markers prior to a second-stage procedure were not significantly different between successful and unsuccessful outcome groups. Conclusion Single or multiple two-stage revisions can eradicate infection despite previous failed attempts. In this series, failure is associated with multidrug resistance, previous failed attempts to eradicate infection and a less favourable host response. Level of evidence IV

OBJECTIVE The purpose of this study was to compare the effectiveness of detecting proximal carious lesions utilizing a new near-infrared transillumination (NIRTI) system (CariVu, Dexis) to traditional digital bitewing radiography (BWXR). MATERIALS AND METHODS Thirty patients received four posterior BWXRs and all premolars and molars were individually imaged with the NIRTI device. Sixty-seven proximal carious lesions were classified based on their depth into enamel or dentin for both BWXR and NIRTI images. RESULTS The caries depth classification between the two systems were strongly correlated (rs = 0.66; Spearman range: 0.60-0.79 = strong) and significant (P

Total knee arthroplasty (TKA) in limbs affected by poliomyelitis is a technically challenging procedure. These patients often demonstrate acquired articular and metaphyseal angular deformities, bone loss, narrowness of the intramedullary canals, impaired quadriceps strength, flexion contractures and ligamentous laxity producing painful hyperextension. Thus, using condylar knee designs in these patients will likely result in early failure because of instability and abnormal load distribution. The aim of this study was to assess the outcomes associated with use of the customised (SMILES) rotating-hinge knee system at our institution for TKA in poliomyelitis-affected limbs. We retrospectively reviewed the outcome of 14 TKAs using the (SMILES) prosthesis in 13 patients with limbs affected by poliomyelitis. All patients had painful unstable knees with hyperextension. There were ten females and three males with a mean age of 66 years (range 51–84) at time of surgery. Patients were followed up clinically, radiologically and functionally with the Oxford knee score (OKS). Mean follow-up was 72 months (16–156). There were no immediate or early complications. One patient fell and sustained a peri-prosthetic fracture at seven months requiring revision to a longer stem. Radiological evaluation showed satisfactory alignment with no signs of loosening in all cases. Mean OKS improved from 11.6 (4–18) to 31.5 (18–40) postoperatively (p

Due to an increasing lifespan, patients with osteogenesis imperfecta have a high incidence of hip osteoarthritis. The presence of recurrent fractures and deformities make primary and particularly revision total hip arthroplasty challenging. We present a series of patients with osteogenesis imperfecta undergoing total hip arthroplasty at a tertiary referral centre with a median follow-up of 7.6 years (4 to 35 years). There were four primary total hip arthroplasties and eight revision total hip arthroplasties performed in four patients. Three femoral components were custom computer assisted design computer assisted manufactured. The survival rate of the primary total hip arthroplasty was 16% and there were ten complications: five intraoperative fractures, one case of septic loosening and four cases of aseptic loosening. Patients with pre-operative acetabular protrusio were significantly more likely to require revision surgery (p = 0.02). At latest follow-up, the median Oxford hip score was 41 (37 to 46). As the largest series of primary and revision total hip arthroplasty performed in patients with osteogenesis imperfecta, we report good medium to long-term outcomes. Pre-Operative planning and consideration of custom made prostheses have an important role in these complex cases.

For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven.To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion.A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013.Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]).Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%).Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20).Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy.isrctn.org Identifier: ISRCTN33288337.

We conducted a prospective single-blinded randomised controlled trial to compare the functional and quality of life outcomes in two groups of patients between 60 and 80 years of age undergoing THR; the first receiving a small head (28–32 mm) metal on polyethylene (MoP) articulation, and the second receiving a large head (44–54 mm) metal on metal (MoM) articulation. We recruited 49 patients and randomised them into one of the two groups (22 MoP and 27 MoM). The results demonstrated no statistical difference in any of the assessed functional outcomes at any follow-up point (p>0.05). There were no dislocations or revisions in either group. Although it has been suggested that large head MoM articulations in THA offer superior stability and function, our results suggest that small head MoP articulations can achieve comparable ROM, function and quality of life at short-term follow-up.

Patients with skeletal dysplasia are prone to developing advanced osteoarthritis of the knee requiring total knee replacement (TKR) at a younger age than the general population. TKR in this unique group of patients is a technically demanding procedure owing to the deformity, flexion contracture, generalised hypotonia and ligamentous laxity. We retrospectively reviewed the outcome of 11 TKRs performed in eight patients with skeletal dysplasia at our institution using the Stanmore Modular Individualised Lower Extremity System (SMILES) custom-made rotating-hinge TKR. There were three men and five women with mean age of 57 years (41 to 79). Patients were followed clinically and radiologically for a mean of seven years (3 to 11.5). The mean Knee Society clinical and function scores improved from 24 (14 to 36) and 20 (5 to 40) pre-operatively, respectively, to 68 (28 to 80) and 50 (22 to 74), respectively, at final follow-up. Four complications were recorded, including a patellar fracture following a fall, a tibial peri-prosthetic fracture, persistent anterior knee pain, and aseptic loosening of a femoral component requiring revision. Our results demonstrate that custom primary rotating-hinge TKR in patients with skeletal dysplasia is effective at relieving pain, with a satisfactory range of movement and improved function. It compensates for bony deformity and ligament deficiency and reduces the likelihood of corrective osteotomy. Patellofemoral joint complications are frequent and functional outcome is worse than with primary TKR in the general population.

Pretesting is key in the development of patient-reported outcome (PRO) instruments. We describe a mixed-methods approach based on interviews and Rasch measurement methods in the pretesting of the Pressure Ulcer Quality of Life (PU-QOL) instrument. We used cognitive interviews to pretest the PU-QOL in 35 patients with pressure ulcers with the view to identifying problematic items, followed by Rasch analysis to examine response options, appropriateness of the item series and biases due to question ordering (item fit). We then compared findings in an interactive and iterative process to identify potential strengths and weaknesses of PU-QOL items, and guide decision-making about further revisions to items and design/layout. Although cognitive interviews largely supported items, they highlighted problems with layout, response options and comprehension. Findings from the Rasch analysis identified problems with response options through reversed thresholds. The use of a mixed-methods approach in pretesting the PU-QOL instrument proved beneficial for identifying problems with scale layout, response options and framing/wording of items. Rasch measurement methods are a useful addition to standard qualitative pretesting for evaluating strengths and weaknesses of early stage PRO instruments.

Polymethyl methacrylate spacers are commonly used during staged revision knee arthroplasty for infection. In cases with extensive bone loss and ligament instability, such spacers may not preserve limb length, joint stability and motion. We report a retrospective case series of 19 consecutive patients using a custom-made cobalt chrome hinged spacer with antibiotic-loaded cement. The “SMILES spacer” was used at first-stage revision knee arthroplasty for chronic infection associated with a significant bone loss due to failed revision total knee replacement in 11 patients (58%), tumour endoprosthesis in four patients (21%), primary knee replacement in two patients (11%) and infected metalwork following fracture or osteotomy in a further two patients (11%). Mean follow-up was 38 months (range 24–70). In 12 (63%) patients, infection was eradicated, three patients (16%) had persistent infection and four (21%) developed further infection after initially successful second-stage surgery. Above knee amputation for persistent infection was performed in two patients. In this particularly difficult to treat population, the SMILES spacer two-stage technique has demonstrated encouraging results and presents an attractive alternative to arthrodesis or amputation.

We report the first use of an endoprosthetic diaphyseal replacement after the excision of a midshaft radial tumor. We present a rare case of a solitary midshaft radial metastasis in a 72-year-old gentleman who was treated 8 years earlier for primary renal cell carcinoma by radical nephrectomy. Follow-up for this patient was 25 months after implant insertion and at the latest review was pain-free. Functional scores for the elbow (using the Mayo Elbow Performance Score) and the wrist (using the Mayo Wrist Score) were 80 and 60, respectively, both out of 100. Use of a midshaft radial endoprosthesis provides a good functional outcome and symptom relief after extensive tumor resection, with regard to functional outcome and symptom relief.

Various techniques have been described for the treatment of soft tissue extension contracture of the knee. Some involve large exposures, and others can result in a permanent extensor lag. We describe a technique with limited exposure, avoiding transverse incisions in the rectus femoris. Through a midline incision, the extensor expansion is exposed. The rectus femoris is separated from the vastus medialis, lateralis, and intermedius to form a strap-like structure. Vastus intermedius is separated from the patella. If firm, careful manipulation of the knee is unsuccessful, the incisions are extended distally along both sides of the patella and patellar tendon, releasing the extensor mechanism from any underlying heterotopic bone, and further manipulation of the knee is performed. Postoperatively, a rehabilitation program is begun. A good outcome following this technique is described in 3 knees presenting with severe restriction of knee flexion. There were no wound complications and no residual extensor lag.

Obtaining standardised post-operative radiographs following total knee arthroplasty is common practice. Little is known regarding how measurements taken from the initial post-operative radiograph correlate to functional outcome. The initial post-operative radiographs for 110 primary total knee arthroplasties were reviewed retrospectively. Femoral and tibial component alignment was measured by two independent consultant radiologists. Functional outcome was assessed by the Oxford Knee Score pre-operatively and one year post-operatively. Correlation was determined by Pearson correlation analysis. There was no significant correlation between the radiographic measurements with the one year post-operative Oxford Knee Score nor was there significant correlation with the difference in pre-operative and post-operative scores. The initial post-operative radiograph cannot be used as a tool to reliably predict functional outcome at one year.

Over one million patients worldwide are estimated to have a metal-on-metal hip arthroplasty. To improve the management of these patients and reduce surgeon uncertainty regarding decision-making, we designed an Internet-enhanced multidisciplinary team (iMDT) working approach.From August 2012 to April 2014, the iMDT discussed 215 patients with 266 metal-on-metal hip arthroplasties. Of these, 236 primary arthroplasties (132 hip resurfacing and 104 total hip) were analyzed. The remaining thirty cases involved problematic revised hips and were therefore excluded. The possible recommendations of the iMDT were monitoring, further investigation, or surgery. The concordance between the recommendation and the actual management was used to assess the usefulness of this approach in reducing uncertainty in surgeon-level decision-making.The median Oxford Hip Score was 35 (range, 4 to 48), and median cobalt and chromium levels in whole blood were 3.54 ppb (range, 0.18 to 161.46 ppb) and 3.17 ppb (range, 0.20 to 100.67 ppb), respectively. Magnetic resonance imaging revealed abductor muscle atrophy in ninety-two (39%) of the hips and a pseudotumor in eighty (34%). The iMDT recommended monitoring of 146 (61.9%) of the hips, further investigation of thirty (12.7%), and surgery in sixty (25.4%). The actual outcome was concordant with the recommendation in 211 (91.7%) of the hips.Our iMDT approach to the metal-on-metal hip burden combines the tacit knowledge of an expert panel, regulatory guidance, and up-to-date evidence to improve decision-making among surgeons. The high level of concordance between the recommendation and the actual outcome, combined with the feasibility of the methods used, suggest that this method effectively reduces uncertainty among surgeons and may lead to improved patient outcomes.

Clear cell sarcoma of tendons and aponeuroses (CCSTA) is a rare, aggressive soft tissue malignancy, which is found in intimate association with tendon, aponeurosis or fascia. It has not previously been reported in association with intraarticular ligaments. We report the first case of an intraarticular CCSTA, in this case of the anterior cruciate ligament and describe the diagnostic and treatment challenges of intraarticular tumours of the knee.

Objective Osteoarthritis (OA) is a common debilitating disease that results in degeneration of cartilage and bone in the synovial joints. Subtle changes in the molecular structure of the subchondral bone matrix occur and may be associated with cartilage changes. The aim of this study was to explore whether the abnormal molecular changes observed in the matrix of OA subchondral bone can be identified with Raman spectroscopy. Methods Tibial plateaus from patients undergoing total knee replacement for OA (n = 10) were compared with healthy joints from patients undergoing leg amputation (n = 5; sex- and laterality-matched) and with non-OA cadaveric knee specimens (n = 5; age-matched). The samples were analyzed with Raman spectroscopy, peripheral quantitative computed tomography, and chemical analysis to compare changes in defined load-bearing sites in both the medial and lateral compartments. Results OA subchondral bone matrix changes were detected by Raman spectroscopy. Within each cohort, there was no spectral difference in bone matrix chemistry between the medial and lateral compartments, whereas a significant spectral difference (P < 0.001) was observed between the non-OA and OA specimens. Type I collagen chain ratios were normal in the non-OA specimens but were significantly elevated in the OA specimens. Conclusion In comparing the results of Raman spectroscopy with those obtained by other standard techniques, these findings show, for the first time, that subchondral bone changes, or inherent differences, exist in both the medial and lateral (beneath intact cartilage) compartments of OA knees. The development of Raman spectroscopy as a screening tool, based on molecular-specific modifications in bone, would facilitate the identification of clinical disease, including early molecular changes.

The rapid rise in the incidence of failed metal-on-metal hip articulations in recent years has led to many patients requiring complex revision surgery. These failed metal prostheses may produce local metallic debris, which promotes both local and systemic adverse effects. We report an unusual case of failed metal-on-metal resurfacing hip arthroplasty presenting with ipsilateral buttock pain and foot drop 6 months after surgery. After thorough investigations, the metal-on-metal bearing was revised to a metal-on-polyethylene total hip replacement. This resulted in marked improvement in the systemic symptoms, inflammatory marke and metal ion levels postoperatively. However, neither clinical nor neurophysiological sciatic nerve recovery followed. The patient eventually required tendon transfer surgery for her persistent foot drop.

Periprosthetic femoral fractures with long stem implants, poor bone stock and loosening pose a considerable surgical challenge. We describe a reconstruction technique using a custom-made mega-prosthesis, cement-linked to the femoral stem of a well-fixed existing implant. Clinical and radiological outcomes were assessed at our tertiary referral centre. There were 15 patients with a periprosthetic femoral fracture: 5 proximal and 10 distal femoral arthroplasties linked to existing femoral stems. The survival rate was 93.3% at a mean follow-up of 5.3 years (0.5-19.3) with 1 revision. We present a salvage technique with good intermediate-term outcomes for highly selected patients with complex periprosthetic femoral fractures, as another option to conventional fixation methods. Specifically, it allows immediate weight bearing and avoids some of the morbidity of total femoral arthroplasty or amputation.

We have reviewed five adult patients treated with endoprosthetic reconstruction of the proximal radius following resection of non-traumatic lesions. The patients had a mean age of 33.4 years (20 to 60) at the time of surgery and the mean follow-up was 7.6 years (0.8 to 16). Following surgery, all elbows were clinically stable and there was 100% survivorship of the prosthesis. Evaluation of function was assessed clinically and by the Mayo Elbow Performance Score, achieving a mean of 86% (70 to 100). Results at medium-term follow-up are encouraging with regards to elbow stability, implant survivorship and functional outcome.

Disarticulation of the hip in patients with high-grade tumours in the upper thigh results in significant morbidity. In patients with no disease of the proximal soft tissue a femoral stump may be preserved, leaving a fulcrum for movement and weight-bearing. We reviewed nine patients in whom the oncological decision would normally be to disarticulate, but who were treated by implantation of an endoprosthesis in order to create a functioning femoral stump. The surgery was undertaken for chondrosarcoma in four patients, pleomorphic sarcoma in three, osteosarcoma in one and fibrous dysplasia in one. At follow-up at a mean of 80 months (34 to 132), seven patients were alive and free from disease, one had died from lung metastases and another from a myocardial infarction. The mean functional outcome assessment was 50 (musculoskeletal tumor society), 50 and 60 (physical and mental Short-form 36 scores). Implantation of an endoprosthesis into the stump in carefully selected patients allows fitting of an above-knee prosthesis and improves wellbeing and the functional outcome.

With the increased use of metal-on-metal as a bearing surface, complications and side effects are being recognised more frequently. We present a small series of a previously unreported complication, which appears specific to metal-on-metal bearing surface arthroplasties: three cases of infection in the presence of local metal debris and histological features of aseptic lymphocytic vasculitis associated lesions (ALVAL). Each case is associated with significant soft tissue loss and bone destruction to such an extent that pelvic discontinuity has occurred.We postulate that the combination of metal debris, ALVAL and tissue necrosis provides a unique environment for peri-prosthetic bacterial growth and rapid spread of infection.

Several decades of research have shown that lesbian, gay and bisexual (LGB) adults are at high risk for substance use and substance use disorders (SUDs). These problems may often start prior to young adulthood; however, relatively little is known about risk for substance use in LGB adolescents. The primary aims of this paper were to conduct a meta-analysis of the relationship between sexual orientation and adolescent substance use and a systematic review and critique of the methodological characteristics of this literature.Medical and social science journals were searched using Medline and PsychInfo. Studies were included if they tested the relationship between sexual orientation and adolescent substance use. Eighteen published studies were identified. Data analysis procedures followed expert guidelines, and used National Institutes of Health (NIH)-sponsored meta-analysis software.LGB adolescents reported higher rates of substance use compared to heterosexual youth (overall odds ratio = 2.89, Cohen's d = 0.59). Effect sizes varied by gender, bisexuality status, sexual orientation definition and recruitment source. None of the studies tested mediation and only one tested moderation. One employed a matched comparison group design, one used a longitudinal design, and very few controlled for possible confounding variables.The odds of substance use for LGB youth were, on average, 190% higher than for heterosexual youth and substantially higher within some subpopulations of LGB youth (340% higher for bisexual youth, 400% higher for females). Causal mechanisms, protective factors and alternative explanations for this effect, as well as long-term substance use outcomes in LGB youth, remain largely unknown.

The results of the management of 115 patients with intradural spinal tumours are presented. Data was collected retrospectively from the case notes. Tumours were categorized as intramedullary or extramedullary for statistical analysis. Meningioma, schwannoma and ependymoma accounted for 70% of tumours. Complete macroscopic excision was achieved in 84% of extramedullary and 54% of intramedullary tumours. There were two post-operative deaths, one of which was secondary to methacillin-resistant staphylococcus aureus (MRSA) meningitis. Cerebrospinal fluid leak (10%) and meningitis (7%) were the commonest complications. Ninety-six percent of patients with extramedullary tumours improved or remained unchanged on the Frankel scale. In the intramedullary group, 82% remained unchanged or improved after treatment. Pre-operative functional status was a predictor of good post-operative function for intra- and extramedullary tumours and for intramedullary tumours a good post-operative Frankel score predicted long-term survival.

We report the determination of the global fold of human ubiquitin using protein backbone NMR residual dipolar coupling and long-range nuclear Overhauser effect (NOE) data as conformational restraints. Specifically, by use of a maximum of three backbone residual dipolar couplings per residue (Ni-H N i, Ni-C'(i-1), H N i - C'(i-1)) in two tensor frames and only backbone H N -H N NOEs, a global fold of ubiquitin can be derived with a backbone root-mean-square deviation of 1.4 A with respect to the crystal structure. This degree of accuracy is more than adequate for use in databases of structural motifs, and suggests a general approach for the determination of protein global folds using conformational restraints derived only from backbone atoms.

We report a case of severe fixed flexion deformity of the knee, following anterior cruciate ligament (ACL) reconstruction, due to protrusion of the bone block and fixation screw into the knee joint above the tibial tunnel. This was treated successfully after a latent period of 6 years with surgical intervention. This case highlights the importance of critical review of radiographic imaging when faced with a fixed flexion deformity of the knee after ACL surgery and the ability to achieve a good outcome from simple surgical intervention even after a long latent period.

Most secreted eukaryotic proteins are modified by glycosylation, and it has been difficult to solve their structures by crystallographic or NMR techniques because of problems posed by the presence of the carbohydrate. The structure of a chemically deglycosylated form of the human pregnancy hormone, human chorionic gonadotropin (hCG), has been solved by crystallographic methods. Since chemical deglycosylation may have induced changes in the structure, and since it is known that deglycosylated hCG is biologically inactive, the crystallographic structure requires confirmation by NMR techniques. Also, it has not been possible to determine the structures of the isolated subunits, nor the nature of interactions between the carbohydrate side chains and the protein back bone by crystallographic methods. Structural information via NMR techniques can be obtained from proteins in solution if they can be uniformly labeled with 13C and 15N isotopes. We report the first such uniform labeling of a glycoprotein using a universal 13C-and 15N-labeling medium to express 13C, 15N-labeled hCG, suitable for solving the structure in solution of the native, biologically active form of hCG as well as that of its free subunits. The 13C, 15N-labeled recombinant hCG and its separated subunits are shown to be nearly identical to urinary hCG reference preparations on the basis of protein chemical studies, immunochemistry, biological activity, and the capability of isolated hormone subunits to recombine to form biologically active hormone. Mass spectrometric analysis and preliminary NMR studies indicate that the isotopic labeling is uniform and greater than 90% after only two growth passages in the labeling media. One unexpected finding during subunit purification was that lyophilization of glycoproteins from trifluoroacetic acid HPLC buffers may result in the loss of a significant portion of sialic acid.

Summary. We present the results of 34 total hip arthroplasties performed, on haemophiliac patients, between 1983 and 2005. The haematological diagnoses and management are discussed, emphasizing their impact on keeping complication levels to a minimum. The orthopaedic diagnoses and treatment methods are also highlighted, discussing the survivorship and reasons for their failures.