Definition and validation of a system for classifying the undersized Corail femoral stem in total hip arthroplasty.

INTRODUCTION: The uncemented total hip arthroplasty relies on a secure initial fixation of the femoral stem to achieve osseointegration. Undersizing of the femoral implant compromises this. Surgeons routinely review postoperative radiographs to assess appropriate sizing, but existing methods of assessment lack standardisation. We present a system of accurately and reliably classifying radiological undersizing, which will help us better understand the factors that might have led to undersizing. AIM: To describe and evaluate a classification system for assessing radiological undersizing of the uncemented stem in hip arthroplasty. METHOD: We conducted a retrospective review of 1,337 consecutive hip arthroplasties using the Corail stem. Two independent investigators reviewed post-operative radiographs and classified them as either appropriately sized or undersized. Undersized stems were sub-categorised into four subtypes: uniformly undersized, varus undersized, valgus undersized or 'cocktail-glass' undersized. Inter- and intra-observer agreement was determined. The accuracy of our classification system was validated by comparison with digital re-templating. We further assessed patient demographics and stem size in relation to sizing. RESULTS: 1 in 5 cases (19.75%) were deemed radiologically undersized. The commonest subtypes of undersizing were uniformly (47%) and varus (39%) undersized. When assessing sizing and subtype categorisation, inter-observer agreement was 89-92% and intra-observer agreement 86%. Classification decisions showed 92% and 97% accuracy for uniformly undersizing and varus undersizing respectively when validated against digital re-templating. Age, gender and smaller stem size were significantly associated with radiological undersizing. The Corail KLA model (125° neck) was found to have a higher incidence of stems undersized in varus. CONCLUSIONS: This study describes and validates a classification system for the analysis of radiological undersizing.

Pyomyositis of Gluteus medius: A case report and review of the literature.

INTRODUCTION: We present a case of 12 year old boy presented with right hip pain, fever and antalgic gait. Inflammatory markers were raised at presentation. The pelvic radiograph and ultra sound scan of right hip joint did not detect any abnormality. The Magnetic Resonance Imaging (MRI) scans revealed inflammatory oedema in the right gluteus medius muscle. He was treated with intravenous Flucloxacillin for 10 days and later 6 weeks of oral Flucloxacillin. At the 6 weeks follow up patient was asymptomatic with normal gait. MRI at 6 weeks did not show any fluid collection in gluteus medius. CONCLUSION: Pyomyositis is rare in temperate countries. It must be considered as one of the differential diagnosis in a child presenting with hip pain, fever and raised inflammatory markers.

Blood Metal Ion Thresholds to Identify Patients with Metal-on-Metal Hip Implants at Risk of Adverse Reactions to Metal Debris: An External Multicenter Validation Study of Birmingham Hip Resurfacing and Corail-Pinnacle Implants.

BACKGROUND: The authors of recent studies have reported newly devised implant-specific blood metal ion thresholds to predict adverse reactions to metal debris (ARMD) in patients who have undergone unilateral or bilateral metal-on-metal (MoM) hip arthroplasty. These thresholds were most effective for identifying patients at low risk of ARMD. We investigated whether these newly devised blood metal ion thresholds could effectively identify patients at risk of ARMD after MoM hip arthroplasty in an external cohort of patients. METHODS: We performed a validation study involving 803 MoM hip arthroplasties (323 unilateral Birmingham Hip Resurfacing [BHR], 93 bilateral BHR, and 294 unilateral Corail-Pinnacle implants) performed in 710 patients at 3 European centers. All patients underwent whole-blood metal ion sampling, and were divided into 2 groups: those with ARMD (leading to revision or identified on imaging; n = 75) and those without ARMD (n = 635). Previously devised implant-specific blood metal ion thresholds (2.15 µg/L of cobalt for unilateral BHR; 5.5 µg/L for the maximum of either cobalt or chromium for bilateral BHR; and 3.57 µg/L of cobalt for unilateral Corail-Pinnacle implants) were applied to the validation cohort, and receiver operating characteristic curve analysis was used to establish the discriminatory characteristics of each threshold. RESULTS: The area under the curve, sensitivity, specificity, and positive and negative predictive values for the ability of each implant-specific threshold to distinguish between patients with and without ARMD were, respectively, 89.4% (95% confidence interval [CI] = 82.8% to 96.0%), 78.9%, 86.7%, 44.1%, and 96.9% for unilateral BHR; 89.2% (CI = 81.3% to 97.1%), 70.6%, 86.8%, 54.5%, and 93.0% for bilateral BHR; and 76.9% (CI = 63.9% to 90.0%), 65.0%, 85.4%, 24.5%, and 97.1% for unilateral Corail-Pinnacle implants. Using the implant-specific thresholds, we missed 20 patients with ARMD (2.8% of the patients in this series). We missed more patients with ARMD when we used the fixed thresholds proposed by regulatory authorities: 35 (4.9%) when we used the U.K. threshold of 7 µg/L for both cobalt and chromium (p = 0.0003), 21 (3.0%) when we used the U.S. threshold of 3 µg/L for both cobalt and chromium (p = 1.0), and 46 (6.5%) when we used the U.S. threshold of 10 µg/L for both cobalt and chromium (p < 0.0001). CONCLUSIONS: This external multicenter validation study confirmed that patients with blood metal ion levels below new implant-specific thresholds have a low risk of ARMD after MoM hip arthroplasty. Using these implant-specific thresholds, we missed fewer patients with ARMD compared with when the thresholds currently proposed by regulatory authorities were used. We therefore recommend using implant-specific blood metal ion thresholds when managing patients who have undergone MoM hip arthroplasty. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bilateral transient osteoporosis of the hip in a 20-year-old man.

Transient osteoporosis is a rare musculoskeletal condition that has been reported in pregnant women and middle-aged men. We present a bilateral case in a young man. A 20-year-old man presented with spontaneous onset left hip pain. Investigations excluded other differential diagnoses such as infection or fracture. The pain resolved completely; 6 months later the patient presented with a similar episode of pain in the contralateral hip. This also resolved spontaneously. Doctors need to be aware of the possibility of spontaneous onset musculoskeletal pain due to transient osteoporosis occurring in young men. The typical presentation is of spontaneous onset progressive pain, often affecting the hip. Other pathology must be excluded. The investigation of choice is MRI, and the treatment is simple analgesia.

Management of acute anterior shoulder dislocation.

Shoulder dislocation is the most common large joint dislocation in the body. Recent advances in radiological imaging and shoulder surgery have shown the potential dangers of traditional reduction techniques such as the Kocher's and the Hippocratic methods, which are still advocated by many textbooks. Many non-specialists continue to use these techniques, unaware of their potential risks. This article reviews the clinical and radiographic presentation of dislocation; some common reduction techniques; their risks and success rate; analgesia methods to facilitate the reduction; and postreduction management. Many textbooks advocate methods that have been superceded by safer alternatives. Trainees should learn better and safer relocation methods backed up by the current evidence available.

Blood loss following total knee replacement is reduced when using computer-assisted versus standard methods.

Perioperative blood loss was compared in 136 patients (2 groups of 68 patients) who underwent total knee arthroplasty (TKA). Blood loss was significantly lower when using a computer-navigated technique in comparison to a method employing intramedullary femoral rods. Total blood loss was calculated from body weight, height and haematocrit change, using a model that has been shown to reliably estimate true blood loss. Average total blood loss was 1362 ml in the standard TKA group, and 1137 ml in the computer navigated TKA group. This difference was statistically significant (p = 0.016). This study, as compared to previous papers assessing the effects of navigation, used a larger sample size and a more reliable method of assessing blood loss, which takes account of "hidden" losses, and confirms their findings.

Reducing blood loss in primary knee arthroplasty: a prospective randomised controlled trial of tranexamic acid and fibrin spray.

A prospective, randomised controlled trial compared the effects of two medications intended to reduce blood loss from total knee arthroplasty. Patients were randomised to one of the following three treatment groups: 10mg/kg tranexamic acid at given at induction of anaesthesia, 10 ml of fibrin spray administered topically during surgery, or to a control group receiving neither treatment. Sixty six patients underwent elective cemented total knee arthroplasty; computer navigation was used in all cases. There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups (p=0.181). There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups(p=0.181). The fibrin spray led to a significant reduction in blood loss compared to control (p=0.007). The effect of tranexamic acid did not reach significance (p=0.173). We conclude that fibrin spray was effective in reducing blood loss but that with a study of this power, we were unable to detect an effect of tranexamic acid in cemented navigated total knee replacement at the dose used.

Reduction of blood loss in primary hip arthroplasty with tranexamic acid or fibrin spray.

BACKGROUND AND PURPOSE: Previous studies have shown that either fibrin spray or tranexamic acid can reduce blood loss at total hip replacement, but the 2 treatments have not been directly compared. We therefore conducted a randomized, controlled trial. PATIENTS AND METHODS: In this randomized controlled trial we compared the effect of tranexamic acid and fibrin spray on blood loss in cemented total hip arthroplasty. 66 patients were randomized to 1 of 3 parallel groups receiving (1) a 10 mg/kg bolus of tranexamic acid prior to surgery, (2) 10 mL of fibrin spray during surgery, or (3) neither. All participants except the surgeon were blinded as to treatment group until data analysis was complete. Blood loss was calculated from preoperative and postoperative hematocrit. RESULTS: Neither active treatment was found to be superior to the other in terms of overall blood loss. Losses were lower than those in the control group, when using either tranexamic acid (22% lower, p = 0.02) or fibrin spray (32% lower, p = 0.02). INTERPRETATION: We found that the use of tranexamic acid at induction, or topical fibrin spray intraoperatively, reduced blood loss compared to the control group. Blood loss was similar in the fibrin spray group and in the tranexamic acid group. ClinicalTrials.gov identifier: NCT00378872. EudraCT identifier: 2006-001299-19. Regional Ethics Committee approval: 06/S0703/55, granted June 6, 2006.

Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination.

Multiple regulatory mechanisms control the activity of the protein serine/threonine phosphatase 2A catalytic subunit (PP2Ac), including post-translational modifications and its association with regulatory subunits and interacting proteins. Alpha4 is a PP2Ac-interacting protein that is hypothesized to play a role in PP2Ac ubiquitination via its interaction with the E3 ubiquitin ligase Mid1. In this report, we show that alpha4 serves as a necessary adaptor protein that provides a binding platform for both PP2Ac and Mid1. We also identify a novel ubiquitin-interacting motif (UIM) within alpha4 (amino acid residues 46-60) and analyze the interaction between alpha4 and ubiquitin using NMR. Consistent with other UIM-containing proteins, alpha4 is monoubiquitinated. Interestingly, deletion of the UIM within alpha4 enhances its association with polyubiquitinated proteins. Lastly, we demonstrate that addition of wild-type alpha4 but not an alpha4 UIM deletion mutant suppresses PP2Ac polyubiquitination. Thus, the polyubiquitination of PP2Ac is inhibited by the UIM within alpha4. These findings reveal direct regulation of PP2Ac polyubiquitination by a novel UIM within the adaptor protein alpha4.

Targeting protein serine/threonine phosphatases for drug development.

With the recent clinical success of drugs targeting protein kinase activity, drug discovery efforts are focusing on the role of reversible protein phosphorylation in disease states. The activity of protein phosphatases, enzymes that oppose protein kinases, can also be manipulated to alter cellular signaling for therapeutic benefits. In this review, we present protein serine/threonine phosphatases as viable therapeutic targets, discussing past successes, current challenges, and future strategies for modulating phosphatase activity.

"About a cupful"--a prospective study into accuracy of volume estimation by medical and nursing staff.

In this prospective study, medical and nursing health care professionals were asked to visually estimate various fluid volumes. The aims were to assess overall accuracy, and to identify factors that caused error. The effects of fluid volume, colour and clinical experience were analysed. 152 doctors and nurses were shown a selection of containers filled with five different volumes of fluid, each presented in three different colours. Subjects recorded their estimates of volume by filling in a questionnaire. There was considerable variation in accuracy between subjects. Very large standard deviations were noted, and some subjects were found to over-report, to a maximum of 700%. Nurses were more accurate than doctors (p=0.0003). Nurses' accuracy was influenced by fluid colour but not volume, whereas the opposite was true for doctors. Doctors with more than 20 years' clinical experience significantly overestimated volumes compared to their younger colleagues. This effect was not seen with the nursing group. We conclude that visual estimation is unreliable, and recommend against using visual estimation in clinical practice.

An automated fluorescence-based method for continuous assay of PP2A activity.

Protein serine/threonine phosphatase (PP2A) is a major cellular enzyme implicated in the control of numerous signaling processes. The accurate measurement of PP2A activity in crude cell lysates, immune complexes, and purified preparations provides insight into the function and regulation of this essential enzyme, which, in turn, can lead to a better understanding of the signaling pathways that it modulates. The method presented here utilizes 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) and a FLEXstation for the continuous measure of PP2A activity associated with many different protein preparations. This automated fluorescence-based assay offers several distinct advantages over colorimetric and radioactive assays of phosphatase activity including (1) decreased substrate preparation time, (2) real-time kinetic data, (3) high sensitivity, and (4) the capability to analyze a wide variety of phosphatases.

Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein.

The protein serine/threonine phosphatase (PP) type 2A family consists of three members: PP2A, PP4, and PP6. Specific rabbit and sheep antibodies corresponding to each catalytic subunit, as well as a rabbit antibody recognizing all three subunits, were utilized to examine the expression of these enzymes in select rat tissue extracts. PP2A, PP4, and PP6 catalytic subunits (PP2A(C), PP4(C), and PP6(C), respectively) were detected in all rat tissue extracts examined and exhibited some differences in their levels of expression. The expression of alpha4, an interacting protein for PP2A family members that may function downstream of the target of rapamycin (Tor), was also examined using specific alpha4 sheep antibodies. Like the phosphatase catalytic subunits, alpha4 was ubiquitously expressed with particularly high levels in the brain and thymus. All three PP2A family members, but not alpha4, bound to the phosphatase affinity resin microcystin-Sepharose. The phosphatase catalytic subunits were purified to apparent homogeneity (PP2A(C) and PP4(C)) or near homogeneity (PP6(C)) from bovine testes soluble extracts following ethanol precipitation and protein extraction. In contrast to PP2A(C), PP4(C) and PP6(C) exhibited relatively low phosphatase activity towards several substrates. Purified PP2A(C) and native PP2A in cellular extracts bound to GST-alpha4, and co-immunoprecipitated with endogenous alpha4 and ectopically expressed myc-tagged alpha4. The interaction of PP2A(C) with alpha4 was unaffected by rapamycin treatment of mammalian cells; however, protein serine/threonine phosphatase inhibitors such as okadaic acid and microcystin-LR disrupted the alpha4/PP2A complex. Together, these findings increase our understanding of the biochemistry of alpha4/phosphatase complexes and suggest that the alpha4 binding site within PP2A may include the phosphatase catalytic domain.