The role of ultrasound in the assessment of post-operative complications following hip arthroplasty.

Hip arthroplasty is one of the most commonly performed orthopedic procedures. Clinicians can be faced with the diagnostic dilemma of the patient presenting with a painful hip following arthroplasty and satisfactory post-operative radiographs. Identifying the cause of symptoms can be challenging and ultrasound is increasingly being utilized in the evaluation of potential soft tissue complications following hip surgery. In this article, we describe the common surgical approaches used during hip arthroplasty as this can influence the nature and location of subsequent complications. A review of the literature is presented along with the imaging appearances frequently encountered when imaging this patient population.

Magnetite: Behavior near the Single-Domain Threshold.

Maximum values for the single-domain threshold d(0) and superpara-magnetic threshold d(8) in pure magnetite are found to be 570+/-50 and 350+/-50 angstroms, respectively. Particles larger than do but smaller than about 0.25 micron have size-dependent saturation remanences and coercive forces like those of multidomain particles, but intense and stable thermoremanent magnetization like that of single-domain particles. The presence of magnetite grains in this size range could account for the essentially single-domain character of stable natural remanence in many volcanic and intrusive rocks.

Monodomain theory: experimental verification.

The Néel thermal-activation theory of remanence in monodomain grains has been verified quantitatively in experiments on four ferrite micropowders and two natural rocks. Magnetization and demagnetization curves of thermal, isothermal, viscous, and anhysteretic remanences can all be predicted with reasonable accuracy when the Neél theory is generalized to include effects of grain interaction. Results with the natural materials indicate that interacting, single-domain grains or regions are the carriers of the magnetically hard natural remanence of some paleomagnetic rocks.

Hematite: intrinsic and defect ferromagnetism.

Both intrinsic (spin-canted) ferromagnetism and defect ferromagnetism occur in hematite. Because defect ferromagnetism is sensitive to structure, it is altered by stress or heating and could give spurious paleomagnetic information. Annealing experiments now suggest that the defect remanence of fine-grain hematites and red sediments, unlike that of single crystals, is magnetically softer than the spin-canted remanence and can be erased by partial demagnetization.

Chemico-Viscous Remanent Magnetization in the Fe3O4-yFe2O3 System.

The chemical remanent magnetization (CRM) acquired when single-domain size magnetite (Fe(3)0(4)) oxidizes to maghemite (gammaFe(2)O(3)) in a 50-microtesla field at a series of 13 temperatures from 1000 to 6560C is of similar intensity to viscous remanent magnetization (VRM) acquired under the same field and temperature conditions by unoxidized magnetite. The remanences of the oxidized and unoxidized phases also have similar resistances to demagnetization. These similarities imply that the remanence of the oxidized material is a chemico-viscous remanent magnetization (CVRM) having some of the characteristics of both classic growth CRM and thermally activated VRM. At low temperatures in partially oxidized grains, VRM of the magnetite core and growth CRM of the maghemite surface layer contribute about equally to CVRM. Near the Curie point, intensity of CVRM increases to a Hopkinson-type peak. High-temperature CVRM is more resistant to demagnetization than the thermoremanent magnetization (TRM) produced from cooling through the Curie point.

Magnetic properties of hydrothermally recrystallized magnetite crystals.

The discrepancy between the magnetic hysteresis properties of magnetite crystals that are precipitated from solution (<0.3 micrometer) and of crushed sifted grains (>0.3 micrometer) is not an inherent property of magnetite but is caused by the highly stressed state of crushed material and by adhering finer fragments. The size trends of magnetic properties exhibited by submicrometer-size precipitated grains continue in the size range from 1 micrometer to 1 millimeter in a set of hydrothermally recrystallized magnetite crystals. Coercive forces of these narrowly sized crystals follow a power law over a wide size range (0.1 micrometer to 1 millimeter) as predicted by theory. Dislocation etch pits show similar dislocation densities for hydrothermally grown (3 x 10(10) meter (-2)) and natural (1 x 10(10) meter(-2)) magnetite crystals. Hysteresis parameters of hydrothermally grown crystals are similar to those of natural crystals but are about one-fifth of those for crushed grains.

What is the significance of a positive Propionibacterium acnes culture around a joint replacement?

The purpose of this study was to show the significance of a positive Propionibacterium acnes sample around a joint replacement. Records from the microbiology laboratory data over a 3-year period were reviewed to identify patients with prosthetic joints from whom Propionibacterium acnes was isolated at least once. The medical records of all those patients were retrieved and the demographic, clinical, microbiological and haematological data were collected and examined. The preoperative values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were recorded. Fifty patients underwent a routine revision of a joint arthroplasty; six patients had a joint aspiration. Only one patient had further revision surgery for infection. The preoperative values of ESR and CRP were very variable. The presence of a positive sample around a joint arthroplasty is of uncertain significance. Further studies are needed in order to establish uniform criteria for the diagnosis of infection caused by Propionibacterium acnes.

Risk factors for failure of the 36 mm metal-on-metal Pinnacle total hip arthroplasty system: a retrospective single-centre cohort study.

AIMS: To determine ten-year failure rates following 36 mm metal-on-metal (MoM) Pinnacle total hip arthroplasty (THA), and identify predictors of failure. PATIENTS AND METHODS: We retrospectively assessed a single-centre cohort of 569 primary 36 mm MoM Pinnacle THAs (all Corail stems) followed up since 2012 according to Medicines and Healthcare Products Regulation Agency recommendations. All-cause failure rates (all-cause revision, and non-revised cross-sectional imaging failures) were calculated, with predictors for failure identified using multivariable Cox regression. RESULTS: Failure occurred in 97 hips (17.0%). The ten-year cumulative failure rate was 27.1% (95% confidence interval (CI) 21.6 to 33.7). Primary implantation from 2006 onwards (hazard ratio (HR) 4.30; 95% CI 1.82 to 10.1; p = 0.001) and bilateral MoM hip arthroplasty (HR 1.59; 95% CI 1.03 to 2.46; p = 0.037) predicted failure. The effect of implantation year on failure varied over time. From four years onwards following surgery, hips implanted since 2006 had significantly higher failure rates (eight years 28.3%; 95% CI 23.1 to 34.5) compared with hips implanted before 2006 (eight years 6.3%; 95% CI 2.4 to 15.8) (HR 15.2; 95% CI 2.11 to 110.4; p = 0.007). CONCLUSION: We observed that 36 mm MoM Pinnacle THAs have an unacceptably high ten-year failure rate, especially if implanted from 2006 onwards or in bilateral MoM hip patients. Our findings regarding implantation year and failure support recent concerns about the device manufacturing process. We recommend all patients undergoing implantation since 2006 and those with bilateral MoM hips undergo regular investigation, regardless of symptoms. Cite this article: Bone Joint J 2017;99-B:592-600.

Can blood metal ion levels be used to identify patients with bilateral Birmingham Hip Resurfacings who are at risk of adverse reactions to metal debris?

AIMS: We investigated whether blood metal ion levels could effectively identify patients with bilateral Birmingham Hip Resurfacing (BHR) implants who have adverse reactions to metal debris (ARMD). PATIENTS AND METHODS: Metal ion levels in whole blood were measured in 185 patients with bilateral BHRs. Patients were divided into those with ARMD who either had undergone a revision for ARMD or had ARMD on imaging (n = 30), and those without ARMD (n = 155). Receiver operating characteristic analysis was used to determine the optimal thresholds of blood metal ion levels for identifying patients with ARMD. RESULTS: The maximum level of cobalt or chromium ions in the blood was the parameter which produced the highest area under the curve (91.0%). The optimal threshold for distinguishing between patients with and without ARMD was 5.5 µg/l (83.3% sensitivity, 88.4% specificity, 58.1% positive and 96.5% negative predictive values). Similar results were obtained in a subgroup of 111 patients who all underwent cross-sectional imaging. Between 3.2% and 4.3% of patients with ARMD were missed if United Kingdom (7 µg/l) and United States (10 µg/l) authority thresholds were used respectively, compared with 2.7% if our implant specific threshold was used, though these differences did not reach statistical significance (p ≥ 0.248). CONCLUSION: Patients with bilateral BHRs who have blood metal ion levels below our implant specific threshold were at low-risk of having ARMD. Cite this article: Bone Joint J 2016;98-B:1455-62.

The utility of repeat ultrasound imaging in the follow-up of metal-on-metal hip arthroplasty patients.

INTRODUCTION: We assessed changes in metal-on-metal hip arthroplasties (MoMHAs) after repeat ultrasound examination. METHODS: This retrospective, single-centre cohort study involved all patients undergoing two ultrasound examinations of the same MoMHA. Between 2010 and 2014, 96 ultrasound examinations were performed in 48 MoMHAs (mean time between scans = 1.1 years). A radiologist assigned each scan to one of four grades and measured volumes of any solid/cystic masses. Changes in grade and lesion volume between scans were analysed. RESULTS: Change in grade between scans was significant (p=0.012); 27% (n=13) of MoMHAs increased in grade, 67% (n=32) had no grade change, and 6% (n=3) decreased in grade. The mean increase in lesion volume was 24.2cm(3) by the second scan, and was significant (p=0.023). Evidence of progression in findings was observed in 54% (26/48) of MoMHAs. Of patients with normal scans initially, 44% (8/18) developed abnormalities. No factors (including blood metal ion concentrations and cup position) were associated significantly with progression of ultrasound findings. CONCLUSIONS: Repeat ultrasound in MoMHA patients demonstrated that findings frequently progress in the short-term. Therefore, regular surveillance of MoMHA patients is important, with ultrasound representing an effective investigation for identifying the development and progression of lesions.

CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.

PURPOSE: The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS: For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS: The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION: These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.

ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score

A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer.

BACKGROUND: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-ß2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

Colonic adenocarcinoma associated ectopic ACTH secretion: a case history.

A 57-year-old woman developed features of Cushing's syndrome after resection of a Duke's C adenocarcinoma of the sigmoid colon. Biochemical and endocrine investigation indicated ectopic production of adrenocorticotrophic hormone (ACTH) as the cause for her condition. Hepatic metastases were detected by computed tomography (CT) scan. Histology of the original tumour displayed neuroendocrine characteristics but no definite evidence of ACTH synthesis. Treatment was instituted to control her hypercortisolism, and chemotherapy initiated to reduce the production of ectopic hormone. A clinical, biochemical and radiological response was obtained with complete resolution of her Cushing's syndrome. The tumour relapsed after several months with distant metastases, but no further endocrine abnormality was noted. A review of ectopic ACTH producing adenocarcinoma is given along with a discussion of the major pathological and therapeutic features of the case.

Phase I/II study of gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results.

Sixty-six patients with advanced non-small cell lung cancer have been entered into a phase I/II study of a combination of gemcitabine and cisplatin. An initial phase I portion of the study has been completed, and 16 patients have been entered using a fixed dose of gemcitabine 1,000 mg/m2 as a 30-minute intravenous infusion weekly for 3 weeks. Cisplatin was administered on day 15 following gemcitabine with appropriate prehydration and posthydration. The study was designed to allow for sequential groups of three patients to receive three dose levels of cisplatin (60 mg/m2, 75 mg/ m2, and 100 mg/m2). Dose modification and patient numbers were to be increased at any dose level if significant toxicity was observed. The regimen was well tolerated at all doses, and the final level of cisplatin 100 mg/m2 was expanded to 10 patients before the phase II portion was opened. Neutropenia (World Health Organization grade 4 in three patients) and thrombocytopenia (grade 3 or 4 in five patients) were the main hematologic toxicities recorded. These episodes were brief and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients, but was no worse than would be expected from cisplatin alone. Alopecia, when it occurred, was minimal (no hair loss in 10 patients and grade 1 or 2 in six patients). No significant renal toxicity or neurotoxicity was seen. A phase II study with cisplatin 100 mg/m2 and gemcitabine 1,000 mg/m2 has been opened, and to date 43 patients are evaluable for response. Eighteen (42%) patients have achieved partial remissions. The study will close when 50 evaluable patients have been entered.

CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens.

We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.

Bioavailability of subcutaneous 5-fluorouracil: a case report.

The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to the local skin toxicity.

Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature.

Lymphomas account for 2-5% of all oral malignancies and are the third most common in this site. This case report appears to be the first in the world literature describing spontaneous regression in the oral cavity of a subset of non-Hodgkins lymphomas known as Ki-1 anaplastic large cell lymphomas (ALCL). Ki-1 ALCL account for 2-7% of all non-Hodgkins lymphomas and the clinical presentation is variable; they may arise de novo or in the setting of a separate primary lymphoma and commonly present in the extra-nodal location. Disease severity is also variable with waxing and waning lesions at one extreme which may spontaneously regress to bone marrow involvement in around 12% of cases. This case is especially interesting since the patient is a farmer, given the recent evidence that there may be a link between non-Hodgkins lymphoma and this occupation.

A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer.

AIM: The aim of this study was to evaluate the activity of the combination of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer (SCLC). Patients with good prognosis disease were included who were not medically fit to tolerate conventional chemotherapy. Activity was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Fifty-eight patients, 37 men and 21 women, with histologically or cytologically confirmed SCLC, who had bi-dimensionally measurable disease, with ECOG performance status > or = 2, with adequate haematological, hepatic and renal function received first-line chemotherapy with carboplatin (AUC x 5) day 1 and vinorelbine (30 mg/m2) days 1 and 8 of a 28-day cycle. Response was assessed after every two cycles of chemotherapy, with patients receiving a maximum of six cycles of treatment. RESULTS: The combination of carboplatin and vinorelbine is an active regimen in the treatment of SCLC, with an overall intention-to-treat response rate of 55% [95% confidence interval (CI): 42-68%] with six (10%) of patients having a complete response. Median time to progression was 18 weeks (95% CI: 15-21 weeks). Median overall survival was 26 weeks (95% CI: 21-31 weeks). Ten patients failed to complete two cycles of treatment, and were not evaluable for response for the following reasons: septic death (1 neutropaenic, 1 no myelotoxicity), non-toxic death (1 tumour eroded through the pulmonary artery, 1 ischaemic heart disease) ischaemic heart disease (1) and patient decision (5). There were a total of three toxic deaths all sepsis-complicating neutropaenia. Forty-four (76%) patients experienced grade 3 or 4 neutropaenia, six (11%) grade 3 or 4 thrombocytopaenia, 10 (13%) grade 3 lethargy, three (5%) grade 3 nausea and two (3%) grade 3 diarrhoea. CONCLUSIONS: The combination of carboplatin and vinorelbine is active against SCLC but the toxicity profile in this group of patients suggests that further evaluation is not appropriate.