Clinical impact of 99mTc-HDP SPECT/CT imaging as standard workup for foot and ankle osteoarthritis.

Objective: The primary aim of this study was to assess to what extent 99mTc-HDP Single photon emission computed tomography/computed tomography (SPECT/CT) will lead to change of diagnosis and treatment, in patients with suspected foot and ankle osteoarthritis (OA). Secondary aim was to assess the intraobserver variability. Methods: Retrospectively 107 patients, with suspected foot and/or ankle OA of which a SPECT/CT was made, were included for analysis. All the clinical and radiological data were randomized and blinded before being scored by one experienced orthopaedic surgeon. Firstly, based on the clinical data and conventional radiographs, a diagnosis and treatment plan was scored. Secondly, the observer accessed the SPECT/CT and could change the diagnosis and treatment plan. Additionally, the intraobserver reliability was determined by data of 18 patients that were added in twofold to the dataset, without awareness of the observer and by calculating the κ values. Results: The diagnosis changed in 53% (57/107) and treatment plans changed in 26% (28/107) of the patients. Intraobserver reliability for the conventional workup was k = 0.54 (moderate strength of agreement), compared to k = 0.66 (substantial strength of agreement) when SPECT/CT data were added. Conclusions: This study describes the influence of SPECT/CT on diagnosis and treatment plans in patients with suspected symptomatic OA. Also, it shows SPECT/CT leads to a higher intraobserver variability. We believe SPECT/CT has a promising role in the workup for foot and ankle OA. Advances in knowledge: In addition to what was found in complex foot and ankle cases, this study shows that in patients with non-complex foot and ankle problems, SPECT/CT has a substantial influence on the diagnosis (and subsequent treatment plan).

Duloxetine in OsteoArthritis (DOA) study: effects of duloxetine on pain and function in end-stage hip and knee OA - a pragmatic enriched randomized controlled trial.

BACKGROUND: Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms. OBJECTIVES: Assess the efficacy of an 8-week duloxetine treatment compared to usual care in end-stage knee and hip OA patients with a level of centralized pain. DESIGN: Pragmatic, enriched, open-label RCT. METHODS: Patients were randomized to duloxetine or to care-as-usual. Primary outcome was pain in the index joint, measured with the pain domain of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS). The intention-to-treat principle was used, with mixed-model repeated measures to analyze the effect. RESULTS: One hundred eleven patients were randomized. Nearly 44% felt much to very much better after duloxetine usage compared to 0% in the care-as-usual group (p < 0.001). The duloxetine group scored 11.3 points (95%CI: 5.8, 16.8) better on the pain domain of the KOOS/HOOS (p < 0.001). Knee patients improved significantly more than hip patients (18.7 [95%CI: 11.3, 26.1] versus 6.0 [95%CI: - 2.6, 14.5] points better). CONCLUSIONS: Adding duloxetine treatment seems to be beneficial for end-stage knee OA patients with neuropathic-like symptoms (at risk of CS). End stage Hip OA patients seem to be nonresponsive to duloxetine. TRIAL REGISTRATION: Dutch Trial Registry with number NTR 4744 (15/08/2014) and in the EudraCT database with number 2013-004313-41 .

Duloxetine in OsteoArthritis (DOA) study: study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty.

INTRODUCTION: Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree of central sensitisation (CS) is associated with poorer postoperative outcomes and residual pain. It is thus hypothesised that preoperative treatment of CS could enhance postoperative outcomes. Duloxetine has been shown to be effective for several chronic pain syndromes, including knee osteoarthritis (OA), in which CS is most likely one of the underlying pain mechanisms. This study aims to evaluate the postoperative effects of preoperative screening and targeted duloxetine treatment of CS on residual pain compared with care-as-usual. METHODS AND ANALYSIS: This multicentre, pragmatic, prospective, open-label, randomised controlled trial includes patients with idiopathic hip/knee OA who are on a waiting list for primary THA/TKA. Patients at risk for CS will be randomly allocated to the preoperative duloxetine treatment programme group or the care-as-usual control group. The primary end point is the degree of postoperative pain 6 months after THA/TKA. Secondary end points at multiple time points up to 12 months postoperatively are: pain, neuropathic pain-like symptoms, (pain) sensitisation, pain catastrophising, joint-associated problems, physical activity, health-related quality of life, depressive and anxiety symptoms, and perceived improvement. Data will be analysed on an intention-to-treat basis. ETHICS AND DISSEMINATION: The study is approved by the local Medical Ethics Committee (METc 2014/087) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard (GCP), and in compliance with the Medical Research Involving Human Subjects Act (WMO). TRIAL REGISTRATION NUMBER: 2013-004313-41; Pre-results.

Chevron versus Mitchell osteotomy in hallux valgus surgery: a comparative study.

Good clinical results have been reported for chevron and Mitchell osteotomies in mild hallux valgus (HV). The primary aim of the present study was to compare first metatarsal shortening after chevron and Mitchell osteotomies in HV. The secondary outcome measures were the degree of valgus correction, metatarsalgia, and patient satisfaction. A total of 84 patients were included in the present study and were treated from 2005 to 2007; 42 patients were in each group. The outcome measurements-first metatarsal length, HV angle, 1-2 intermetatarsal angle, satisfaction, and metatarsalgia-were taken preoperatively and at follow-up. The Mitchell osteotomy resulted in a significantly larger decrease in the first metatarsal length. No significant difference in transfer metatarsalgia was found. Approximately 30% of patients were mildly or not satisfied after HV surgery. Mitchell osteotomy leads to a larger decrease in the first metatarsal length. Patients with metatarsalgia performed poorly, and no significant differences in metatarsalgia were found. Preventing postoperative metatarsalgia is important for a successful outcome after HV surgery.

Osteotomy for medial compartment arthritis of the knee using a closing wedge or an opening wedge controlled by a Puddu plate. A one-year randomised, controlled study.

A prospective, randomised, controlled trial compared two different techniques of high tibial osteotomy with a lateral closing wedge or a medial opening wedge, stabilised by a Puddu plate. The clinical outcome and radiological results were examined at one year. The primary outcome measure was the achievement of an overcorrection of valgus of 4 degrees . Secondary outcome measures were the severity of pain (visual analogue scale), knee function (Hospital for Special Surgery score), and walking distance. Between January 2001 and April 2004, 92 patients were randomised to one or other of the techniques. At follow-up at one year the post-operative hip-knee-ankle angle was 3.4 degrees (+/- 3.6 degrees SD) valgus after a closing wedge and 1.3 degrees (+/- 4.7 degrees SD) of valgus after an opening wedge. The adjusted mean difference of 2.1 degrees was significant (p = 0.02). The deviation from 4 degrees of valgus alignment was 2.7 degrees (+/- 2.4 degrees SD) in the closing wedge and 4.0 degrees (+/- 3.6 degrees sd) in the opening-wedge groups. The adjusted mean difference of 1.67 degrees was also significant (p = 0.01). The severity of pain, knee score and walking ability improved in both groups, but the difference was not significant. Because of pain, the staples required removal in 11 (23%) patients in the closing-wedge group and a Puddu plate was removed in 27 (60%) patients in the opening-wedge group. This difference was significant (p < 0.001). We conclude that closing-wedge osteotomy achieves a more accurate correction with less morbidity, although both techniques had improved the function of the knee at one year after the procedure.

Anterior opening wedge osteotomy of the proximal tibia for anterior knee pain in idiopathic hyperextension knees.

We analysed 20 patients with 24 knees affected by idiopathic genu recurvatum who were treated with an anterior opening wedge osteotomy of the proximal tibia because of anterior knee pain. We managed to attain full satisfaction in 83% of the patients with a mean follow-up of 7.4 years. The mean Hospital for Special Surgery score was 90.3 (range 70.5-99.5), and the mean Knee Society score score was 94.6 (70-100) for function and 87.7 (47-100) for pain. The mean Western Ontario and McMaster University Osteoarthritis Index score for knee function was 87.5 (42-100), for stiffness 82.8 (25-100) and for pain 87.3 (55-100). Radiographs showed a significant increase in posterior tibial slope of 9.4 deg and a significant decrease of patellar height according to the Blackburne-Peel method of 0.16 postoperatively. No cases of non-union, deep infection or compartment syndrome were seen. No osteoarthritic changes in the lateral or medial knee compartment were found with more than 5 years' follow-up in 16 patients with 19 affected knees. Three out of the four dissatisfied patients had a patella infera which led to patellofemoral complaints. One patient in the study underwent a secondary superior displacement of the patella with excellent results. We conclude that in a selected group of patients with idiopathic genu recurvatum and anterior knee pain an opening wedge osteotomy of the proximal tibia can be beneficial.

Brace treatment for osteoarthritis of the knee: a prospective randomized multi-centre trial.

OBJECTIVE: To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or valgus alignment, respectively. DESIGN: This multi-centre randomized controlled trial (performed 2001-2003) studies the additive effect of a brace intended to reduce load in conservative treatment of unicompartmental OA of the knee. SETTING: Orthopedic department of a university medical centre and of one general hospital. The follow-up was 12 months. PATIENTS: 117 patients with unicompartmental OA of the knee. Intervention group (n=60) comprising conservative treatment with additional brace treatment and a control group (n=57) comprising conservative treatment alone. PRIMARY OUTCOME MEASURES: Pain severity and knee function score. SECONDARY OUTCOME MEASURES: Walking distance and quality of life. ANALYSIS: Multiple linear regression models according to the intention-to-treat-principle were used to assess outcome differences for the entire group of patients. In addition, we performed explorative subgroup analyses on primary overall outcomes stratified for alignment, degree of OA, origin of OA, and age. RESULTS: Although the primary outcome measures were improved in the intervention group in comparison with the controls at each assessment point, the differences reached only borderline significance. The reported walking distances at 3 months, 12 months and overall were significantly longer in the brace group (P=0.03, P=0.04 and P=0.02, respectively). Subgroup analysis showed a better effect in the varus group, in patients with severe OA, in patients with secondary OA and in patients younger then 60 years. In total 25 patients in the brace group and 14 in the control group changed their initial treatment, mostly (74%) because of a lack of beneficial effect. CONCLUSIONS: The results indicate that a brace intended to reduce load shows small effects in patients with unicompartmental OA. However, many patients do not adhere in the long run to this kind of conservative treatment.

Selective avoidance of postoperative locoregional radiotherapy in breast cancer seems to be justified.

OBJECTIVE: To try and reduce the amount of routine postoperative radiotherapy that we prescribed without causing an unacceptable rise in locoregional recurrences. DESIGN: Retrospective study. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 836 women who were treated for breast cancer between January 1980 and December 1989. INTERVENTIONS: These 836 had been treated by modified radical mastectomy (n = 534), excision of the tumour and axillary dissection (n = 279), lumpectomy (n = 15), or total mastectomy (n = 8). In December 1984 we stopped giving routine postoperative irradiation to women with T1 or T2 tumours unless there was any doubt about the operative specimen. MAIN OUTCOME MEASURES: The rate of locoregional recurrence 1985-9 compared with that from 1980-December 1984. RESULTS: Only 1 patient of 836 had a clinically detectable recurrence in the internal mammary chain. There were only 2 recurrences in the 235 axillas that had not been irradiated. CONCLUSION: By a process of careful selection of patients for locoregional irradiation, the number of fields of irradiation given to patients with breast cancer can be reduced by up to 80% without causing a rise in the rate of locoregional recurrences.

Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta.

Betacellulin is a member of the epidermal growth factor (EGF) family. These soluble proteins are ligands for one or more of the four receptor tyrosine kinases encoded by the erbB gene family (erbB-1/epidermal growth factor receptor (EGFR), neu/erbB-2/HER2, erbB-3/HER3 and erbB-4/HER4). While evidence suggests that betacellulin is a ligand for the EGFR, the ability of betacellulin to regulate other erbB family receptors has not been analysed. Previously we engineered derivatives of the mouse Ba/F3 hematopoietic cell line to ectopically express erbB family receptors, singly and in pairwise combinations. We have stimulated this panel of cell lines with betacellulin and two other EGF family members, EGF itself and neuregulin-beta (NRG-beta). In the cell lines expressing a single erbB family receptor, betacellulin not only stimulated EGFR tyrosine phosphorylation, but it activated erbB-4 as well. Furthermore, in the double recombinant Ba/F3 derivatives, betacellulin stimulated a complex pattern of receptor phosphorylation distinct from the patterns activated by NRG-beta and EGF. Moreover, betacellulin stimulated a complex pattern of interleukin-3 independence in the Ba/F3 derivatives distinct from those activated by NRG-beta and EGF. These data identify a novel receptor for betacellulin and establish that different EGF family ligands activate distinct patterns of receptor phosphorylation and coupling to cellular signaling pathways.

The cellular response to neuregulins is governed by complex interactions of the erbB receptor family.

Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross talk. We have expressed the four human erbB family receptors, singly and in pairwise combinations, in a pro-B-lymphocyte cell line (Ba/F3) and investigated the range of interactions activated by the epidermal growth factor homology domain of the agonist neuregulin beta. The results provide the first comprehensive analysis of the response of this receptor family to a single peptide agonist. This peptide induced complex patterns of receptor tyrosine phosphorylation and regulation of Ba/F3 cell survival and proliferation. These data demonstrate the existence of several previously undocumented receptor interactions driven by neuregulin.