Citations

The aims of this study were to determine the functional impact and financial burden of isolated and recurrent dislocation after total hip arthroplasty (THA). Our secondary goal was to determine whether there was a difference between patients who were treated non-operatively and those who were treated operatively.We retrospectively reviewed 71 patients who had suffered dislocation of a primary THA. Their mean age was 67 years (41 to 92) and the mean follow-up was 3.8 years (2.1 to 8.2).Because patients with recurrent dislocation were three times more likely to undergo operative treatment (p < 0.0001), they ultimately had a significantly higher mean Harris Hip Score (HHS) (p = 0.0001), lower mean Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (p = 0.001) and a higher mean SF-12 score (p < 0.0001) than patients with a single dislocation. Likewise, those who underwent operative treatment had a higher mean HHS (p < 0.0001), lower mean WOMAC score (p < 0.0001) and a higher mean SF-12 score (p < 0.0001) than those who were treated non-operatively.Recurrent dislocation and operative treatment increased costs by 300% (£11 456; p < 0.0001) and 40% (£5217; p < 0.0001), respectively.The operative treatment of recurrent dislocation results in significantly better function than non-operative management. Moreover, the increase in costs for operative treatment is modest compared with that of non-operative measures.Cite this article: Bone Joint J 2015; 97-B:1046–9.

Background Axillary web syndrome (AWS) is a condition that may develop following breast cancer surgery and that presents as a palpable axillary cord of tissue. Objective The purposes of this study were: (1) to determine the clinical characteristics of AWS related to movement, function, pain, and postoperative edema and (2) to define the incidence of and risk factors for AWS within the first 3 months following breast cancer surgery. Design This was a prospective cohort study with a repeated-measures design. Methods Women who underwent breast cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36) were assessed for AWS, shoulder range of motion, function, pain, and postoperative edema (using girth measurements, bioimpedance, and tissue dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used for risk analysis. Results Seventeen women (47.2%) developed AWS, and AWS persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was significantly lower in the AWS group compared with the non-AWS group at 2 and 4 weeks. There were no differences between groups in measurements of function, pain, or edema at any time point. Trunk edema measured by dielectric constant was present in both groups, with an incidence of 55%. Multivariate analysis determined lower body mass index as being significantly associated with AWS (odds ratio=0.86; 95% confidence interval=0.74, 1.00). Limitations Limitations included a short follow-up time and a small sample size. Conclusion Axillary web syndrome is prevalent following breast/axilla surgery for early-stage breast cancer and may persist beyond 12 weeks. The early consequences include movement restriction, but the long-term effects of persistent AWS cords are yet unknown. Low body mass index is considered a risk factor for AWS.

Background— Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. Methods and Results— We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, –4.2 [–4.9, –3.5] mg/dL and –3.5 [–4.2, –2.7] mg/dL at 12 and 24 weeks, respectively, both P <0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P =0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P =0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P =0.36). Conclusions— In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00987415.

AbstractThe many improvements in breast cancer therapy in recent years have so lowered rates of recurrence that it is now difficult or impossible to conduct adequately powered adjuvant clinical trials. Given the many new drugs and potential synergistic combinations, the neoadjuvant approach has been used to test benefit of drug combinations in clinical trials of primary breast cancer. A recent FDA-led meta-analysis showed that pathologic complete response (pCR) predicts disease-free survival (DFS) within patients who have specific breast cancer subtypes. This meta-analysis motivated the FDA's draft guidance for using pCR as a surrogate endpoint in accelerated drug approval. Using pCR as a registration endpoint was challenged at ASCO 2014 Annual Meeting with the presentation of ALTTO, an adjuvant trial in HER2-positive breast cancer that showed a nonsignificant reduction in DFS hazard rate for adding lapatinib, a HER-family tyrosine kinase inhibitor, to trastuzumab and chemotherapy. This conclusion seemed to be inconsistent with the results of NeoALTTO, a neoadjuvant trial that found a statistical improvement in pCR rate for the identical lapatinib-containing regimen. We address differences in the two trials that may account for discordant conclusions. However, we use the FDA meta-analysis to show that there is no discordance at all between the observed pCR difference in NeoALTTO and the observed HR in ALTTO. This underscores the importance of appropriately modeling the two endpoints when designing clinical trials. The I-SPY 2/3 neoadjuvant trials exemplify this approach. Clin Cancer Res; 21(13); 2911–5. ©2015 AACR.

Objective To better characterize the genomics of patients with biochemical recurrence ( BCR ) who have metastatic disease progression in order to improve treatment decisions for prostate cancer. Methods The expression profiles of three clinical outcome groups after radical prostatectomy ( RP ) were compared: those with no evidence of disease ( NED ; n = 108); those with BCR (rise in prostate‐specific antigen [ PSA ] level without metastasis; n = 163); and those with metastasis ( n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow‐up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology. Results Minimal gene expression differences were observed between adjuvant treatment‐naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin‐mediated proteolysis, DNA repair, androgen, G‐protein coupled and NOTCH signal transduction pathways. Conclusion This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision‐making.

Substantial healthcare resources have been devoted to computer navigation and patient-specific instrumentation systems that improve the reproducibility with which neutral mechanical alignment can be achieved following total knee replacement (TKR). This choice of alignment is based on the long-held tenet that the alignment of the limb post-operatively should be within 3° of a neutral mechanical axis. Several recent studies have demonstrated no significant difference in survivorship when comparing well aligned versus malaligned TKRs. Our aim was to review the anatomical alignment of the knee, the historical and contemporary data on a neutral mechanical axis in TKR, and the feasibility of kinematically-aligned TKRs. Review of the literature suggests that a neutral mechanical axis remains the optimal guide to alignment. Cite this article: Bone Joint J 2014;96-B:857–62.

Abstract Motivations: Gleason score is the most prognostic variable in prostate cancer pathology. Patients with high Gleason (8+) are the most likely to experience biochemical recurrence (BCR), clinical progression (CP) and prostate-cancer specific mortality (PCSM), whereas patients with Gleason ≤6 are expected to have excellent long-term outcomes. However, the majority of prostate cancer patients are diagnosed with Gleason score 7, a heterogeneous group in terms of patient outcomes. In the absence of adverse pathological factors (APF, such as preoperative PSA, SM+, ECE and SVI) most Gleason 7 patients will have excellent outcomes. In contrast, Gleason 7 patients with APF are considered at high-risk for recurrence and therefore are candidates for adjuvant therapy. In this study, we have investigated whether a classifier based on differentially expressed genomic features could be used to improve prognostication of Gleason 7 patients, independent of APF. Methods: Two whole-transcriptome (1.4 million feature) oligonucleotide microarray expression datasets from radical prostatectomy specimens were analyzed. The first one (GEO accession: GSE21032) consisted of 125 fresh frozen (FF) samples from the MSKCC Oncogenome Project and the second dataset had 545 formalin-fixed-paraffin- embedded (FFPE) samples from the Mayo Clinic tumor registry. For genomic feature selection, differential expression in the FF dataset between Gleason ≤6 (n=40) and ≥8 (n=15) was assessed with false discovery rate adjusted t-tests (p&lt;0.05). Next, a k-nearest neighbor (KNN) classifier was trained and tuned using the selected features to predict clinical progression (i.e., positive bone or CT scans after BCR) in the FFPE dataset, again using samples with Gleason score ≤6 (n=63) and ≥8 (n=211). The KNN classifier was evaluated on Gleason score 7 (n=209) FFPE samples (not used for training) using multivariable logistic regression. Results: The KNN classifier segregated the Gleason 7 samples into high and low risk CP groups. The KNN odds ratios were 2.9 (p&lt;0.005), 2.1 (p&lt;0.05) and 2.8 (p&lt;0.05) for BCR, CP and PCSM end-points, respectively when comparing high and low risk groups. Multivariable analysis revealed that the KNN classifier was independently prognostic. Conclusions: A KNN classifier developed using differentially expressed genomic features significantly stratified Gleason score 7 patients for several clinically relevant endpoints. Future validation studies will address the utility of this classifier in predicting pathological Gleason score from biopsy specimens, which may be particularly useful for evaluation of biopsy Gleason 6 cases. In these patients, deferring prostatectomy in favour of active surveillance is an appealing treatment option unless the ‘true’ Gleason of the index lesion is in fact a Gleason 7 or higher, where immediate surgery is likely a life-saving procedure. Citation Format: Nicholas Erho, Thomas Sierocinski, Elai Davicioni, Robert B. Jenkins, Mercedeh Gadhessi, Christine Buerki, Ismael A. Vergara, Anamaria Crisan, Zaid Haddad, Benedikt Zimmermann, Anirban Mitra, Timothy J. Triche. Identification of biomarkers for stratification of Gleason score 7 patients using whole-transcriptome expression profiling [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B46.