Traumatic labral avulsion from the stable rim: a constant pathology in displaced transverse acetabular fractures

Introduction: During the treatment of a malunited transverse acetabular fracture, a hitherto undescribed extended avulsion of the labrum from the stable acetabular fragment was found. Based on the labral pathomorphology present in this case, the hypothesis was put forward that traumatic acetabular labral avulsions are a constant phenomenon in transverse acetabular fractures. Patients and methods: Fourteen patients underwent capsulotomy and/or surgical dislocation of the involved hip to facilitate open reduction and internal fixation of transverse acetabular fractures. Results: In all cases, the labrum was partially or completely detached from the superior acetabular rim. In eight cases with bucket-handle tears of the labrum from the stable superior fragment, the injured portion was resected back to normal margins. In one case the labrum was avulsed with an attached piece of bone and was repaired by screw fixation. Small separations of the labrum from the underlying acetabular rim occurred at the level of the fractures in five cases with minor displacement and received no treatment. Conclusion: With displaced transverse acetabular fractures, consideration should be given to opening the joint at the time of open reduction and internal fixation to look for associated intracapsular injuries. An avulsed portion of the labrum should be left if stable and undamaged. If unstable and damaged, it is probably better resected and if unstable but intact and/or attached to a bony fragment, it should be repaire

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

MR Evaluation of Radiation Synovectomy of the Knee by Means of Intra-articular Injection of Holmium-166-Chitosan Complex in Patients with Rheumatoid Arthritis: Results at 4-month Follow-up

Objective To determine whether MRI is able to demonstrate the effect of radiation synovectomy after the intra-articular injection of holmium-166-chitosan complex for the treatment of rheumatoid arthritis of the knee. Materials and Methods Fourteen patients aged 36-59 years were treated with 10-20 mCi of holmium-166-chitosan complex. A criterion for inclusion in this study was the absence of observable improvement after 3- or more months of treatment of the knee with disease-modifying anti-rheumatic drugs. MR images were acquired both prior to and 4-months after treatment. Clinical evaluation included the use of visual analog scales to assess pain, and the circumference of the knee and its range of motion were also determined. MR evaluation included measurement of the volume of synovial enhancement and wall thickness, the amount of joint effusion, and quantifiable scoring of bone erosion, bone edema and lymph nodes. Results Visual analog scale readings decreased significantly after radiation synovectomy (p <0.05). MRI showed that joint effusion decreased significantly (p <0.05), and that the volume of synovial enhancement tended to decrease, but to an insignificant extent (p = 0.107). Conclusion The decreased joint effusion noted at 4-month follow-up resulted from radiation synovectomy of the rheumatoid knee by means of intra-articular injection of holmium-166-chitosan complex.ope

Consensus statement: Expedition Inspiration 2004 Breast Cancer Symposium ‘Breast Cancer – the Development and Validation of New Therapeutics’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44225/1/10549_2004_Article_1288.pd

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Psychotherapy for suicidal patients with borderline personality disorder: an expert consensus review of common factors across five therapies

The objective was to review established literature on approaches to the psychotherapy of borderline personality disorder with specfic reference to suicide in order to determine if there were common factors across these efforts that would guide future teaching, practice and research. The publications from the proponents of five therapies for the treatment of suicidal behavior in individuals with borderline personality disorder (BPD), were reviewed and discussed by the members of the Group for the Advanced of Psychiatry, Psychotherapy Committee (GAPPC). Twenty nine published research and summary reports were reviewed of the specific treatments noted above along with two other reviews of common factors for this group of treatments. We used expert consensus as to the salient articles for review and the appropriate level of abstraction for the common factor definition. We formulated a definition of effectiveness and identified six common factors: 1) negotiation of a specific frame for treatment, 2) recognition and insistence on the patient’s responsibilities within the therapy, 3) provision to the therapist of a conceptual framework for understanding and intervening, 4) use of the therapeutic relationship to engage and address suicide, 5) prioritization of suicide as a topic to be actively addressed whenever it emerges, and 6) provision of support for the therapist in the form of supervision, consultation or peer support. We discuss common factors, their formulation, and implications for development and teaching of psychotherapeutic approaches specific to suicide in patients with borderline personality disorder and note that there should be greater attention in practice and education to these issues

Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria