31 research outputs found

    The multiplex bead array approach to identifying serum biomarkers associated with breast cancer

    Get PDF
    Introduction Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Methods Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex (TM) bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Results Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity. Conclusions The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. Further validation is required before array-based technology is used routinely for early detection of breast cancer.Kenny HA, 2008, J CLIN INVEST, V118, P1367, DOI 10.1172/JCI33775Shah FD, 2008, INTEGR CANCER THER, V7, P33, DOI 10.1177/1534735407313883Carlsson A, 2008, EUR J CANCER, V44, P472, DOI 10.1016/j.ejca.2007.11.025Nolen BM, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr2096Brogren H, 2008, THROMB RES, V122, P271, DOI 10.1016/j.thromres.2008.04.008Varki A, 2007, BLOOD, V110, P1723, DOI 10.1182/blood-2006-10-053736Madsen CD, 2007, J CELL BIOL, V177, P927, DOI 10.1083/jcb.200612058Levenson VV, 2007, BBA-GEN SUBJECTS, V1770, P847, DOI 10.1016/j.bbagen.2007.01.017VAZQUEZMARTIN A, 2007, EUR J CANCER, V43, P1117GARCIA M, 2007, GLOBAL CANC FACTS FIMoore LE, 2006, CANCER EPIDEM BIOMAR, V15, P1641, DOI 10.1158/1055-9965.EPI-05-0980Borrebaeck CAK, 2006, EXPERT OPIN BIOL TH, V6, P833, DOI 10.1517/14712598.6.8.833Zannis VI, 2006, J MOL MED-JMM, V84, P276, DOI 10.1007/s00109-005-0030-4Jemal A, 2006, CA-CANCER J CLIN, V56, P106Silva HC, 2006, NEOPLASMA, V53, P538Chahed K, 2005, INT J ONCOL, V27, P1425Jain KK, 2005, EXPERT OPIN PHARMACO, V6, P1463, DOI 10.1517/14656566.6.9.1463Abe O, 2005, LANCET, V365, P1687Paradis V, 2005, HEPATOLOGY, V41, P40, DOI 10.1002/hep.20505Molina R, 2005, TUMOR BIOL, V26, P281, DOI 10.1159/000089260Furberg AS, 2005, CANCER EPIDEM BIOMAR, V14, P33Benoy IH, 2004, CLIN CANCER RES, V10, P7157Song JS, 2004, BLOOD, V104, P2065, DOI 10.1182/blood-2004-02-0449Schairer C, 2004, J NATL CANCER I, V96, P1311, DOI 10.1093/jnci/djh253Hellman K, 2004, BRIT J CANCER, V91, P319, DOI 10.1038/sj.bjc.6601944Roselli M, 2004, CLIN CANCER RES, V10, P610Zhou AW, 2003, NAT STRUCT BIOL, V10, P541, DOI 10.1038/nsb943Hapke S, 2003, BIOL CHEM, V384, P1073Miller JC, 2003, PROTEOMICS, V3, P56Amirkhosravi A, 2002, BLOOD COAGUL FIBRIN, V13, P505Bonello N, 2002, HUM REPROD, V17, P2272Li JN, 2002, CLIN CHEM, V48, P1296Louhimo J, 2002, ANTICANCER RES, V22, P1759Knezevic V, 2001, PROTEOMICS, V1, P1271Di Micco P, 2001, DIGEST LIVER DIS, V33, P546Ferrigno D, 2001, EUR RESPIR J, V17, P667Webb DJ, 2001, J CELL BIOL, V152, P741Gion M, 2001, EUR J CANCER, V37, P355Schonbeck U, 2001, CELL MOL LIFE SCI, V58, P4Blackwell K, 2000, J CLIN ONCOL, V18, P600Carriero MV, 1999, CANCER RES, V59, P5307Antman K, 1999, JAMA-J AM MED ASSOC, V281, P1470Loskutoff DJ, 1999, APMIS, V107, P54Molina R, 1998, BREAST CANCER RES TR, V51, P109Bajou K, 1998, NAT MED, V4, P923Chan DW, 1997, J CLIN ONCOL, V15, P2322Chu KC, 1996, J NATL CANCER I, V88, P1571vanDalen A, 1996, ANTICANCER RES, V16, P2345Yamamoto N, 1996, CANCER RES, V56, P2827KOCH AE, 1995, NATURE, V376, P517HADDAD JG, 1995, J STEROID BIOCHEM, V53, P579FOEKENS JA, 1994, J CLIN ONCOL, V12, P1648GEARING AJH, 1993, IMMUNOL TODAY, V14, P506HUTCHENS TW, 1993, RAPID COMMUN MASS SP, V7, P576DECLERCK PJ, 1992, J BIOL CHEM, V267, P11693GABRIJELCIC D, 1992, AGENTS ACTIONS S, V38, P350BIEGLMAYER C, 1991, TUMOR BIOL, V12, P138DNISTRIAN AM, 1991, TUMOR BIOL, V12, P82VANDALEN A, 1990, TUMOR BIOL, V11, P189KARAS M, 1988, ANAL CHEM, V60, P2299, DOI 10.1021/ac00171a028LERNER WA, 1983, INT J CANCER, V31, P463WESTGARD JO, 1981, CLIN CHEM, V27, P493TROUSSEAU A, 1865, CLIN MED HOTEL DIEU, V3, P654*R PROJ, R PROJ STAT COMP1

    The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

    Get PDF
    Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

    Clinical and echocardiographic follow-up of patients following surgical heart valve repair or replacement: a tertiary centre experience

    No full text
    International best practice guidelines recommend lifelong follow-up of patients that have undergone valve repair or replacement surgery and provide recommendations on the utilization of echocardiography during follow-up. However, such follow-up regimes can vary significantly between different centres and sometimes within the same centre. We undertook this study to determine the patterns of clinical follow-up and use of transthoracic echocardiography (TTE) amongst cardiologists in a large UK tertiary centre. In this retrospective study, we identified patients that underwent heart valve repair or replacement surgery in 2008. We used local postal codes to identify patients within our hospital’s follow-up catchment area. We determined the frequency of clinical follow-up and use of transthoracic echocardiography (TTE) during the 9-year follow-up period (2009–2016 inclusive). Of 552 patients that underwent heart valve surgery, 93 (17%) were eligible for local follow-up. Of these, the majority (61/93, 66%) were discharged after their 6-week post-operative check-up with no further follow-up. Of the remaining 32 patients, there was remarkable heterogeneity in follow-up regimes and use of TTE. This variation did not correlate with the prosthesis type. In summary, the frequency of clinical follow-up and use of echocardiography is highly variable in contemporary practice. Many patients are inappropriately discharged back to their family doctor with no plans for hospital follow-up. These data further support the creation of dedicated specialist heart valve clinics to optimize patient care, ensure rational use of TTE and optimize adherence with best practice guidelines

    Use of the CHA2DS2VASc score to reduce utilisation of transoesophageal echocardiography prior to ablation for atrial fibrillation

    No full text
    Transoesophageal echocardiography (TOE) is frequently performed prior to atrial fibrillation (AF) ablation to exclude left atrial appendage (LAA) thrombus. However, patients undergoing AF ablation are usually anticoagulated, thus making the presence of thrombus unlikely in most cases. This study aimed to determine whether the CHA2DS2VASc scoring system can be used to identify patients that do not require TOE prior to AF ablation. In this single-centre retrospective study, local institutional and primary care databases and electronic patient records were searched to identify patients that had undergone TOE prior to AF ablation. Patient demographics, CHA2DS2VASc score, TOE findings and anticoagulation status were collected for analysis. Over a 7-year period (2008–2014), 332 patients (age 57 ± 10 years; 74% male) underwent TOE prior to proposed AF ablation. CHA2DS2VASc scores of 0, 1, 2 and >2 were found in 39, 34, 15 and 12% of patients, respectively. The prevalence of LAA thrombus was 0.6% (2 patients) and these 2 patients had risk scores of 2 and 4. No patients with a score of 0 or 1 had LAA thrombus. Patients that are classed as low risk by the CHA2DS2VASc score do not require a pre-ablation TOE to screen for LAA thrombus provided they are adequately anticoagulated. This would lead to a significant reduction in health care expenditures by reducing unnecessary TOE requests and thereby improve patient experience
    corecore