The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis.

BACKGROUND: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our working hypothesis was that, with the application of digital image analysis technology, visually unquantifiable breast cancer microarchitectural features can be rigorously assessed and tested as prognostic parameters for invasive breast carcinoma of no special type. METHODS: Digital image analysis was performed using public domain software (ImageJ) on tissue microarrays from a cohort of 696 patients, and validated with a commercial platform (Visiopharm). Quantified features included elements defining tumour microarchitecture, with emphasis on the extent of tumour-stroma interface. The differential prognostic impact of tumour nest microarchitecture in the four immunohistochemical surrogates for molecular classification was analysed. Prognostic parameters included axillary lymph node status, breast cancer-specific survival, and time to distant metastasis. Associations of each feature with prognostic parameters were assessed using logistic regression and Cox proportional models adjusting for age at diagnosis, grade, and tumour size. RESULTS: An arrangement in numerous small nests was associated with axillary lymph node involvement. The association was stronger in luminal tumours (odds ratio (OR) = 1.39, p = 0.003 for a 1-SD increase in nest number, OR = 0.75, p = 0.006 for mean nest area). Nest number was also associated with survival (hazard ratio (HR) = 1.15, p = 0.027), but total nest perimeter was the parameter most significantly associated with survival in luminal tumours (HR = 1.26, p = 0.005). In the relatively small cohort of triple-negative tumours, mean circularity showed association with time to distant metastasis (HR = 1.71, p = 0.027) and survival (HR = 1.8, p = 0.02). CONCLUSIONS: We propose that tumour arrangement in few large nests indicates a decreased metastatic potential. By contrast, organisation in numerous small nests provides the tumour with increased metastatic potential to regional lymph nodes. An outstretched pattern in small nests bestows tumours with a tendency for decreased breast cancer-specific survival. Although further validation studies are required before the argument for routine quantification of microarchitectural features is established, our approach is consistent with the demand for cost-effective methods for triaging breast cancer patients that are more likely to benefit from chemotherapy.

An uncemented metal-backed glenoid component in total shoulder arthroplasty for osteoarthritis: factors affecting survival and outcome.

BACKGROUND: The reported survivorship of total shoulder replacement (TSR) is variable. This is probably related to implant design. We report the outcome and survivorship of the uncemented glenoid in patients with osteoarthritis receiving a TSR with an intact or repairable rotator cuff at surgery. METHODS: Thirty-two consecutive patients were analysed after TSR using a screw-fixed porous coated metal-back glenoid performed by a single surgeon, with a minimum follow-up of five years. Thirty-three TSRs in 32 patients (19 women) with a mean age of 67 years were analysed, two of whom died before five years of follow-up. Thirty patients (31 shoulders) were monitored for a mean of 95 months (60-173 months). RESULTS: The Constant score improved by 22 points (p < 0.001). The only significant predictor of outcome on logistic regression analysis was the preoperative Constant score, with better scores resulting in a lesser improvement at last follow-up (p < 0.0001). Implant survivorship at ten years was 93 %. Three were revisions: two for polyethylene wear (both at six years) but with a well-fixed glenoid, and another for loosening of the glenoid at 11 years postoperatively. Univariate analysis identified that younger age (56 year vs. 68 years, p = 0.03) and a higher combined preoperative Constant score (35.7 vs. 21.5, p = 0.03) were both predictors of failure. CONCLUSION: The uncemented glenoid performs well in the medium term for osteoarthritis of the shoulder in older patients, giving improved and sustained functional outcome. Age and preoperative level of function are predictors of outcome and survival.

Properties of cold agglutinin and group carbohydrate-specific antibodies isolated from group C streptococcal antisera.

The relationship between erythrocyte autoreactive cold agglutinin (CA) antibodies and group carbohydrate-specific antibodies in hyperimmune rabbit Group C streptococcal antisera was investigated. The different antibody preparations examined were isolated from autologous erythrocyte, Group C carbohydrate, and alpha-GalNAc immunoabsorbents. Each population was subsequently tested for SRBC reactivity, RRBC autoreactivity, and carbohydrate and ligand reactivity, in hemagglutination assay, direct biphasic hemolytic and hemolytic inhibition assays, and radioimmunoassay. In absorption experiments, CA antibodies present in unfractionated serum and represented as purified IgG and IgM preparations, were reactive with Group C carbohydrate, but poorly reactive with alpha-GalNAc immunoabsorbent. In addition, CA antibody activity present in carbohydrate-eluted material, was absent in alpha-GalNAc-eluted material as determined by hemagglutination and direct hemolytic assay. By radioimmunoassay, carbohydrate-eluted and alpha-GalNAc-eluted streptococcal antibodies, and alpha-GalNAc-eluted BSA-alpha-GalNAc antibodies, exhibited similar reactivity with 125I-BSA-alpha-GalNAc antigen, and with GalNAc in radioimmunoassay inhibition experiments. In contrast to these results, both IgG and IgM CA antibodies exhibited a relatively low avidity toward 125I-BSA-alpha-GalNAc. Yet relative to the other antibody populations tested in radioimmunoassay inhibition experiments, CA antibodies did not exhibit a particularly significant difference in reactivity with GalNAc. However, recognition of other Gal-containing ligands, e.g. Mel and Lac, was restricted to the CA antibody preparations. These data suggest that CA antibodies present in Group C streptococcal antisera do not represent a higher affinity cross-reactive anticarbohydrate population, but instead perhaps represent cross-reactive carbohydrate-specific antibodies produced in response to nonimmunodominant Group C carbohydrate determinants.

Hospital security: is the patient at risk?

This article focuses on the safety and security of the hospital patient, especially the role of the caregiver, as an important element in today's hospital environment. The author believes that not only the nursing unit but the entire hospital employee staff must be utilized to provide a reasonably safe and secure environment for not only the patient, but the staff and visitors as well.

Security as a management service.

Noting that hospital security must be viewed as an element of management that supports professional patient care, the author presents a comprehensive overview of the various healthcare security functions from a service-oriented, management perspective.

Hospital security: "a current look".

The results of a hospital security survey using a random sampling of hospital organizations in the AHA Membership Directory. The survey covered staffing, security attire and equipment, training, use of physical security, and bicycle patrols. No serious security staffing cutbacks have taken place in the past two years, according to survey respondents.

Assessment of shoulder function using the coronal plane angle.

BACKGROUND: Assessment of shoulder function is an essential part of clinical practice. Current scoring relies on multiple subjective and / or objective components. We present a single angular measurement, the coronal plane angle, which relates to the functional assessment of the shoulder. MATERIALS AND METHODS: One hundred patients were prospectively enrolled and assessed using the Constant-Murley score and the Oxford shoulder questionnaire, and the coronal plane angle was measured for both symptomatic and asymptomatic shoulder. RESULTS: NINE PATIENTS WERE EXCLUDED FROM THE STUDY: Four had apprehension and five were not able to get their hand to head. The mean coronal plane angle on the symptomatic side was +11.3 degrees and the asymptomatic side -1.5 degrees (P

Reactivity with rabbit immunoglobulin G of cold agglutinins isolated from group C streptococcal antisera.

Cold agglutinin antibodies were isolated from group C streptococcal antisera by thermal elution from rabbit erythrocytes. These antibodies reacted with bovine submaxillary mucin, fetuin, immunoglobulin G, and the Fc fragment of immunoglobulin G in hemolytic inhibition assays. Further, in radioimmunoassay these antibodies reacted with the major glycopeptide fragment of rabbit immunoglobulin G. Affinity-purified group carbohydrate-specific antibodies reacted weakly with glycopeptide. These data suggest that certain populations of antibody in group C streptococcal antisera may participate in tissue reactivity via interaction with cell surface glycoproteins, including immunoglobulin G.

Association of bacterial carbohydrate-specific cold agglutinin antibody production with immunization by group C, group B type III, and Streptococcus pneumoniae type XIV streptococcal vaccines.

Rabbits immunized with group B type III, group C, and Streptococcus pneumoniae type XIV streptococcal vaccines developed autoantibodies reactive with autologous and isologous erythrocytes and human O-positive erythrocytes at reduced temperatures. The cold agglutinin antibodies were present in both the immunoglobulin M (IgM) and IgG fractions of group C streptococcal antiserum and in the IgM fraction of group B type III and S. pneumoniae type XIV antisera. BALB/c, CF1, and local strains of mice immunized with group B type III and S. pneumoniae type XIV streptococcal vaccines also produced a cold agglutinin antibody reactive with rabbit and human erythrocytes. The cold agglutinin antibodies were reactive with saccharide compounds representative of the determinants present on the individual bacterial carbohydrate structures, individual vaccine preparations, and isolated polysaccharides. The group C antibodies in rabbits were reactive with sugar ligands in the following order: N-acetylgalactosamine greater than melibiose greater than lactose greater than galactose greater than glucose. Group B type III and S. pneumoniae type XIV cold agglutinin antibodies in rabbit antisera, however, displayed reactivities different from group C antibodies and from each other. Group B type III antibodies reacted with galactose greater than lactose greater than N-acetylgalactosamine greater than glucose greater than rhamnose; S. pneumoniae type XIV antibodies reacted with lactose greater than melibiose greater than galactose greater than glucose greater than N-acetylgalactosamine. The same relative ligand specificity was observed for the cold agglutinin antibodies in S. pneumoniae type XIV mouse antisera. The cold agglutinin antibodies in group B type III and S. pneumoniae type XIV antiserum reacted with erythrocytes at higher temperatures (up to 31 degrees C) than did group C antibodies (up to 14 degrees C). In addition, S. pneumoniae type XIV antibodies did not discriminate between I- or i-bearing human erythrocytes to a significant extent. The results obtained provide substantial evidence that autoreactive cold agglutinin antibodies produced by immunization with these vaccines represent subpopulations of bacterial carbohydrate-specific antibodies that cross-react with mammalian carbohydrate structures.