Current incidence and estimated residual risk of transfusion-transmitted infections in donations made to Canadian Blood Services

BACKGROUND: New testing methods such as nucleic acid amplification testing (NAT) and chemiluminescent serologic assays have been introduced, more precise estimates for infectious window periods are available, and a new method for estimating the residual risk (RR) of transfusion-transmitted infections (TTIs) has been developed. Thus, available RR estimates for Canada need to be updated. STUDY DESIGN AND METHODS: Incidence rates for known TTI markers were determined for all allogeneic whole-blood donations made to Canadian Blood Services between 2001 and 2005; they were derived from NAT conversions or seroconversions of repeat donors with at least two donations in a 3-year period. RR estimates for human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) derived from the classical incidence/window-period model were compared to those obtained by the new method that estimates incidence from NAT-positive, antibody-negative donations (NAT-yield cases) from all donors divided by person-years. RESULTS: With the classical method, the RR of HIV (1 per 7.8 million donations) and HCV (1 per 2.3 million) were low; HBV RR was higher (1 per 153,000). HCV RR was significantly lower when estimated with the new method (1 per 13 million). Eleven HCV NAT-yield cases were predicted by applying the classical method to our seroconversion data but only 2 were observed (p = 0.011). Observed HIV-1 NAT-yield cases (n = 1) matched those predicted (n = 0.7). CONCLUSION: New tests have reduced an already low risk of TTI in Canada. HCV RR estimates by two different methods differed but both were low.     

Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast

Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.     

Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas

Pleomorphic lobular carcinomas (PLC) of the breast display histological features associated with classic invasive lobular carcinoma (ILC), yet they also exhibit more conspicuous nuclear atypia and pleomorphism, and an aggressive clinical behaviour. From a breast cancer progression perspective, it is unclear whether PLC is a variant of ILC or is a high-grade invasive ductal carcinoma (IDC) that has lost E-cadherin. The molecular features of 26 PLC were studied using immunohistochemistry [oestrogen receptor (ER), progesterone receptor (PR), HER2, p53 and E-cadherin], 0.9 Mb resolution, microarray-based comparative genomic hybridization (aCGH), fluorescent (FISH) and chromogenic (CISH) in situ hybridization and loss of heterozygosity. Comparative analysis was performed with aCGH data from PLC with classic ILC (16 cases) and high grade IDC (35 cases). PLCs were frequently ER- and PR-positive, E-cadherin-negative and occasionally HER2- and p53-positive. Recurrent copy number changes identified by aCGH included gains on 1q, 8q, 11q, 12q, 16p and 17q and losses on 8p, 11q, 13q, 16q and Xq. Highly recurrent 1q+ (100% of cases), 16p+ (93%), 11q- (53%) and 16q- (93%) and evidence of the der(1;16)/der(16)t(1;16) rearrangement, as detected by FISH, suggested that PLC had a 'lobular genotype'. Focal amplifications were evident at 8p12-p11, 8q24, 11q13.1-q14.1, 12q14, 17q12 and 20q13. Loss of BRCA2 was detected in 40% of PLC by LOH. Comparative analysis of aCGH data suggested the molecular features of PLC (ER/PR-positive, E-cadherin-negative, 1q+, 11q(-), 16p+ and 16q(-)) were more closely related to those of ILC than IDC, implicating an overlapping developmental pathway for these lobular tumour types. Molecular alterations found in PLC that are more typical of high-grade IDC than ILC (p53 and HER2 positivity, 8q+, 17q24-q25+, 13q(-) and amplification of 8q24, 12q14, 17q12 and 20q13) are likely to drive the high-grade and more aggressive biology of PLC.     

Efficacy of panitumumab in older patients with metastatic colorectal cancer: a retrospective analysis using the database of the Hellenic Oncology Research Group (HORG)

Background

Although colorectal cancer (CRC) is a disease of the older patients, older patients are under-represented from randomized trials. Herein we conducted a retrospective analysis for the effect of panitumumab in the management of older patients (≥65?years) patients with metastatic CRC (mCRC) in the Hellenic Oncology Research Group's (HORG) database.

Wrist,hand and finger injuries in Australian football: A prospective observational study of emergency department presentations

Objectives

Investigate the characteristics of wrist, hand and finger (WHF) injuries in Australian footballers presenting to EDs and determine if injury profiles differed between females and males, and between children and adults.

Methods

In this prospective observational study that took place during an entire football season, patients attended 1 of 10 EDs in Victoria, Australia with a WHF injury sustained while playing Australian football. Data were extracted from patient medical records by trained researchers. Data included injury type (e.g. fracture), body part (e.g. metacarpal) and mechanism of injury. Males versus females, and children versus adults were compared using chi-squared tests or Fisher's exact tests.

Results

In total, 528 patients had a WHF injury, of which 105 (19.9%) were female and 308 (59.2%) were children. Fractures and sprains were the most common injury types (45.3% and 38.6%, respectively). Fingers were more often injured than wrists or hands (62.5%, 23.5% and 15.0%, respectively). Ball contact was the most common mechanism of injury (38.1% of injuries). Females were more likely than males to (i) have a sprain/strain injury, (ii) injure a finger (rather than wrist or hand) and (iii) injure themselves through ball contact. Children were more likely to injure their wrists, have a sprain/strain injury, or be injured falling to the ground. Adults were more likely to dislocate a joint or injure their hands.

Conclusions

Differences in injury type, location and mechanism between females and males, and children and adults, suggest an opportunity for customised injury prevention and management strategies by sex and age.