Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Ingroup perception and responses to stigma among persons with mental illness.

OBJECTIVE: Mental illness stigma is common, but it is unclear why it affects some individuals more than others. We tested the hypothesis that the way persons with mental illness perceive their ingroup (people with mental illness) in terms of group value, group identification and entitativity (perception of the ingroup as a coherent unit) shapes their reaction to stigma. METHOD: Ingroup perceptions, perceived legitimacy of discrimination and reactions to stigma (educating or helping others, social performance, secrecy, social distance, hopelessness) were assessed among 85 people with mental illness using questionnaires and a standardized role-play test. RESULTS: Controlling for depression and perceived discrimination, high group value and low perceived legitimacy of discrimination predicted positive reactions to stigma. High group identification and entitativity predicted positive reactions only in the context of high group value or low perceived legitimacy of discrimination. CONCLUSION: Group value and perceived legitimacy of discrimination may be useful targets to help people with mental illness to better cope with stigma.

Standard preoperative analgesia with or without fascia iliaca compartment block for femoral neck fractures.

PURPOSE: To compare the visual analogue score (VAS) for pain in patients with femoral neck fracture who received standard preoperative analgesia with or without fascia iliaca compartment block (FICB). METHODS: In patients with femoral neck fracture, 69 patients who received standard preoperative analgesia (regular paracetamol 1g 4 times a day, codeine 60 mg 4 times a day, and opioid 10 mg 2 hourly as required) were compared with 50 patients who received standard preoperative analgesia plus FICB. VAS for pain at rest and on movement (hip flexion) was assessed before FICB and 15 minutes, 2 and 8 hours after FICB. The amount of additional opioid required and the incidence of opioid overdose (necessitating administration of naloxone) were determined. RESULTS: VAS for pain was significantly lower after standard analgesia plus FICB than standard analgesia alone (p=0.001). The analgesic effect (pre-score minus post-score) of standard analgesia plus FICB did not differ between genders (p=0.57) or fracture patterns (p=0.79). 19 (38%) patients with standard analgesia plus FICB required no additional opioid analgesia. Compared with standard analgesia alone, addition of FICB reduced the mean dose of opioid from 6.2 to 2.0 (p=0.001) and the number of opioid overdose from 7.2% to 0% (p=0.001). No patient had any complication following FICB. CONCLUSION: In patients with femoral neck fracture, FICB reduced the need for additional opioid analgesia and avoided the risk of opioid overdose and respiratory depression.

Chronic right-sided myocarditis mimicking arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia (ARVD) is a cause of right ventricular heart failure and has been implicated in some cases of sudden death in young adults. It is well known that a large majority of patients with ARVD have histological evidence suggestive of inflammation. Here we report a unique case of chronic myocarditis limited to the right ventricle and right side of the interventricular septum which presented clinically as ARVD. The fact that right sided myocarditis can clinically mimic the genetic disease of classic arrhythmogenic right ventricular dysplasia has therapeutic implications for the patient and relatives.

Differential expression of RANTES chemokine, TGF-beta, and leukocyte phenotype in acute cellular rejection and quilty B lesions.

BACKGROUND: Because of the complexity of the trabeculated endocardial surface and tangential histologic sectioning, the differentiation of acute cellular rejection (ACR) from Quilty B lesions (QB) in endomyocardial biopsies (EMBs) is problematic. We hypothesized that the phenotype chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) expression of infiltrating cells and the pattern of expression of transforming growth factor-beta (TGF-beta) may distinguish ACR from QB. In previous studies, the number of RANTES-positive cells and the expression of TGF-beta correlated with the severity of rejection. METHODS: We used immunohistochemical techniques to stain sections of human EMBs with only QB (n = 14) or with only ACR (International Society for Heart and Lung Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7) for B (CD20) and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF-beta expression. We graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%, and 4 = 76% to 100%). RESULTS: When ACR was compared with QB, we found no difference in the proportion of myocardial B cells (0.9 +/- 0.3 vs 1.1 +/- 0.3, p = 0.17); however, we found a lesser proportion of T cells (1.8 +/- 0.5 vs. 2.8 +/- 0.9, p <0.01) but more macrophages (2.9 +/- 0.5 vs. 1.1 +/- 0.6, p < 0.0001) in ACR than in QB. We also found more RANTES-positive leukocytes in ACR vs. QB (2.8 +/- 1.3 vs. 1.9 +/- 0.9, p = 0.03). In QB, many endocardial vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injured myocytes in both ACR and QB expressed TGF-beta. CONCLUSIONS: In ACR, although T-lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells are T-lymphocytes and less that 50% of leukocytes will express RANTES. B cells are present in both ACR and QB, but on average comprise only 25% of the cells present. Thus, a relatively simple immunohistochemical analysis of endomyocardial biopsies may be useful in distinguishing ACR from QB.

Gordonia bronchialis sternal wound infection in 3 patients following open heart surgery: intraoperative transmission from a healthcare worker.

We describe an investigation of 3 postoperative Gordonia bronchialis sternal infections. A nurse anesthetist was identified as the source of the outbreak, her scrubs likely becoming contaminated by her home washing machine. The outbreak ended after disposal of the implicated washing machine. Domestic laundering of surgical scrubs may need reevaluation.

Quality and productivity assessment of clinical pharmacy interventions.

The goal of our program was to implement an easily maintained system that could document, classify, and determine the economic significance of clinical pharmacy interventions on a medicine division of an 874-bed university teaching hospital. This clinical intervention documentation system, which emphasizing both quality of care issues and pharmacist productivity, can be easily implemented by other institutions.