Purpose: To identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression
profiling were done on pretreatment biopsies.
Experimental ...Design: Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation.
Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression
profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and
compared to those with residual disease, non-pCR (NR).
Results: Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from
patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher
levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel
sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched
in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based
treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated
with response to therapy at the time of surgery.
Conclusion: We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest
the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers
that associate with response to neoadjuvant taxane–based therapy. Clin Cancer Res; 16(2); 681–90
Atrial fibrillation (AF) is a common diagnosis of patients presenting to the emergency department (ED). Intravenous (IV) diltiazem bolus is often the initial drug of choice for acute management of AF ...with rapid ventricular response (RVR). The route of diltiazem after the initial IV loading dose may influence the disposition of the patient from the ED. However, no studies exist comparing oral (PO) immediate release and IV continuous infusion diltiazem in the emergency setting. The objective of this study was to compare the incidence of treatment failure, defined as a heart rate (HR) of >110 beats/min at four hours or conversion to another agent, between PO immediate release and IV continuous infusion diltiazem after an initial IV diltiazem loading dose in patients in AF with RVR.
This was a single-center, observational, retrospective study conducted at a tertiary academic medical center. The study population included patients ≥18 years old who presented to the ED in AF with a HR > 110 beats/min and received an initial IV diltiazem loading dose. We used multivariate logistic regression to assess the association between routes of administration and treatment failure.
A total of 111 patients were included in this study. Twenty-seven percent (11/41) of the patients in the PO immediate-release group had treatment failure compared to 46% (32/70) in the IV continuous-infusion group. The unadjusted odds ratio (OR) of treatment failure with PO was less than IV at 0.4 (95% confidence interval CI 0.18, 0.99, p = 0.046). When we performed a multivariate analysis adjusted for race and initial HR, PO was still less likely to be associated with treatment failure than IV with an OR of 0.4 (95% CI 0.15, 0.94, p = 0.041). The median dose of PO diltiazem and IV continuous infusion diltiazem at four hours was 30 mg and 10 mg/h, respectively.
After a loading dose of IV diltiazem, PO immediate-release diltiazem was associated with a lower rate of treatment failure at four hours than IV continuous infusion in patients with AF with RVR.
We describe one patient with acute Epstein-Barr virus (EBV) infection associated with severe thrombocytopenia and review 36 additional cases reported in the literature. Complications of EBV infection ...due to severe thrombocytopenia occurred in 10 (27.0%) of 37 patients, and 2 (5.4%) of 37 patients died. Although acute EBV infections are generally benign and self-limiting, thrombocytopenia, a potentially serious complication, should not be overlooked.
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