Minichromosome maintenance protein 3 elicits a cancer-restricted immune response in patients with brain malignancies and is a strong independent predictor of survival in patients with anaplastic astrocytoma.

PURPOSE: The identification of new molecular markers in astrocytic tumors may help to understand the biology of these tumors in more detail. Informative tumor markers may represent prognostic factors for response to therapy and outcome as well as potential targets for novel anticancer therapies. EXPERIMENTAL DESIGN: Tumor-associated antigens were identified by immunoscreening of a human glioma cDNA expression library with allogeneic sera from patients with diffuse astrocytoma (WHO grades 2-4). The expression of one of the identified antigens, the replication licensing factor minichromosome maintenance protein 3 (MCM3), was analyzed by immunohistochemistry in 142 primary and 27 recurrent astrocytomas (WHO grades 2-4). In addition, 98 serum specimens from patients with primary and secondary brain malignancies and 30 serum specimens from healthy controls were examined by serologic immunoscreening for immunoreactivity with MCM3. RESULTS: MCM3 is overexpressed in human astrocytic tumors and elicits a cancer-restricted humoral immune response in 9.3% (9 of 97) of patients with brain tumors (n = 95) and brain metastases (n = 2) but not in healthy controls. Expression of MCM3 in diffuse astrocytoma is significantly associated with age (P < 0.001), histologic grade (P < 0.001), time to recurrence (P = 0.01), and expression of the proliferation marker Ki-67 (P < 0.001) but not with sex (P = 0.800). Univariate and multivariate Cox regression analysis confirmed MCM3 expression as an independent predictor of poor outcome in astrocytoma patients (P < 0.001 for both). CONCLUSIONS: MCM3 may represent a glioma-associated antigen with significant prognostic role as well as have some potential as a target for cancer-directed therapy.     

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.     

The timing of drain removal—empiricism or science?

Surgical drains are commonly used in plastic surgery. Drains are subsequently removed at arbitrary volumes depending on local protocols. The rational for when to remove a drain has not been scientifically determined. We compared removal of drains at ≤30?ml/24?h vs. ≤50?ml/24?h for 158 wounds, in 90 patients. Postoperative complications, length of hospital stay and resulting cost–benefit were considered. Prospective data were collected for two consecutive similar cohorts of patients undergoing abdominoplasty, bilateral breast reduction and breast augmentation. In the first cohort, drains were removed when drainage was ≤30?ml/24?h and the second cohort when ≤50?ml/24?h. Demographics, days of drainage, surgeon grade and duration of postoperative hospital stay were recorded. Patient records were then analysed and complications recorded, including haematoma, infection, seroma, wound breakdown and fat necrosis. The median postoperative stay for all three operations for both drainage cohorts was similar with no statistically significant difference; however, the drainage time in breast augmentation was significantly less in the <50?ml/24?h group. There were no significant differences in outcome measures between the patients undergoing abdominoplasty, breast reduction or breast augmentation. Drain removal at ≤50 vs. ≤30?ml/24?h did not result in an increase in postoperative morbidity or adverse outcome in any of the three different operation types.     

A retrospective, pooled data analysis of the safety of pegaptanib sodium in the treatment of age-related macular degeneration in subjects with or without diabetes mellitus

ABSTRACT: BACKGROUND: To evaluate the safety of pegaptanib sodium 0.3 mg intravitreal injection in the treatment of neovascular age-related macular degeneration in subjects with or without diabetes mellitus. METHODS: A pooled, retrospective, analysis was conducted of data from 9 sponsor-administered, randomized, open-label trials. Subjects who received pegaptanib by randomization or change in dose assignment, crossover design, or protocol amendment, were included. Reports of endophthalmitis, increased intraocular pressure, retinal injury, intraocular hemorrhage, traumatic cataract, hypersensitivity reactions, stroke, myocardial infarction, and other arterial thromboembolic events defined by the Antiplatelet Trialists' Collaboration were identified by Medical Dictionary for Regulatory Activities preferred terms. Adverse events were summarized from the first injection to 42 days after the last injection. The incidence of adverse events was stratified by the presence/absence of diabetes. RESULTS: Of 1,586 subjects enrolled, 165 (10.4%) had a history of diabetes mellitus and 1,421 (89.6%) did not. The 2 populations were similar at baseline. Based on the comparison of prespecified ocular, hypersensitivity, and Antiplatelet Trialists' Collaboration event terms, the safety review did not identify any notable differences between the 2 populations. CONCLUSIONS: This retrospective analysis found no increased safety risk resulting from treatment with pegaptanib 0.3 mg in individuals with neovascular age-related macular degeneration and concomitant diabetes mellitus.