Recombinant factor VIIa is effective at reversing coagulopathy in a lactic acidosis model.

BACKGROUND: The interplay of coagulopathy, acidosis, and hypothermia contributes to the death of the most seriously injured trauma patients. Because of in vitro testing and retrospective series, current recommendations advise correcting acidosis before administering recombinant factor VII (rFVIIa). METHODS: A lactic acidosis was induced in 40 kg swine, and 10 blood samples were withdrawn for testing. rFVIIa was added to the samples with and without bicarbonate correction of the pH. Conventional coagulation assays as well as rotational thromboelastography (ROTEM) were performed on these in vitro samples. Additionally, 10 acidotic and coagulopathic animals had rFVIIa administered after randomization to pH correction with bicarbonate, or remaining acidotic. Conventional coagulation and ROTEM assays were performed on the animals. RESULTS: Ex-vivo samples had a mean pH of 7.14 and International Normalized Ratio (INR) of 1.46. Addition of rFVIIa to these samples corrected the INR to 0.98 (p < 0.05). A similar effect was seen for the ROTEM extem Clotting Time (extem CT). Bicarbonate correction alone of these samples had only a modest effect on INR (1.36, p < 0.05). When administered in vivo to acidotic animals (pH, 7.15), rFVIIa lowered the INR from 1.49 to 1.01 (p < 0.05). Similar improvements in extem CT were seen. CONCLUSIONS: rFVIIa is effective at reversing the coagulopathy from lactic acidosis in a large animal model. Recommendations against its use in acidotic patients may not be valid.

Transcriptional analysis of novel hormone receptors PGRMC1 and PGRMC2 as potential biomarkers of breast adenocarcinoma staging.

BACKGROUND: The expression of progesterone receptor membrane component 1 (PGRMC1) in breast cancer has generated interest in this recently discovered protein because of its role in tumorigenesis. However, correlations between patient age, PGRMC1 gene expression, breast cancer morphology, and breast cancer stage have not been adequately studied. Furthermore, very little is known about possible roles for other PGRMC isoforms in breast cancer, like PGRMC2. Thus, we examined the expression of PGRMC1 and PGRMC2 mRNA by relative quantitative PCR (RelqPCR) and determined whether transcript levels correlate with age, breast cancer staging, estrogen receptor alpha (ERα) status, and other morphometric features routinely used during the pathological examination of breast ductal adenocarcinomas. METHODS: Twenty-eight frozen or paraffin embedded breast cancer samples (ductal carcinoma in situ and stages I thru IV invasive ductal adenocarcinoma) and 10 control benign breast tissue samples were randomly selected and interrogated by RelqPCR to determine PGRMC1, 2, and ERα mRNA transcript levels. To control for slight variations in sample preparation, receptor transcript was normalized to the housekeeping gene phosphoglycerate kinase 1 (PGK1). Descriptive statistics and ANOVA of multiparametric datasets were used to correlate transcript levels with pathological staging parameters. RESULTS: PGRMC1 mRNA levels decreased significantly with patient age (Pearson's correlation -0.369; P=0.035), whereas PGRMC2 levels did not. Although the mean relative expression of PGRMC1 significantly decreased in stage II breast cancer compared with controls (P=0.050), it was no longer significant when age was considered a covariance (P=0.371). On the other hand, PGRMC2 mRNA transcript was significantly decreased in stage II breast cancer when compared to stage III cancer (P=0.028) in a manner independent of age (corrected model Bonferroni pair wise comparison, P=0.036). Furthermore, PGRMC2 levels positively correlated with ERα mRNA transcripts in patients with ER positive tumors (Pearson's correlation 0.503, P=0.096). CONCLUSIONS: Decreases in PGRMC1 mRNA are partially explained by increasing patient age. On the other hand, compared to stage III, PCRMC2 mRNA was significantly decreased in stage II adenocarcinoma of the breast in an age-independent manner. Additionally, PGRMC2 mRNA levels displayed a positive correlation with ERα transcripts. Thus, in addition to morphometric pathologic staging criteria, measurements of PGRMC2 mRNA may be useful for distinguishing low stage tumors from higher stages that require more aggressive clinical management, and may be a useful test when tumor ER IHC results are equivocal.

Primary closure of stoma site wounds after ostomy takedown.

BACKGROUND: Ostomy reversal is considered a contaminated surgery and, thus, primary closure is believed to increase infection. Various closure techniques have been described and postulated to be superior to primary closure in regards to decreasing stoma site wound infections. The literature has varied in its support for this hypothesis. METHODS: A retrospective review was performed evaluating several variables including stomal closure method, patient demographics, steroid/immunosuppressant use, chemotherapy or radiation, perioperative antibiotics, and surgical indication to determine whether there was any association with the development of wound infections. RESULTS: Of 75 patients undergoing ostomy reversal, delayed primary closure/packing/secondary intention was used in 49 (65%), and 26 underwent primary closure (35%). Four patients (5.3%) developed stoma site infections; all had delayed primary closure or packing of their wound (P = .39). No variable was associated significantly with an increased risk of stoma site wound infections. CONCLUSIONS: Primary closure does not increase the rate of infection.