Psoas:lumbar vertebra index: central sarcopenia independently predicts morbidity in elderly trauma patients.

INTRODUCTION: Central sarcopenia as a surrogate for frailty has recently been studied as a predictor of outcome in elderly medical patients, but less is known about how this metric relates to outcomes after trauma. We hypothesized that psoas:lumbar vertebral index (PLVI), a measure of central sarcopenia, is associated with increased morbidity and mortality in elderly trauma patients. METHODS: A query of our institutional trauma registry from 2005 to 2010 was performed. Data was collected prospectively for the Pennsylvania Trauma Outcomes Study (PTOS). INCLUSION CRITERIA: age >55 years, ISS >15, and ICU LOS >48 h. Using admission CT scans, psoas:vertebral index was computed as the ratio between the mean cross-sectional areas of the psoas muscles and the L4 vertebral body at the level of the L4 pedicles. The 50th percentile of the psoas:L4 vertebral index value was determined, and patients were grouped into high (>0.84) and low (≤0.83) categories based on their relation to the cohort median. Primary endpoints were mortality and morbidity (as a combined endpoint for PTOS-defined complications). Univariate logistic regression was used to test the association between patient factors and mortality. Factors found to be associated with mortality at p < 0.1 were entered into a multivariable model. RESULTS: A total of 180 patients met the study criteria. Median age was 74 years (IQR 63-82), median ISS was 24 (IQR 18-29). Patients were 58 % male and 66 % Caucasian. Mean PLVI was 0.86 (SD 0.25) and was higher in male patients than female patients (0.91 ± 0.26 vs. 0.77 ± 0.21, p < 0.001). PLVI was not associated with mortality in univariate or multivariable modeling. After controlling for comorbidities, ISS, and admission SBP, low PLVI was found to be strongly associated with morbidity (OR 4.91, 95 % CI 2.28-10.60). CONCLUSIONS: Psoas:lumbar vertebral index is independently and negatively associated with posttraumatic morbidity but not mortality in elderly, severely injured trauma patients. PLVI can be calculated quickly and easily and may help identify patients at increased risk of complications.

Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor. METHODS: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone. RESULTS: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders. CONCLUSIONS: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.

The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin.

We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) (respectively, TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha)) to determine the optimal dosage and formulation of aspirin to inhibit TXA2 production while sparing PGI2. In a randomized, parallel study, 52 healthy male volunteers (62 independent observations) with no history of bleeding disorders were given 80 mg or 325 mg of regular aspirin, or 325 mg of enteric-coated aspirin to ingest daily (14 pills) or every other day (7 pills) for a continuous 14 day period. Bleeding times were performed on day 1 before aspirin, 6 h after aspirin on day 1, and before aspirin on day 14. Bleeding times, plasma volume, and total volume increased significantly from before aspirin to after 6 h and 14 days (p < 0.0001 for all parameters) for all aspirin formulations. For day 1 before aspirin ingestion to 6 h later, both TX and PGI2 (p < 0.008) decreased significantly. 6 h after ingestion of aspirin on day 1 to day 14, both TX and PGI2 levels also significantly decreased (p < 0.0001). There was a highly significant decrease in PGI2 production on every other day aspirin schedules (p = 0.0001) particularly with 80 mg of aspirin, while the decrease in PGI2 production on daily aspirin was not significant (p = 0.10). The most favourable ratio of 6-keto-PGF1 alpha to TXB2 occurred with 80 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid ultrastructural changes in the dense tubular system following platelet activation.

The dense tubular system (DTS) functions to regulate platelet activation by sequestering or releasing calcium, similar to the sarcotubules of skeletal muscle. In resting platelets, the DTS exists as thin elongated membranes. Within 10 seconds of the addition of thrombin, platelets show a major ultrastructural change in their DTS: from the thin elongated form to a rounded vesicular form. These morphologic changes were demonstrated with two different stains and two different fixation methods. Platelets exposed to the calcium ionophore A23187 showed the same ultrastructural changes in the DTS. In contrast, the DTS remains in a thin elongated form when platelets are stimulated by the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and oleoylacetylglycerol (OAG). These morphologic changes may be related to the discharge of calcium from the DTS because this is stimulated by thrombin and A23187, but not by PMA. Preincubation of the platelets with the intracellular calcium chelator 5,5'-dimethyl-bis-(0-aminophenoxy)-ethane-N,N,N',N tetra acetic acid (BAPTA) largely prevented both the thrombin-induced rise in intracellular calcium and the changes in DTS morphology, suggesting that the changes in DTS morphology are secondary to the increase in cytosolic calcium. The results provide a morphologic correlate to existing biochemical evidence showing that the DTS is involved early during paltelet activation.

Blood pressure during pregnancy in Canadian Inuit: community differences related to diet.

OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted.

Dietary omega 3 fatty acids and gestational hypertension in the Inuit.

Blood pressure at the end of pregnancy and the incidence of pregnancy-induced hypertension were monitored in Inuit communities in the Keewatin region of the Northwest Territories. Communities with more fish and sea mammals in their diet had a lower blood pressure at the end of pregnancy and a lower incidence of gestational hypertension. The lower incidence of gestational hypertension was independent of other variables, including pregravida weight and parity. Cord blood phospholipid fatty acid analysis confirmed higher levels of eicosapentanoic acid, a fatty acid enriched in fish and sea mammals, in infants born to mothers from communities with higher fish in their diets.