PubMed · 14864276
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R MEYER-WILDISEN. 1951-07-19. [On gallbladder perforation].. https://pubmed.ncbi.nlm.nih.gov/14864276/
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Although previous studies have shown that flutamide improves cardiovascular function after trauma-hemorrhage, the mechanisms responsible for the salutary effect remain unknown. We hypothesized that flutamide mediates its beneficial effects via an estrogen-dependent pathway through upregulation of peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1). PGC-1, a key regulator of cardiac mitochondrial ATP production, induces mitochondrial DNA (mtDNA)-encoded genes such as cytochrome-c oxidase (COX) subunit I, II, and III (COX I, COX II, and COX III), which regulates mitochondrial oxidative phosphorylation. To test this hypothesis, male rats underwent trauma-hemorrhage (mean arterial pressure of 35-40 mmHg for approximately 90 min) followed by resuscitation. At the onset of resuscitation, rats received vehicle, flutamide (25 mg/kg body wt), flutamide in combination with estrogen receptor (ER) antagonist ICI-182,780 (3 mg/kg body wt), or ICI-182,780 alone. Flutamide administration after trauma-hemorrhage restored the depressed cardiac function and increased cardiac testosterone, estrogen levels, and aromatase activity. These increases were accompanied by normalized cardiac ER-alpha and ER-beta protein levels, PGC-1, and COX I mRNA expression, mitochondrial COX activity, and ATP contents. However, cardiac dihydrotestosterone, 5alpha-reductase II, androgen receptor protein levels, and mtDNA-encoded genes COX II and COX III were unaffected by flutamide treatment. The flutamide-mediated restoration of cardiac function, the increases in aromatase activity and estrogen levels, ER-alpha, ER-beta, PGC-1, COX I, COX activity, and ATP contents were, however, abolished when ER antagonist ICI-182,780 was administrated along with flutamide. These findings suggest that the salutary effect of flutamide on cardiac function after trauma-hemorrhage is mediated via an estrogen-dependent pathway through upregulation of PGC-1.
The results of extensive and prolonged surgical procedures performed in multi trauma patients are often poor. These patients may develop the lethal combination of metabolic acidosis, coagulopathy and hypothermia, which reduces their physiological reserve capacity. The 'damage control surgery' (DCS) approach is known to reduce the mortality rate in multi trauma patients. DCS consists of a short primary operation to control bleeding and prevent contamination. Thereafter, resuscitation is performed in the intensive care unit. Finally, reoperation and definitive repair of lesions are done.
PURPOSE: To study whether compliance with methodological standards affected the reported accuracy of screening ultrasonography (US) for trauma. MATERIALS AND METHODS: Meta-analysis was conducted of prospective investigations in which US was compared with any diagnostic reference test in patients with suspected abdominal injury. Reports were retrieved from electronic databases without language restrictions; added information was gained with manual search. Two reviewers independently assessed methodological rigor by using 27 items contained in the Standards for Reporting of Diagnostic Accuracy (STARD) checklist and the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QUADAS) instrument. Inconsistencies were resolved by means of consensus. Summary receiver operating characteristics and random-effects meta-regression were used to model the effect of methodological standards and other study features on US accuracy. RESULTS: A total of 62 trials, which included a total of 18,167 participants, were eligible for meta-analysis. The average proportion of men or boys was 71.7%, the mean age was 30.6 years +/- 10.8 (standard deviation), and the mean injury severity score was 16.7 +/- 8.3. The prevalence of abdominal trauma was 25.1% (95% confidence interval [CI]: 21.1%, 29.1%). Pooled overall sensitivity and specificity of US were 78.9% (95% CI: 74.9%, 82.9%) and 99.2% (95% CI: 99.0%, 99.4%), respectively. Varying end points (hemoperitoneum or organ damage) did not change these results. US accuracy was much lower in children (sensitivity, 57.9%; specificity, 94.3%). Strong heterogeneity was observed in sensitivity, whereas specificity remained constant across trials. There was evidence of publication bias. Initial interobserver agreement with methodological standards ranged from poor (kappa = 0.03, independent verification of US findings) to perfect (kappa = 1.00, sufficiently short interval between US and reference test). By consensus, studies fulfilled a median of 13 methodological criteria (range, five to 20 criteria). In investigations that lacked individual methodological standards, researchers overestimated pooled sensitivity, with predicted differences of 9%-18%. The use of a single reference test, specification of the number of excluded patients, and calculation of CIs independently contributed to predicted sensitivity in a multivariate model. In 16 investigations (1309 subjects), a single reference test was used, which provided a combined sensitivity of 66.0% (95% CI: 56.2%, 75.8%). CONCLUSION: Bias-adjusted sensitivity of screening US for trauma is low. Adherence to methodological standards included in appraisal instruments like STARD and QUADAS is crucial to obtain valid estimates of test accuracy.