SummaryResuscitation from hemorrhagic shock induces profound changes in the physiologic processes of many tissues and activates inflammatory cascades that include the activation of stress transcriptional factors and upregulation of cytokine synthesis. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that the inducible nitric oxide synthase (iNOS) is expressed during hemorrhagic shock. We postulated that nitric oxide production from iNOS would participate in proinflammatory signaling. Using the iNOS inhibitor N 6 -(iminoethyl)-l -lysine or iNOS knockout mice we found that the activation of the transcriptional factors nuclear factor B and signal transducer and activator of transcription 3 and increases in IL-6 and G-CSF messenger RNA levels in the lungs and livers measured 4 h after resuscitation from hemorrhagic shock were iNOS dependent. Furthermore, iNOS inhibition resulted in a marked reduction of lung and liver injury produced by hemorrhagic shock. Thus, induced nitric oxide is essential for the upregulation of the inflammatory response in resuscitated hemorrhagic shock and participates in end organ damage under these conditions. H emorrhagic shock initiates an inflammatory response characterized by the upregulation of cytokine expression (1) and accumulation of neutrophils (2) in a variety of tissues. These changes are prominent in the lungs and liver and are likely to contribute to end organ damage and resultant dysfunction after shock. The mechanisms by which hemorrhage triggers this inflammatory response remain poorly understood. Heightened adrenergic activity (3) and systemic release of proinflammatory agents from the gut (4, 5) have been hypothesized to contribute to acute lung injury after hemorrhage. In addition, reactive radicals are produced after ischemia/reperfusion and resuscitation from hemorrhagic shock, and have been implicated in a number of signal transduction pathways (6).Among the important radicals produced during hemorrhagic shock is the bioregulatory molecule nitric oxide (NO) 1 generated catalytically by three enzymes collectively termed NO synthases. We (7) and others (8) have shown that the inflammatory or inducible NO synthase (iNOS or NOS2) is upregulated in both the lungs and liver during shock. Therefore, this isoform may be capable of catalyzing the sustained production of NO after the tissue reperfusion associated with fluid resuscitation. NO can have both direct effects on cell signaling as well as indirect actions mediated by the reaction products formed when NO interacts with other molecules such as oxygen or superoxide (9). We hypothesized that enhanced NO production resulting from iNOS expression would contribute to proinflammatory signaling in hemorrhagic shock. Hemorrhagic shock experiments were therefore carried out in rats treated with the iNOS-selective inhibitor N 6 -(iminoethyl)-l -lysine (L-NIL; reference 10) and mice genetically deficient in iNOS. We report here that iNOS inhibition or deficiency prevents t...

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IntroductionSingle-pass, whole-body computed tomography (pan-scan) remains a controversial intervention in the early assessment of patients with major trauma. We hypothesized that a liberal pan-scan policy is mainly an indicator of enhanced process quality of emergency care that may lead to improved survival regardless of the actual use of the method.MethodsThis retrospective cohort study included consecutive patients with blunt trauma referred to a trauma center prior to (2000 to 2002) and after (2002 to 2007) the introduction of a liberal single-pass pan-scan policy. The overall mortality between the two periods was compared and stratified according to the availability and actual use of the pan-scan. Logistic regression analysis was employed to adjust mortality estimates for demographic and injury-related independent variables.ResultsThe study comprised 313 patients during the pre-pan-scan period, 223 patients after the introduction of the pan-scan policy but not undergoing a pan-scan and 608 patients undergoing a pan-scan. The overall mortality was 23.3, 14.8 and 7.9% (P < 0.001), respectively. By univariable logistic regression analysis, both the availability (odds ratio (OR) 0.57, 95% confidence interval (CI): 0.36 to 0.90) and the actual use of the pan-scan (OR 0.28, 95% CI: 0.19 to 0.42) were associated with a lower mortality. The final model contained the Injury Severity Score, the Glasgow Coma Scale, age, emergency department time and the use of the pan-scan. 2.7% of the explained variance in mortality was attributable to the use of the pan-scan. This contribution increased to 7.1% in the highest injury severity quartile.ConclusionsIn this study, a liberal pan-scan policy was associated with lower trauma mortality. The causal role of the pan-scan itself must be interpreted in the context of improved structural and process quality, is apparently moderate and needs further investigation with regard to the diagnostic yield and changes in management decisions. (The Pan-Scan for Trauma Resuscitation [PATRES] Study Group, ISRCTN35424832 and ISRCTN41462125)

Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

The functional results demonstrate a biphasic response in the suppression of muscle activity after surgical manipulation. Regression analysis (r2 = 0.998) of the temporal development of leukocyte infiltration and the protracted phase of muscle inhibition provides evidence for a correlation between cellular inflammation and postoperative dysmotility.

Hemorrhagic shock (HS) results in the initiation of an inflammatory cascade that is critical for survival following successful resuscitation. We identified a complex sequence of molecular events including shock-dependent and reperfusion-dependent responses that offer a new comprehensive approach for consequences of HS. Shock-dependent initializing mechanisms include the induction of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and CD14 and play a catalyzing role for subsequent phenotypic changes following resuscitation. The early immediate response genes iNOS and COX-2 promote the inflammatory response by the rapid and excessive production of nitric oxide (NO) and prostaglandins. The transcription factor hypoxia-inducible factor-1 (HIF-1) may regulate the induction of iNOS during the ischemic phase of shock. NO is an important signaling molecule which is involved in redox-sensitive mechanisms including the downstream activation of nuclear factor (NF)-kappaB. NO-dependent NF-kappaB activation promotes the induction of inflammatory cytokine expression during the reperfusion phase. Peroxynitrite-mediated direct toxicity and NO-mediated inflammatory toxicity contribute to organ injury. Patients suffering consequences of severe HS are susceptible to systemic inflammation, organ injury, and mortality if physiologic and therapeutic mechanisms are ineffective in limiting the activation of the inflammatory cascade.

I/R injury evokes a molecular and cellular inflammatory response within the intestinal muscularis that is associated with a subsequent decrease in intestinal motility.

BACKGROUND:: The periarticular medial clavicle fracture is a rare injury and can be treated conservatively in the majority of cases. However, up to 8% of the patients develop symptomatic nonunion, and fracture dislocation correlates with the number of poor functional results. Operative treatment may be beneficial in these cases. Studies with large series of operated patients are still missing. METHODS:: We investigated 10 patients with operative treatment of periarticular medial clavicle fractures. Preoperative X-ray or computed tomography scan was obtained, and follow-up assessment was performed at determined intervals, including physical examination and X-ray evaluation of bone healing. Finally, functional assessment was carried out from September 2009 to July 2010 using the Disabilities of the Arm, Shoulder and Hand score. RESULTS:: All operated patients had displaced periarticular medial clavicle fractures. A direct surgical approach was performed, and denudation of the bone fragments was avoided. In 8 of 10 cases, we used locking plates, preferentially the T-locking plate. In 6 of 10 patients, three screws were placed in the medial fragment or the sternum. The arm was immobilized in a sling for 2 weeks to 3 weeks, followed by careful passive and increasing active motion exercises. In 9 of 10 operated patients, we observed fracture healing and good functional results. Two patients with paraplegia/tetraplegia were excluded from final assessment but demonstrated fracture healing. In one case, we observed early material loosening caused by misused locking system and wound infection. CONCLUSIONS:: Operative treatment can be considered for periarticular, dislocated medial-end clavicle fractures. Computed tomography scan can be useful for operative planning and is mostly performed in patients with multiple injuries. Locking plates, such as the T-locking plate or the pilon reconstruction plate, are preferred devices. For rigid fixation, at least three locking screws should be placed in the medial bone fragment. The plate can be removed 18 months after osteosynthesis.