Surgical Cancer Care in Safety-Net Hospitals: a Systematic Review.

BACKGROUND: Tertiary medical centers in the USA provide specialized, high-volume surgical cancer care, contributing standards for quality and outcomes. For the most vulnerable populations, safety-net hospitals (SNHs) remain the predominant provider of both complex and routine healthcare needs. The objective of this study was to evaluate access to and quality of surgical oncology care within SNHs. METHODS: A comprehensive and systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane Library databases to identify all studies (January 2000-October 2021) reporting the delivery of surgical cancer care at SNHs in the USA (PROSPERO #CRD42021290092). These studies describe the process and/or outcomes of surgical care for gastrointestinal, hepatopancreatobiliary, or breast cancer patients seeking treatment at SNHs. RESULTS: Of 3753 records, 37 studies met the inclusion criteria. Surgical care for breast cancer (43%) was the most represented, followed by colorectal (30%) and hepatopancreatobiliary (16%) cancers. Financial constraints, cultural and language barriers, and limitations to insurance coverage were cited as common reasons for disparities in care within SNHs. Advanced disease at presentation was common among cancer patients seeking care at SNHs (range, 24-61% of patients). Though reports comparing cancer survival between SNHs and non-SNHs were few, results were mixed, underscoring the variability in care seen across SNHs. CONCLUSIONS: These findings highlight barriers in care facing many cancer patients. Continued efforts should address improving both access and quality of care for SNH patients. Future models include a transition away from a two-tiered system of resourced and under-resourced hospitals toward an integrated cancer system.

Endothelial cell dysfunction during anoxia-reoxygenation is associated with a decrease in adenosine triphosphate levels, rearrangement in lipid bilayer phosphatidylserine asymmetry, and an increase in endothelial cell permeability.

BACKGROUND: Phosphatidylserine (PS) is normally confined in an energy-dependent manner to the inner leaflet of the lipid cell membrane. During cellular stress, PS is exteriorized to the outer layer, initiating a cascade of events. Because cellular stress is often accompanied by decreased energy levels and because maintaining PS asymmetry is an energy-dependent process, it would make sense that cellular stress associated with decreased energy levels is also associated with PS exteriorization that ultimately leads to endothelial cell dysfunction. Our hypothesis was that anoxia-reoxygenation (A-R) is associated with decreased adenosine triphosphate (ATP) levels, increased PS exteriorization on endothelial cell membranes, and increased endothelial cell membrane permeability. METHODS: The effect on ATP levels during A-R was measured via colorimetric assay in cultured cells. To measure the effect of A-R on PS levels, cultured cells underwent A-R and exteriorized PS levels and also total cell PS were measured via biofluorescence assay. Finally, we measured endothelial cell monolayer permeability to albumin after A-R. RESULTS: The ATP levels in cell culture decreased 27% from baseline after A-R (p < 0.02). There was over a twofold increase in exteriorized PS as compared with controls (p < 0.01). Interestingly, we found that during A-R, the total amount of cellular PS increased (p < 0.01). The finding that total PS changed twofold over normal cells suggested that not only is there a change in the distribution of PS across the cell membrane, but there may also be an increase in the amount of PS inside the cell. Finally, A-R increased endothelial cell monolayer permeability (p < 0.01). CONCLUSION: We found that endothelial cell dysfunction during A-R is associated with decreased ATP levels, increased PS exteriorization, and increased in monolayer permeability. This supports the idea that PS exteriorization may a key event during clinical scenarios involving oxygen lack and may 1 day lead to novel therapies in these situations.

Emergent Neurosurgical Management of a Rapidly Deteriorating Patient with Acute Intracranial Hemorrhage and Alcohol-Related Thrombocytopenia.

Alcohol intoxication is a common risk factor of traumatic brain injury (TBI) and carries a significant health-care burden on underserved patients. Patients with chronic alcohol use may suffer a spectrum of bleeding diatheses from hepatic dysfunction not well studied in the context of TBI. A feared sequela of TBI is the development of coagulopathy resulting in worsened intracranial bleeding. We report the clinical course of an intoxicated patient found down with blunt head trauma and concurrent alcoholic cirrhosis who was awake and responsive in the field. Hospital course was characterized by a rapidly deteriorating neurological examination with progressive subdural and subarachnoid hemorrhage and precipitating neurosurgical decompression and critical care management. Our experience dictates the need for timely consideration of the possibility of rapid deterioration from coagulopathic intracranial bleeding in the initial assessment of intoxicated patients with head trauma of unknown severity, for which a high index of suspicion for extra-axial hemorrhage should be maintained, along with the immediate availability of operating room and the necessary medical personnel.

The heart of the matter: utility of ultrasound of cardiac activity during traumatic arrest.

BACKGROUND: The clinical utility of determining cardiac motion on ultrasound has been reported for patients presenting in pulseless medical cardiac arrest. However, the relationship between ultrasound-documented cardiac activity and the probability of surviving pulseless electrical activity has not been examined in populations with trauma. We hypothesized that cardiac activity on ultrasound predicts survival for patients presenting in pulseless traumatic arrest. METHODS: We conducted a retrospective analysis at our university-based urban trauma center of adult patients with trauma, who were pulseless on hospital arrival. Results of cardiac ultrasound performed during trauma resuscitations were compared with the electrocardiogram (EKG) rhythm and survival. RESULTS: Among 318 pulseless patients with trauma, 162 had both EKG tracings and a cardiac ultrasound, and 4.3% of these 162 patients survived to hospital admission. Survival was higher for those with cardiac motion than for those without it (23.5% vs. 1.9% for patients with EKG electrical activity, p = 0.002, and 66.7% vs. 0% for patients without EKG electrical activity, p < 0.001). The sensitivity of ultrasound cardiac motion to predict survival to hospital admission was 86% (specificity, 91%; positive predictive value, 30%; negative predictive value, 99%). When examined by mechanism, sensitivity was 100% for the 111 patients with penetrating trauma and 75% for the 50 patients with blunt trauma. CONCLUSION: Survival in pulseless traumatic arrest is very low, but survival for patients with no cardiac motion on ultrasound is also exceedingly rare. Cardiac ultrasound had a negative predictive value approaching 100% for survival to hospital admission. For patients with prolonged prehospital cardiopulmonary resuscitation, ultrasound evaluation of cardiac motion in pulseless patients with trauma may be a rapid way to help determine which patients have no chance of survival in the setting of lethal injuries, so that futile resuscitations can be stopped.

A novel CT volume index score correlates with outcomes in polytrauma patients with pulmonary contusion.

BACKGROUND: Exact quantification of pulmonary contusion by computed tomography (CT) may help trauma surgeons identify high-risk populations. We hypothesized that the size of pulmonary contusions, measured accurately, will predict outcomes. Our specific aims were to (1) precisely quantify pulmonary contusion size using pixel analysis, (2) correlate contusion size with outcomes, and (3) determine the threshold contusion size portending complications. METHODS: Thoracic CTs of 106 consecutive polytrauma patients with pulmonary contusion were evaluated at a university-based urban trauma center. A novel CT volume index (CTVI) score was calculated based on the ratio of affected lung to total lung [slices of lung on CT × affected pixel region/lung pixel region × 0.45 (left side) + slices of lung on CT × affected pixel region/lung pixel region × 0.55 (right side)]. Multivariate analysis correlated CTVI and patient predictors' impact on outcomes. RESULTS: Of 106 polytrauma patients (mean ISS = 28 ± 1.2, AIS chest = 3.5 ± 0.1), 39 developed complications (acute respiratory distress syndrome [ARDS], pneumonia, and/or death). Mean CTVI was significantly higher in the group with complications (0.28 ± 0.03 versus 17 ± 0.02, P = 0.01). By multivariate analysis, CTVI predicted longer ICU LOS (R(2) = 0.84, P < 0.01). A receiver operating curve (ROC) analysis identified a CTVI threshold score of 0.2 (AUC 0.67, P < 0.01) for developing pneumonia, ARDS or death. Patients with CTVI scores of 0.2 or more had longer hospitalization, longer ICU LOS, more ventilator days, and developed pneumonia (P < 0.01). CONCLUSIONS: Higher CTVI scores predicted prolonged ICU LOS across all sizes of pulmonary contusion. Pulmonary contusion volumes greater than 20% of total lung volume specifically identifies patients at risk for developing complications.

Correlation between IVC dimensions and volume status on CT scan.

BACKGROUND: End points of resuscitation in trauma patients are difficult to define. The size of the inferior vena cava (IVC) on CT scan may accurately indicate volume status and guide resuscitation efforts. Our hypothesis was that IVC "flatness" on CT scan reflects volume status in hemodynamically normal trauma patients. METHODS: The study population was drawn from a database of trauma patients who had abdominal CT scans and lactate levels drawn on arrival. Lactate was chosen as a marker of volume status since hypotensive patients were unlikely to undergo CT. Anteroposterior (AP) and transverse (TV) diameters of the IVC were measured at the suprarenal and infrarenal locations. A flatness index was calculated for each location (TV ÷ AP) and this value was correlated with heart rate, blood pressure, and lactate. RESULTS: There was no difference in IVC flatness at the suprarenal or infrarenal position for patients with an elevated lactate compared with those with a normal lactate: 1.54 ± 0.18 versus 1.43 ± 0.08 (P = 0.2) suprarenal and 1.54 ± 0.46 versus 1.68 ± 0.58 (P = 0.4) infrarenal. IVC flatness at the suprarenal location weakly correlated with blood pressure (r = -0.29). IVC flatness did not correlate with blood pressure at the infrarenal location (r = -0.1). IVC flatness did not correlate with heart rate (P > 0.3) or age (P > 0.2). CONCLUSION: These results did not demonstrate a correlation between IVC flatness and the markers of intravascular volume of heart rate, blood pressure, or lactate. IVC flatness on CT scan is not a valid indicator of volume status in hemodynamically normal trauma patients.

Sonographic optic nerve sheath diameter as an estimate of intracranial pressure in adult trauma.

BACKGROUND: Intracranial pressure (ICP) is currently measured with invasive monitoring. Sonographic optic nerve sheath diameter (ONSD) may provide a noninvasive estimate of ICP. Our hypothesis was that bedside ONSD accurately estimates ICP in acutely injured patients. The specific aims were (1) to determine the accuracy of ONSD in estimating elevated ICP, (2) to correlate ONSD and ICP in unilateral and bilateral head injuries, and (3) to determine the effect of ICP monitor placement on ONSD measurements. MATERIALS AND METHODS: A blinded prospective study of adult trauma patients requiring ICP monitoring was performed at a University-based urban trauma center. The ONSD was measured by ultrasound pre- and post-placement of an ICP monitor (Camino Bolt or Ventriculostomy). RESULTS: One-hundred fourteen measurements were obtained in 10 trauma patients requiring ICP monitoring. Pre- and post-ONSD were compared with side of injury in the presence of an ICP monitor. ROC analysis demonstrated ONSD poorly estimates elevated ICP (AUC = 0.36). Overall sensitivity, specificity, PPV, NPV, and accuracy for estimating ICP with ONSD were 36%, 38%, 40%, 16%, and 37%. Poor correlation of ONSD to ICP was observed with unilateral (R(2) = 0.45, P < 0.01) and bilateral (R(2) = 0.21, P = 0.01) injuries. ICP monitor placement did not affect ONSD measurements on the right (P = 0.5), left (P = 0.4), or right and left sides combined (P = 0.3). CONCLUSIONS: Sonographic ONSD as a surrogate for elevated ICP in lieu of invasive monitoring is not reliable due to poor accuracy and correlation.

Endothelin-1 attenuates increases in hydraulic conductivity due to platelet-activating factor via prostacyclin release.

We previously showed that endothelin-1 (ET-1) and prostacyclin (PGI(2)) similarly attenuate increases in microvascular permeability induced by platelet-activating factor (PAF). This led us to hypothesize that ET-1 attenuates trans-endothelial fluid flux during PAF through PGI(2) release. We tested this hypothesis in three phases. First, bovine pulmonary artery endothelial cells were exposed to 0.008-8 µM ET-1 and assayed for PGI(2) release. Second, to determine whether increased transmonolayer flux after PAF could be attenuated by ET-1 or PGI(2) and reversed by PGI(2) synthesis inhibition or PGI(2) receptor blockade, we measured endothelial cell transmonolayer flux after cells were exposed to 10 nM PAF plus 10 µM PGI(2) or 80 pM ET-1, with or without 500 µM tranylcypromine (PGI(2) synthase inhibitor) or 20 µM CAY-10441 (PGI(2) receptor blocker). Finally, hydraulic conductivity (L(p)) was measured in rat mesenteric venules in vivo after exposure to 10 nM PAF and 80 pM ET-1 with or without tranylcypromine (100 and 500 µM) or CAY-10441 (2 and 20 µM). We found that in vitro, ET-1 stimulated a dose-dependent increase in PGI(2) production (from 126 to 217 pg/ml, P < 0.01). Compared with PAF alone, PGI(2) plus PAF and ET-1 plus PAF decreased transmonolayer flux similarly by 52 and 46%, respectively (P < 0.01), while tranylcypromine and CAY-10441 reversed these effects by 92 and 47%, respectively (P < 0.05). In vivo, PAF increased L(p) fourfold (P < 0.01) and ET-1 attenuated this effect by 83% (P < 0.01). Tranylcypromine and CAY-10441 reversed the ET-1 attenuation in L(p) during PAF by 55 and 45%, respectively (P < 0.01). We conclude that ET-1 may stimulate endothelial cell PGI(2) release to attenuate the increases in transmonolayer flux and hydraulic conductivity secondary to PAF.

Insurance coverage is associated with mortality after gunshot trauma.

BACKGROUND: Poor access to adequate health care coverage is associated with poor outcomes for many chronic medical conditions. We hypothesized that insurance coverage is also associated with mortality after gunshot trauma. STUDY DESIGN: The trauma records for gunshot victims and their insurance status were reviewed at our center from January 1998 to December 2007. Patient demographics (age, gender, race, and insurance coverage), injury severity, hospital care (operations and radiographic studies), and in-hospital mortality were analyzed. RESULTS: There were 2,164 gunshot trauma activations reviewed during the study period. One-quarter (n = 544) of these patients had insurance and three-quarters (n = 1,620) were uninsured. The in-hospital mortality rate was significantly higher for uninsured patients than for insured patients (9% vs 6%, p = 0.02). After controlling for age, gender, race, and injury severity by logistic regression analysis, the odds ratio for death of uninsured patients was 2.2 (95% CI 1.1 to 4.5). Insured patients did not differ from uninsured patients with respect to mean Injury Severity Score ([ISS] 12.2 +/- 10.7 vs 12.6 +/- 12.4, p = 0.56); similar percentages of patients were severely injured (ISS 16 to 24, 17% vs 15%, p = 0.19) and most severely injured (ISS > 24, 15% vs 16%, p = 0.68). Insured patients did not differ from uninsured patients with respect to use of radiographic imaging (53% vs 50%, p = 0.15) or operative intervention (37% vs 35%, p = 0.35). CONCLUSIONS: Despite similar injury severity, uninsured trauma patients were more likely to die after gunshot injury than insured patients. This difference could not be attributed to demographics or hospital resource use. Insurance coverage may reflect the many social determinants of health. Improving the social determinants of health in patients affected by violent trauma may be a step toward improving outcomes after trauma.

Ghrelin decreases microvascular leak during inflammation.

BACKGROUND: Obesity is a risk factor for poor outcomes after trauma, and circulating levels of ghrelin are decreased in obese patients. We hypothesized that ghrelin modifies microvascular permeability. The purposes of this study were to determine (1) the effect of ghrelin on microvascular permeability, (2) the effect of ghrelin on microvascular permeability during lipopolysaccharide (LPS)-induced inflammation, (3) the involvement of the growth hormone secretagogue receptor (GHS-R1a) cell receptor, and (4) the involvement of nuclear factor kappa B (NF-kappaB). METHODS: Hydraulic permeability (Lp), a measure of transendothelial fluid leak, was measured in rat mesenteric postcapillary venules. Lp was measured during continuous administration of (1) ghrelin (3 micromol/L), (2) ghrelin and systemic LPS (10 mg/kg), (3) the GHS-R1a receptor antagonist, (D-Arg1 D-Phe5 D-Trp7,9 Leu11)-substance P (9 micromol/L) plus ghrelin and LPS, and (4) an NF-kappaB inhibitor, parthenolide (10 micromol/L) plus ghrelin and LPS. RESULTS: Ghrelin alone had no effect (p > 0.7). Compared with LPS alone, ghrelin plus LPS decreased Lp (Lp: ghrelin + LPS = 1.60 +/- 0.16 vs. LPS = 2.27 +/- 0.14, p < 0.006). The GHS-R1a ghrelin receptor antagonist blunted the effect of ghrelin by 86% during LPS-induced inflammation (Lp: ghrelin + LPS = 1.60 +/- 0.16 vs. ghrelin antagonist + ghrelin + LPS = 2.17 +/- 0.27, p < 0.018). NF-kappaB inhibition did not influence the initial increased microvascular leak effect of ghrelin (p > 0.8). CONCLUSIONS: Although ghrelin has no effect on basal microvascular permeability, it has a biphasic effect with an overall decrease in microvascular permeability during LPS-induced inflammation through the GHS-R1a receptor, independent of NF-kappaB. Ghrelin is a key mediator of inflammation and may contribute to the increased morbidity and mortality in obese trauma patients.

Endothelin 1 and prostacyclin attenuate increases in hydraulic permeability caused by platelet-activating factor in rats.

We have previously documented that endothelin 1 (ET-1) and prostacyclin (PGI2) decrease basal state hydraulic permeability (Lp). The aim of this study was to investigate the ability of ET-1 and PGI2 to modulate transendothelial fluid flux during situations in which Lp was artificially elevated with platelet-activating factor (PAF). We hypothesized that ET-1 and PGI2 administration before PAF exposure would prevent the increase in Lp secondary to PAF. In addition, in a potentially more clinically relevant situation, we also hypothesized that ET-1 and PGI2 administration after PAF exposure would attenuate the increase in Lp secondary to PAF. Microvascular Lp was measured in rat mesenteric postcapillary venules. Exposure to 10 nM PAF increased Lp 4-fold (P < 0.001). If the administration of 80 pM ET-1 or 10 microM PGI2 was completed before PAF exposure, no PAF-associated increase in Lp was observed (P < 0.001). The administration of ET-1 or PGI2 after PAF exposure attenuated the peak increase in Lp caused by PAF alone by 55% and 57%, respectively (P < 0.001). We conclude that ET-1 and PGI2 administration before PAF exposure prevents PAF-induced elevations in Lp, and in a more clinically relevant situation, ET-1 and PGI2 administered after PAF exposure attenuate the PAF-induced increase in Lp. Endothelin 1 and PGI2 receptors may provide important therapeutic targets for decreasing the microvascular fluid leak-associated morbidity resulting from shock and sepsis.

A different view of lactate in trauma patients: protecting the injured brain.

BACKGROUND: The relationship between lactate and head injury is controversial. We sought to determine the relationship between initial serum lactate, severity of head injury, and outcome. We hypothesized that lactate is elevated in head injured patients, and that initial serum lactate increases as the severity of head injury increases. Furthermore, lactate may be neuroprotective and improve neurologic outcomes. MATERIALS AND METHODS: We identified normotensive adult patients over a 6-y period at our university-based urban trauma center with isolated blunt head injury. We performed univariate and multivariate analysis to examine the relationship between lactate and Glasgow coma scale (GCS). The correlation of admission lactate with survival and neurologic function was also examined. RESULTS: There were 555 patients who met study criteria. While controlling for injury severity score and age, increased lactate was associated with more severe head injury (P<0.0001). The admission lactate was 2.2+/-0.07, 3.7+/-0.7, and 4.7+/-0.8 mmol/L in patients with mild, moderate, and severe head injury respectively (P<0.01). Patients with moderate or severe head injury and an admission lactate>5 were more likely to have a normal mental status on discharge (P<0.0001). CONCLUSIONS: In normotensive isolated head injured patients, there was an increase in serum lactate as head injuries became more severe. Since lactate is a readily available fuel source of the injured brain, this may be a mechanism by which brain function is preserved in trauma patients. Elevations in lactate due to anaerobic metabolism in trauma patients may have beneficial effects by protecting the brain during injury.

Expedited treatment of lower extremity gunshot wounds.

BACKGROUND: Patients with isolated lower extremity gunshot wounds are currently admitted for observation and often undergo angiography. We hypothesized that if such patients have a normal ankle-brachial index (ABI), they can be discharged safely from the emergency department without invasive imaging or admission. STUDY DESIGN: We retrospectively reviewed the records of hemodynamically stable patients with isolated lower extremity gunshot wounds seen at our urban, university-based trauma center and who were discharged from the emergency department. Evaluation consisted of determining which patients were hemodynamically normal, had no fractures, and had an ABI > or =0.9. Patients with an ABI <0.9 underwent CT angiography. We then applied this practice algorithm prospectively, adding evaluation of high probability proximity wounds by ultrasonography or CT angiography to rule out missed injuries. RESULTS: The retrospective review identified 182 patients who met our criteria. None had bleeding, limb ischemia, or limb loss. The specificity of the evaluation in the retrospective study to predict safe discharge was 100%, with a negative predictive value of 98%. There were 90 patients in the prospective study. Bleeding, limb ischemia, or limb loss did not develop in any patient. The prospective algorithm for predicting safe discharge home had a 100% positive predictive value and 98% negative predictive value. Using this algorithm, costs were 992 dollars per patient. If every patient received ultrasonography or CT angiography, it would have been 1,135 dollars or 4,632 dollars, respectively, per patient. CONCLUSIONS: Hemodynamically normal patients with lower extremity gunshot wounds without fracture and an initial ABI > or =0.9 can be discharged safely from the emergency department without additional diagnostic imaging, potentially saving health care costs.

Single-contrast computed tomography for the triage of patients with penetrating torso trauma.

BACKGROUND: We have used single-contrast (intravenous contrast only) computed tomography (SCCT) for triaging hemodynamically stable patients with penetrating torso trauma. We hypothesized that SCCT safely determines the need for operative exploration. Furthermore, trauma surgeons without specialized training in body imaging can accurately apply this modality. METHODS: We retrospectively reviewed the records of patients with penetrating torso injuries at a university-based urban trauma center to establish the accuracy of SCCT in determining the need for exploratory laparotomy. The scan was considered positive or negative with respect to the need for exploratory laparotomy as documented by the attending surgeon, who may have considered the read of the on call radiologist if available. In a separate study, four trauma surgeons independently reviewed 42 SCCT scans to establish whether the scans alone could be used to determine whether operative exploration was necessary. RESULTS: Between 1997 and 2008, 306 hemodynamically stable patients with penetrating torso trauma were triaged by SCCT. Overall, SCCT predicted the need for laparotomy with 98% sensitivity and 90% specificity. The positive predictive value was 84% and the negative predictive value (NPV) was 99%. In the 222 patients with gunshot wounds, SCCT had 100% sensitivity and 100% NPV. In the 84 patients with stab wounds, SCCT had 92% sensitivity and 97% NPV. Trauma surgeon agreement in the retrospective review of 42 computed tomography scans was "nearly perfect": positive predictive value was 93% and NPV was 92% for determining the need for exploratory laparotomy surgery. CONCLUSIONS: SCCT is safe and effective for triaging hemodynamically stable patients with penetrating torso trauma. It successfully determined the need for operative intervention with appropriate clinical accuracy without the additional costs, morbidity, and delay of oral and rectal contrast. Trauma surgeons can reproducibly interpret SCCT with high-predictive accuracy as to whether patients with penetrating torso trauma require operative exploration.

Despite the increasing use of nonoperative management of firearm trauma, shotgun injuries still require aggressive operative management.

BACKGROUND: The energy dissipation between gunshot and shotgun blasts is very different. Injuries from shotgun blasts vary depending on the distance of the victim from the shooter, the choke of the shotgun, the pellet load, and the wad of the ammunition. We postulated that gunshot and shotgun blasts create different injury patterns that dictate different treatment plans. METHODS: Medical records of patients with gunshot and shotgun trauma were reviewed from 1998 through 2007 at our university-based trauma center. Statistical comparisons were made via Fisher's test or t-test calculations. RESULTS: We evaluated 2833 patients injured by firearms; of these 61 had shotgun wounds (2.2%). The remainder sustained gunshot wounds. Mortality between shotgun and gunshot trauma patients was similar (7% versus 9%, respectively, P=0.8). There was no difference in the mean Injury Severity Score (ISS) (13.7+/-1.6 versus 12.9+/-0.2; P=0.6). Overall, 61% of patients underwent operative intervention after shotgun injuries versus 36% of patients with gunshot wounds (P<0.0001). Patients surviving shotgun injuries had a longer length of stay (10.1+/-2.0 d versus 5.9+/-0.21, P<0.05). CONCLUSIONS: Although the injury severity was similar, injuries from shotguns required more operations and resource utilization. Shotgun blasts can create impressive superficial injuries as well as significant deep organ damage. An aggressive operative approach to managing shotgun trauma is advantageous.

Lipoxin a(4) attenuates microvascular fluid leak during inflammation.

BACKGROUND: The release of proinflammatory cytokines during inflammation disturbs the endothelial barrier and can initiate significant intravascular volume loss. Proinflammatory cytokines also induce the expression of anti-inflammatory mediators, such as lipoxin, which promote the resolution of inflammation. Our hypothesis is that lipoxin A(4) (LXA(4)) reverses the increased microvascular fluid leak observed during inflammatory conditions. MATERIALS AND METHODS: Microvascular fluid leak (L(p)) was measured in rat mesenteric venules using a micro-cannulation technique. L(p) was measured under the following conditions: (1) LXA(4) (100 nM) alone (n = 5), (2) LXA(4) (100 nM) administered after endothelial hyperpermeability induced by a continuous perfusion of 10 nM platelet activating factor (PAF) (n = 5), (3) LXA(4) (100 nM) perfused after inflammation induced by a systemic bolus of 10 mg/kg lipopolysaccharide (LPS) (n = 5), and (4) LXA(4) (100 nM) perfused after LPS-induced inflammation during inhibition of c-Jun N-terminal kinase (n = 4). RESULTS: LXA(4) alone slightly increased L(p) from baseline (L(p)-baseline = 1.05 +/- 0.03, L(p)-LXA(4) = 1.55 +/- 0.04; P < 0.0001). PAF increased L(p) 4-fold (L(p)-baseline = 1.20 +/- 0.10, L(p)-PAF = 4.49 +/- 0.95; P < 0.0001). LXA(4) administration after PAF decreased L(p) 66% versus PAF alone (from 4.49 +/- 0.95 to 1.54 +/- 0.13; P = 0.0004). LPS-induced inflammation increased L(p) over 2-fold (L(p)-baseline = 1.05 +/- 0.03, L(p)-LPS = 2.27 +/- 0.13; P < 0.0001). LXA(4) administration after LPS decreased L(p) 42% versus LPS alone (from 2.27 +/- 0.13 to 1.31 +/- 0.05; P < 0.0001). The effect of c-Jun N-terminal kinase inhibition during LPS-induced inflammation attenuated the decrease in leak cause by LXA(4) by 51% (P = 0.0002). CONCLUSION: After either LPS or PAF, LXA(4) attenuated the intravascular volume loss caused by these inflammatory mediators. The activity of LXA(4) may be partly mediated by the c-Jun N-terminal kinase signaling pathway. These data support an anti-inflammatory role for LXA(4) and suggests a potential pharmacologic role for LXA(4) during inflammation.

Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation.

Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L(p)) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L(p) was measured. Second, after systemic LPS injection, L(p) was measured after subsequent perfusion with GLP-1. Thirdly, L(p) was measured after LPS injection and perfusion with GLP-1+GLP-1 receptor antagonist. Lastly, L(p) was measured after LPS injection and perfusion with GLP-1+inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC)+/-SEM. GLP-1 had no effect on L(p) (AUC: baseline=27+/-1.4, GLP-1=1+/-0.4, p=0.08). LPS increased L(p) two-fold (AUC: LPS=54+/-1.7, p<0.0001). GLP-1 reduced the LPS increase in L(p) by 75% (AUC: LPS+GLP-1=34+/-1.5, p<0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+antagonist=46+/-2.0, p<0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+cAMP inhibitor=46+/-1.5, p<0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS+GLP-1+PKA inhibitor=56+/-1.5, p<0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.

Transfusion, not just injury severity, leads to posttrauma infection: a matched cohort study.

Blood transfusion has been associated with infection; however, the collinearity of injury severity has not been clearly addressed to show a direct relationship. Using more rigorous analysis, we aimed to untangle the effect of injury severity from transfusion leading to sepsis. We hypothesized that blood transfusion independently increases infection in massively transfused versus nontransfused patients with matched Injury Severity Scores (ISSs). We performed a matched cohort study measuring infection rates in trauma patients receiving massive transfusion. Control subjects were contemporaneous patients with matched ISS receiving no blood. Infection was defined as intraperitoneal or intrathoracic abscesses, pneumonia, urinary tract infection, or bacteremia. Multivariate logistic and univariate analysis was completed. Infection rate was 61 per cent in 44 transfused patients versus 20 per cent in 44 control subjects (P = 0.001). Odds of infection were eightfold greater in transfused patients (OR, 7.97; 95% CI, 2.3 to 27.5; P < 0.001) independent of ISS, Glasgow Coma Scale, mechanism, and age. Infection was most associated with transfusion of packed red blood cells (PRBCs), although transfusion of other blood products had strong collinearity with PRBCs. Transfused patients had eight times the risk of infection independent of ISS; this appears to be the result of PRBC transfusion. Modifying the ratio of components in transfusion protocols favoring plasma may cause less infection after injury.

The number of gunshot wounds does not predict injury severity and mortality.

It is presumed that as the number of gunshot wounds (GSWs) increases, so do the Injury Severity Score (ISS) and mortality risk. We hypothesized that the number of bullet wounds relates to ISS and death; however, a single GSW to the head is ominous. We reviewed the charts of all GSW patients admitted to a trauma center from 2004 to 2006 (n = 531). We analyzed patient demographics, ISS, and mortality. There was no correlation with the number of GSWs with either ISS or mortality. There was only a 0.3 per cent increased risk of death for each additional GSW (r2 = 0.12). Patients with a single GSW versus multiple GSWs had no difference in mortality (9.1 vs 8.4%, P = 0.8). A single GSW to the head carried a 50 per cent mortality risk. For those who sustained both head and body GSWs, each additional GSW did not increase mortality (r2 = 0.007). Our study shows that the number of GSWs has no affect on mortality or ISS. Internal triage and management of gunshot victims should not be affected by the categorization of patients as having a single versus multiple GSWs.

The effect of hypoxia, reoxygenation, ischemia, and reperfusion on hydraulic permeability in rat mesenteric venules.

Little is known regarding the effects of I/R on hydraulic permeability (Lp). We sought to compare the individual influences of hypoxia, ischemia, reoxygenation, and reperfusion on Lp. We hypothesized that (1) hypoxia increases Lp; (2) reoxygenation further increases Lp; (3) ischemia results in greater increases in Lp compared with hypoxia; (4) reperfusion causes additional increases in Lp compared with hypoxia, ischemia, and reoxygenation; and (5) xanthine oxidase (XO) and white blood cell adherence play important roles in hypoxia, ischemia, and reperfusion. Hydraulic permeability was measured by an in vivo microcannulation technique during hypoxia, reoxygenation, ischemia, and reperfusion in rat mesenteric postcapillary venules. Additional rats were fed a Tungsten-enriched diet to inhibit XO activity, and the studies were repeated. White blood cell adherence was also documented. Hypoxia and ischemia both increased Lp 2-fold from baseline levels (P < 0.001). Reoxygenation did not alter Lp compared with 15 min of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased Lp 6-fold (P < 0.001). Reperfusion after ischemia also increased Lp 6-fold (P < 0.001). Inhibition of XO had no effect on the increase in Lp after both hypoxia and ischemia. However, inhibition of XO attenuated the 6-fold increase in Lp observed during reperfusion after both hypoxia and ischemia by approximately 50% (P < 0.001). White blood cell adherence increased during reperfusion but not hypoxia or ischemia. The complexity of I/R injury makes it a difficult clinical scenario to model for research. We have demonstrated in an in vivo model that hypoxia and ischemia increase Lp similarly, and that reperfusion has a profound deleterious effect on Lp. These changes in Lp seem to be XO and white blood cell dependent.