John Y. Cha

Cytokines Link Toll-Like Receptor 4 Signaling to Cardiac Dysfunction After Global Myocardial Ischemia

BACKGROUND Although Toll-like receptor 4 (TLR4) has been implicated in the myocardial injury caused by regional ischemia/reperfusion, its role in the myocardial inflammatory response and in contractile dysfunction after global ischemia/reperfusion is unclear. Cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), contribute to the mechanism of myocardial dysfunction after global ischemia/reperfusion. We hypothesized that a TLR4-mediated cytokine cascade modulates myocardial contractile function after global ischemia/reperfusion. This study examined whether TLR4 regulates TNF-alpha and interleukin (IL)-1beta peptide production during global ischemia/reperfusion and whether TLR4 signaling influences postischemic cardiac function through TNF-alpha and IL-1beta. METHODS Isolated hearts from wild-type mice, two strains of TLR4 mutants, TNF-alpha knockouts, and IL-1beta knockouts underwent global ischemia/reperfusion. Cardiac contractile function was analyzed, and myocardial nuclear factor-kappaB activity and TNF-alpha and IL-1beta levels were measured. RESULTS In wild-type hearts, global ischemia/reperfusion induced nuclear factor-kappaB activation and the production of TNF-alpha and IL-1beta peptides. In TLR4-mutant hearts, these changes were significantly reduced and postischemic functional recovery was improved. Application of TNF-alpha and IL-1beta to TLR4-mutant hearts abrogated this improvement in postischemic functional recovery. Postischemic functional recovery also improved in TNF-alpha knockout and IL-1beta knockout hearts, as well as in wild-type hearts treated with TNF-binding protein or IL-1 receptor antagonist. CONCLUSIONS This study demonstrates that TLR4 signaling contributes to cardiac dysfunction after global ischemia/reperfusion. TLR4 signaling mediates the production of TNF-alpha and IL-1beta peptides, and these two cytokines link TLR4 signaling to postischemic cardiac dysfunction.

Implementation of an acute care surgery service at an academic trauma center.

BACKGROUND The establishment of acute care surgery is rapidly becoming a solution to meet emergency surgical needs. Challenges include competition for emergency surgery opportunities and the ability to economically sustain a practice. METHODS Clinical activity was measured by reviewing the institutional and practice plan databases. Work relative value units and practice plan collection rates defined clinical activity and revenue. RESULTS Operative procedures and intensive care unit activity accounted for 52% and 36% of activity, respectively. Although procedures on the digestive tract accounted for half of the operative activity, significant activity was observed in nearly all other systems. Overall clinical productivity remained constant but did demonstrate a 25% increase in operative work relative value units. Current billing activity supports 4.0 clinical full-time equivalents, but estimated collections would cover <73% of physician direct costs. CONCLUSIONS The authors describe the implementation of an acute care surgery service that combines trauma, emergency general surgery, and surgical critical care in an established academic surgery department. Developing a sustainable economic model must include income sources other than patient service revenue.

Fifteen-year trauma system performance analysis demonstrates optimal coverage for most severely injured patients and identifies a vulnerable population.

BACKGROUND Trauma systems are designed to deliver timely and appropriate care. Prehospital triage regulations and interfacility transfer guidelines are the primary determinants of system efficacy. We analyzed the effectiveness of the Florida trauma system in delivering trauma patients to trauma centers over time. STUDY DESIGN Injured patients were identified by ICD-9 codes from a statewide discharge dataset, and they were categorized as children (less than 16 years old), adult (16 to 65 years old), or elderly (over 65 years old). Severe injury was defined by International Classification Injury Severity Scores (ICISS) < 0.85. Residence ZIP codes were used as a surrogate for injury location. RESULTS Severe injury discharges increased at designated trauma centers (DTCs) and decreased at nontrauma centers (NTCs). The proportion of patients with severe injuries discharged from DTCs increased for all age groups, capturing nearly all severely injured children and adults. Access to DTCs was dependent on proximity for severely injured elderly but not for severely injured children and adults. CONCLUSIONS Triage improved over time, enabling near complete capture of at-risk children and adults independent of DTC proximity. Because distance from a DTC does not limit access for children and adults, existing trauma system resources are sufficient to meet the current demands. Efforts are needed to determine the trauma resource and triage needs of the severely injured elderly.

Diagnostic peritoneal lavage remains a valuable adjunct to modern imaging techniques.

BACKGROUND Continuing improvements in computerized tomography scan technology and widespread acceptance of focused abdominal sonography for trauma (FAST) have prompted the suggestion that diagnostic peritoneal lavage (DPL) is obsolete. This sentiment, coupled with decreasing resident familiarity with DPL, has led to a poor understanding of the modern indications for DPL and no clear guidelines. We hypothesized that, while its indications may have changed, DPL remains essential in the rapid, effective triage of the trauma patient. METHODS We queried our Level I trauma centers trauma registry from January 1996 through August 2006 for patients who underwent a DPL as part of their initial evaluation. Specific variables investigated were indications for or results of DPL, performance of a laparotomy in the first 24 hours, and operative findings. RESULTS Six hundred twenty-seven patients underwent DPL (145 positive, 482 negative). Although the accuracy of DPL for predicting therapeutic laparotomy for all patients was only 77%, in the subset of hemodynamically unstable patients (of which only 46% had a positive FAST), it was 100%. Conversely, only 7% of all patients with negative DPL subsequently had a therapeutic laparotomy, with only 5% in the subset of stab wounds. CONCLUSION DPL continues to be a vital tool in the evaluation of the trauma patient. A positive test in the hemodynamically unstable patient with potential multisystem trauma allows for expeditious intervention. A negative test in abdominal stab wounds supports observation and early subsequent discharge. Our current guidelines continue to emphasize the complimentary roles of DPL, FAST, and computerized tomography scan in the trauma bay.

Geographic distribution of severely injured patients: implications for trauma system development.

BACKGROUND Despite decades of trauma system development, many severely injured patients fail to reach a trauma center for definitive care. The purpose of this study was to define the regions served by Florida’s designated trauma centers and define the geographic distribution of severely injured patients who do not access the state’s trauma system. METHODS Severely injured patients discharged from Florida hospitals were identified using the 2009 Florida Agency for Health Care Administration database. The home zip codes of patients discharged from trauma and nontrauma center hospitals were used as a surrogate for injury location and plotted on a map. A radial distance containing 75% of trauma center discharges defined trauma center catchment area. RESULTS Only 52% of severely injured patients were discharged from trauma centers. The catchment areas varied from 204 square miles to 12,682 square miles and together encompassed 92% state’s area. Although 93% of patients lived within a trauma center catchment area, the proportion treated at a trauma center in each catchment area varied from 13% to 58%. Mapping of patient residences identified regions of limited access to the trauma system despite proximity to trauma centers. CONCLUSIONS The distribution of severely injured patients who do not reach trauma centers presents an opportunity for trauma system improvement. Those in proximity to trauma centers may benefit from improved and secondary triage guidelines and interfacility transfer agreements, whereas those distant from trauma centers may suggest a need for additional trauma system resources. LEVEL OF EVIDENCE Epidemiologic study, level III.

The injured elderly: a rising tide.

BACKGROUND Injury remains a public health challenge despite advances in trauma care. Periodic survey of injury epidemiology is essential to the trauma systems continuous performance improvement. We undertook this study to characterize the changes in Florida injury rates during the past 15 years. METHODS Injured patients were identified with the use of a statewide database over 15 years ending in 2010. Population data were obtained from the U.S. Census. Severe injury was defined by International Classification Injury Severity Scores less than 0.85. Injury rates were expressed in discharges per 100,000 residents. Trends were analyzed by linear regression. RESULTS The 1.5 million patient discharges consisted of 5.2% children, 39.7% adults, and 55.1% elderly. The overall injury rate decreased in children by 18% but increased in adults by 2% and in the elderly by 17% during the study period. The proportion of severe injuries decreased in children and the elderly but did not change in adults. Injury patterns changed in all age groups. CONCLUSION Injury in the elderly is increasing at a rate seven times that of adults. In 2010, the elderly accounted for only 17% of the population but 55% of injury-related discharges. These trends have dramatic implications for the design of future trauma systems and health care resource use.

Measuring trauma system performance: Right patient, right place - Mission accomplished?

BACKGROUND A regional trauma system must establish and monitor acceptable overtriage and undertriage rates. Although diagnoses from discharge data sets can be used with mortality prediction models to define high-risk injury, retrospective analyses introduce methodological errors when evaluating real-time triage processes. The purpose of this study was to determine if major trauma patients identified using field criteria correlated with those retrospectively labeled high risk and to assess system performance by measuring triage accuracy and trauma center utilization. METHODS A statewide database was queried for all injury-related International Classification of Diseases, 9th Revision, code discharges from designated trauma centers and nontrauma centers for 2012. Children and burn patients were excluded. Patients assigned a trauma alert fee were considered field-triage(+). The International Classification Injury Severity Score methodology was used to estimate injury-related survival probabilities, with an International Classification Injury Severity Score less than 0.85 considered high risk. Triage rates were expressed relative to the total population; the proportion of low- and high-risk patients discharged from trauma centers defined trauma center utilization. RESULTS There were 116,990 patients who met study criteria, including 11,368 (10%) high-risk, 70,741 field-triage(−) patients treated in nontrauma centers and 28,548 field-triage(−) and 17,791 field-triage(+) patients treated in trauma centers. Field triage was 86% accurate, with 10% overtriage and 4% undertriage. System triage was 66% accurate, with 32% overtriage and 2% undertriage. Overtriage patients more often, and undertriage patients less often, had severe injury characteristics than appropriately triaged patients. CONCLUSION Trauma system performance assessed using retrospective administrative data provides a convenient measure of performance but must be used with caution. Residual mistriage can partly be attributed to error introduced by retrospective high-risk definitions, whereas differences between field and system triage accuracy can be attributed to the trauma center’s role as a large community hospital. Given the limitations of the data and methods, these results may represent optimal patient distribution within this mature system.