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BACKGROUND A 2015 American Association for the Surgery of Trauma trial reported a 32% mortality for pelvic fracture patients in shock. Angioembolization (AE) is the most common intervention; the Maryland group revealed time to AE averaged 5 hours. The goal of this study was to evaluate the time to intervention and outcomes of an alternative approach for pelvic hemorrhage. We hypothesized that preperitoneal pelvic packing (PPP) results in a shorter time to intervention and lower mortality. METHODS In 2004, we initiated a PPP protocol for pelvic fracture hemorrhage. RESULTS During the 11-year study, 2,293 patients were admitted with pelvic fractures; 128 (6%) patients underwent PPP (mean age, 44 ± 2 years; Injury Severity Score (ISS), 48 ± 1.2). The lowest emergency department systolic blood pressure was 74 mm Hg and highest heart rate was 120. Median time to operation was 44 minutes and 3 additional operations were performed in 109 (85%) patients. Median RBC transfusions before SICU admission compared with the 24 postoperative hours were 8 versus 3 units (p < 0.05). After PPP, 16 (13%) patients underwent AE with a documented arterial blush.Mortality in this high-risk group was 21%. Death was due to brain injury (9), multiple organ failure (4), pulmonary or cardiac failure (6), withdrawal of support (4), adverse physiology (3), and Mucor infection (1). Of those patients with physiologic exhaustion, 2 died in the operating room at 89 and 100 minutes after arrival, whereas 1 died 9 hours after arrival. CONCLUSIONS PPP results in a shorter time to intervention and lower mortality compared with modern series using AE. Examining mortality, only 3 (2%) deaths were attributed to the immediate sequelae of bleeding with physiologic failure. With time to death under 100 minutes in 2 patients, AE is unlikely to have been feasible. PPP should be used for pelvic fracture-related bleeding in the patient who remains unstable despite initial transfusion. LEVEL OF EVIDENCE Therapeutic study, level IV.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2–5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8–18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2–5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory., Highlights • Studied differences in regional volume change longitudinally between TBI and control. • Found decreases in TBI group in white matter, gray matter and subcortical regions • Changes in regional volume were associated with changes in cognitive performance. • Compared subgroups within TBI group based on interhemispheric transfer time (IHTT) • TBI-slow group seems to drive TBI vs. control results, show prolonged degeneration.

Background We implemented expanded screening criteria for blunt cerebrovascular injuries (BCVIs) in an attempt to capture the remaining 20% of patients not historically identified with earlier protocols. We hypothesized that these expanded criteria would capture the additional 20% of BCVI patients not previously identified. Methods Screening criteria for BCVI were expanded in 2011 after identifying new injury patterns. The study population included 4 years prior (2007 to 2010; classic) and following (2011 to 2014; expanded) implementation of expanded criteria. Results BCVIs were identified in 386 patients: 150 during the classic period (2.36% incidence) and 236 in the expanded period (2.99% incidence). In the expanded period, 155 patients were imaged based on classic screening criteria, 62 on expanded criteria (21 complex skull fractures, 20 upper rib fractures, 6 mandible fractures, 2 scalp degloving, 1 great vessel injury, and 12 combination), and 19 for other injuries and symptoms. Conclusions There was a significant increase in the identification of BCVI following the adoption of expanded screening criteria, resulting in a substantial reduction of missed injuries. Expanded criteria should be adopted when screening for BCVI.

Annually, more than 2 million patients are admitted with emergency general surgery (EGS) conditions. Emergency general surgery cases comprise 11% of all general surgery operations, yet account for 47% of mortalities and 28% of complications. Using the statewide general surgery Michigan Surgical Quality Collaborative (MSQC) data, we previously confirmed that wide variations in EGS outcomes were unrelated to case volume/complexity. We assessed whether patient care model (PCM) affected EGS outcomes.There were 34 hospitals that provided data for PCM, resources, surgeon practice patterns, and comprehensive MSQC patient data from January 1, 2008 to December 31, 2016 (general surgery cases = 126,494; EGS cases = 39,023). Risk and reliability adjusted outcomes were determined using hierarchical multivariable logistic regression analysis with multiple clinical covariates and PCM.The general surgery service (GSS) model was more common (73%) than acute care surgery (ACS, 27%). Emergency general surgery 30-day mortality was 4.1% (intestinal resections 11.6%). The ACS model was associated with a reduction of 31% in mortality (odds ratio [OR] 0.69; 95% CI 0.52-0.92] for EGS cases, related to decreased mortality in the intestinal resection cohort (8.5% ACS vs 12% GSS, p0.0001). Morbidity in EGS was 17.4% (9.7% elective); highest (40%) in intestinal resection, and PCM did not affect morbidity. We identified specific variables for an optimal EGS risk adjustment model.This is the first multi-institutional study to identify that an ACS model is associated with a significant 31% mortality reduction in EGS using prospectively collected, clinically obtained, research-quality collaborative data. We identified that new risk adjustment models are necessary for EGS outcomes evaluations.

Background This phase II CALGB trial evaluated the activity and safety of an extended induction schedule of galiximab (G) plus rituximab (R) in untreated follicular lymphoma (FL). Patients and methods Patients with previously untreated FL (grades 1, 2, 3a) received 4 weekly infusions of G + R, followed by an additional dose every 2 months four times. International Workshop Response Criteria were used to evaluate response. Results Sixty-one patients were treated and antibody infusions were well tolerated. The overall response rate (ORR) is 72.1% (95% confidence interval 59.2% to 82.9%): 47.6% complete response (CR)/unconfirmed complete response (CRu) and 24.6% partial response. At a median follow-up time of 4.3 years (range, 0.3–5.3 years) median progression-free survival (PFS) is 2.9 years. Notably, Follicular Lymphoma International Prognostic Index (FLIPI) correlated with ORR, CR rate, and PFS, and the low-risk FLIPI group (n = 12) achieved a 92% ORR, 75% CR/CRu rate, and 75% 3-year PFS. Conclusions An extended induction schedule of G + R in previously untreated FL is well tolerated and appears particularly efficacious in those patients with low-risk FLIPI scores. In addition, this trial served as the initial platform for additional CALGB ‘doublet’ combination regimes of rituximab plus other novel targeted agents.

Purpose Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies. Patients and Methods The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m2 weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk. Results Ninety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023). Conclusion LR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.

Author(s): Pieracci, Fredric M; Johnson, Jeffrey L; Stovall, Robert T; Jurkovich, Gregory J

Refinement of criteria for both screening and initiation of empiric therapy in ventilator-associated pneumonia (VAP) will minimize antibiotic overuse. We hypothesized that variables within the commonly used Clinical Pulmonary Infection Score (CPIS) have unfavorable test performance characteristics.Consecutive bronchoalveolar lavage (BAL) cultures obtained from surgical intensive care unit patients were abstracted (2009-2012). Ventilator-associated pneumonia was defined as ≥10(5) cfu/mL. The CPIS both without (CPISclinical) and with (CPISclinical+GS) the result of gram stain (GS) was calculated. Test performance characteristics for the sample, as well as several subgroups, were compared.One thousand thirteen lower respiratory tract cultures from 492 patients were analyzed; 438 (43.2%) of cultures were classified as VAP, and 310 of 492 patients (62.4%) had ≥1 episode of VAP. Both CPISclinical and CPISclinical+GS had poor discrimination for VAP (Receiver-operating characteristic area under the curve=0.55 and 0.66, respectively). Sensitivity of CPISclinical using a threshold of6 was 21%; the lowest threshold for CPISclinical for which the sensitivity was at least 85% was 3. The highest sensitivity among the individual CPIS components was new CXR infiltrate (91.1%). Among the subset of cultures sent during the early VAP window (days intubated 2-5), organisms on GS had a sensitivity of 93.3%. The CPISclinical, CPISclinical+GS, organisms, and neutrophils on GS parameters all became less accurate in both the late VAP window and when screening for recurrent VAP. Every case of VAP had at least one of the following: 1) fever; 2) new CXR infiltrate, or 3) organisms on GS.In this series of BALs, traditional screening tools for VAP missed the majority of microbiological confirmed cases. Screening based on either new CXR infiltrate or fever yielded an acceptably high sensitivity. The only scenario identified in which empiric antibiotics could be withheld safely was the absence of organisms on GS in the early VAP window.

BACKGROUND: Older patients with traumatic brain injury (TBI) may be at high risk of death after hospitalization. The purpose of this study was to characterize long-term mortality of older TBI patients who survived to discharge. We hypothesized that predictors of postdischarge mortality differed from those of inpatient mortality. METHODS: A retrospective cohort study was performed on TBI patients older than 55 years admitted to our Level I trauma center between July 1, 2006, and December 31, 2011. Postdischarge deaths were identified by matching patient data with local vital records up to December 31, 2011, when data collection was terminated (censoring). Patients were categorized by age, comorbidities, history of preinjury anticoagulant/prescription antiplatelet agent therapy, injury severity indices, initial TBI type, prehospital living status, discharge location, and discharge condition. The effect of risk factors on postdischarge mortality was evaluated by Cox proportional hazards modeling. RESULTS: Of 353 patients, 322 (91.2%) survived to discharge. Postdischarge mortality was 19.8% (n = 63) for the study period. Of the postdischarge deaths, 54.0% died within 6 months of discharge, and 68.3% died within 1 year. Median days to death after discharge or censoring were 149 and 410, respectively. Factors associated with death after discharge included age, preinjury anticoagulant use, higher number of Charlson comorbidities, discharge to a long-term care facility, and severe disability. Factors related to injury severity (i.e., Injury Severity Score [ISS], initial Glasgow Coma Scale [GCS] score) and preinjury prescription antiplatelet agent use, previously found to predict inpatient death, did not predict postdischarge mortality. CONCLUSION: Older TBI patients who survive to discharge have a significant risk of death within 1 year. Predictors of postdischarge mortality and inpatient death differ. Death after discharge is largely a function of overall health status. Monitoring health status and continued aggressive management of comorbidities after discharge may be essential in determining long-term outcomes. LEVEL OF EVIDENCE: Epidemiologic/retrospective cohort analysis, level III. Language: en

BACKGROUND: The diagnosis of blunt abdominal trauma can be challenging and resource intensive. Observation with serial clinical assessments plays a major role in the evaluation of these patients, but the time required for intra-abdominal injury to become clinically apparent is unknown. The purpose of this study was to determine the amount of time required for an intra-abdominal injury to become clinically apparent after blunt abdominal trauma via physical examination or commonly followed clinical values. METHODS: A retrospective review of patients who sustained blunt trauma resulting in intra-abdominal injury between June 2010 and June 2012 at a Level 1 academic trauma center was performed. Patient demographics, injuries, and the amount of time from emergency department admission to sign or symptom development and subsequent diagnosis were recorded. All diagnoses were made by computed tomography or at the time of surgery. Patient transfers from other hospitals were excluded. RESULTS: Of 3,574 blunt trauma patients admitted to the hospital, 285 (8%) experienced intra-abdominal injuries. The mean (SD) age was 36 (17) years, the majority were male (194 patients, 68%) and the mean (SD) Injury Severity Score (ISS) was 21 (14). The mean (SD) time from admission to diagnosis via computed tomography or surgery was 74 (55) minutes. Eighty patients (28%) required either surgery (78 patients, 17%) or radiographic embolization (2 patients, 0.7%) for their injury. All patients who required intervention demonstrated a sign or symptom of their intra-abdominal injury within 60 minutes of arrival, although two patients were intervened upon in a delayed fashion. All patients with a blunt intra-abdominal injury manifested a clinical sign or symptom of their intra-abdominal injury, resulting in their diagnosis within 8 hours 25 minutes of arrival to the hospital. CONCLUSION: All diagnosed intra-abdominal injuries from blunt trauma manifested clinical signs or symptoms that could prompt imaging or intervention, leading to their diagnosis within 8 hours 25 minutes of arrival to the hospital. All patients who required an intervention for their injury manifested a sign or symptom of their injury within 60 minutes of arrival. (J Trauma Acute Care Surg. 2014;76:1020Y1023. Copyright * 2014 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Therapeutic study, level IV. Epidemiologic study, level III.

While the incidence of postinjury multiple-organ failure (MOF) has declined during the past decade, temporal trends of its morbidity, mortality, presentation patterns, and health care resources use have been inconsistent. The purpose of this study was to describe the evolving epidemiology of postinjury MOF from 2003 to 2010 in multiple trauma centers sharing standard treatment protocols."Inflammation and Host Response to Injury Collaborative Program" institutions that enrolled more than 20 eligible patients per biennial during the 2003 to 2010 study period were included. The patients were aged 16 years to 90 years, sustained blunt torso trauma with hemorrhagic shock (systolic blood pressure90 mm Hg, base deficit ≥ 6 mEq/L, blood transfusion within the first 12 hours), but without severe head injury (motor Glasgow Coma Scale [GCS] score4). MOF temporal trends (Denver MOF score3) were adjusted for admission risk factors (age, sex, body max index, Injury Severity Score [ISS], systolic blood pressure, and base deficit) using survival analysis.A total of 1,643 patients from four institutions were evaluated. MOF incidence decreased over time (from 17% in 2003-2004 to 9.8% in 2009-2010). MOF-related death rate (33% in 2003-2004 to 36% in 2009-2010), intensive care unit stay, and mechanical ventilation duration did not change over the study period. Adjustment for admission risk factors confirmed the crude trends. MOF patients required much longer ventilation and intensive care unit stay, compared with non-MOF patients. Most of the MOF-related deaths occurred within 2 days of the MOF diagnosis. Lung and cardiac dysfunctions became less frequent (57.6% to 50.8%, 20.9% to 12.5%, respectively), but kidney and liver failure rates did not change (10.1% to 12.5%, 15.2% to 14.1%).Postinjury MOF remains a resource-intensive, morbid, and lethal condition. Lung injury is an enduring challenge and should be a research priority. The lack of outcome improvements suggests that reversing MOF is difficult and prevention is still the best strategy.Epidemiologic study, level III.

To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19-79 years) were enrolled; 27% were >60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (one central nervous system bleed, four infections, two respiratory failure); five were >60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions.

IntroductionRib fractures in elderly patients are associated with increased morbidity and mortality. Predicting which patients are at risk for complications is an area of debate. Current models use anatomic, physiologic or laboratory parameters in isolation to answer this question. The ‘RibScore’ is an anatomic model that assesses fracture severity. Given that frailty is a major driver of adverse outcomes in the elderly, we hypothesize that the combined analysis of fracture severity, physiologic reserve and current pulmonary function are better predictors of respiratory compromise in this population.MethodsThis is a retrospective chart review of 263 trauma patients age ≥55 from January 2014 to June 2017. Criteria included blunt mechanism and ≥ 1 rib fracture identified by CT. Variables indicating adverse pulmonary outcomes were defined by: pneumonia, respiratory failure and tracheostomy. Three models were assessed: (1) RibScore, (2) Modified Frailty Index (mFI) and (3) initial partial pressure of carbondioxide (PaCO2).ResultsA total of 263 patients met inclusion criteria. 13% developed pulmonary complications. Increased RibScore, mFI and PaCO2 were each statistically associated with risk of complications. Receiver operating characteristics area under the curve analysis of individual models predicted complications with the following concordance statistic (CS): anatomic (RibScore) yielded a CS of 0.79 (95% CI 0.69 to 0.89); physiologic (mFI) yielded a CS of 0.83 (95% CI 0.75 to 0.91) and laboratory (PaCO2) yielded a CS of 0.88 (95% CI 0.80 to 0.95). The PaCO2 had the highest discriminative ability of the three individual models. Combining all three models yielded the best performance with a CS of 0.90 (95% CI 0.81 to 0.97).DiscussionThe RibScore maintains discriminative ability in the elderly. However, models based on mFI and PaCO2 individually outperform the RibScore. A combination of all three models yields the highest discriminative ability. This combined approach is best for assessing the severity of rib fractures and prediction of complications in the elderly.Level of evidencePrognostic Study, Level III.

Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.

Background Urinary tract infection (UTI) in trauma patients is associated with increased mortality. Whether the urinalysis (UA) is an adequate test for a urinary source of fever in the ICU trauma patient has not been demonstrated. We hypothesized that the UA is a valuable screen for UTI in the febrile, critically ill trauma patient. Study Design All trauma ICU patients in our surgical ICU who had a fever (temperature >38.0°C), urinary catheter, UA, and a urine culture between January 1, 2011 and December 13, 2011 were reviewed. A positive UA was defined as positive leukocyte esterase, positive nitrite, WBC > 10/high power field, or presence of bacteria. A positive urine culture was defined as growth of ≥10 5 colony forming units (cfu) of an organism irrespective of the UA result or ≥10 3 cfu in the setting of a positive UA. A UTI was defined as positive urine culture without an alternative cause of the fever. Results There were 232 UAs from 112 patients that met criteria. The majority (75%) of patients were men; the mean age was 40 (±16) years. Of the 232 UAs, 90 (38.7%) were positive. There were 14 UTIs. The sensitivity, specificity, positive predictive value, and negative predictive value of the UA for UTI were 100%, 65.1%, 15.5%, and 100%, respectively. Conclusions A negative UA reliably excludes a catheter-associated UTI in the febrile, trauma ICU patient with a 100% negative predictive value, and it can rapidly direct the clinician toward more likely sources of fever and reduce unnecessary urine cultures.

BACKGROUND Rhabdomyolysis following trauma has been associated with renal impairment. Nevertheless, the literature is scant in risk assessment of acute kidney injury (AKI) and survival in children experiencing posttraumatic rhabdomyolysis. METHODS After institutional review board approval was obtained, the registry of an urban trauma center was reviewed for pediatric (age < 18 years) trauma admissions with available creatine kinase (CK) values. Variables extracted included demographics and trauma severity indices along with serum creatine, CK, and Blood Urea Nitrogen (BUN) values. AKI was defined per pediatric RIFLE (Risk, Injury, Failure, Loss, End stage) definition. Regression models were deployed to determine the independent risk factors for AKI and CK levels. RESULTS Overall, 521 patients constituted the study sample. AKI occurred in 70 patients (13.4%), with correlation to CK values in excess of 3,000 IU/L (41.4% vs. 4.9%, adjusted p < 0.001). Independent risk factors for AKI proved to be CK level of 3,000 or greater (adjusted odds ratio [AOR], 11.02; 95% confidence interval [CI], 4.56-26.64; p < 0.001), Injury Severity Score (ISS) of 15 or less (AOR, 0.25; 95% CI, 0.10-0.61), Glasgow Coma Scale (GCS) score of 8 or less (AOR, 15.00; 95% CI, 4.98-44.94), abdominal Abbreviated Injury Scale (AIS) score of 3 or less (AOR, 3.14; 95% CI, 1.04-5.36), imaging studies with contrast of 3 or less (AOR, 3.81; 95% CI, 1.37-10.57), blunt mechanism of injury (AOR, 2.76; 95% CI, 1.17-6.49), administration of nephrotoxic agents (AOR, 4.81; 95% CI, 1.23-18.79), and requirement for fluids administration in the emergency department (AOR, 2.36; 95% CI, 1.04-5.36). Mortality in the study sample with CK values of 3,000 or greater versus less than 3,000 IU/L did not reach statistical significance (25.0% vs. 9.3%, adjusted p = 0.787). CONCLUSION AKI in pediatric posttraumatic rhabdomyolysis occurs in 13% of trauma patients. CK values of 3,000 IU/L or greater pose a significant adjusted risk for AKI. Aggressive monitoring of CK values in pediatric trauma patients is warranted. LEVEL OF EVIDENCE Prognostic study, level III.

BACKGROUND: In contrast to the established principles of ‘‘damage-control orthopedics’’ for temporary external fixation of long bone or pelvic fractures, the ‘‘ideal’’ timing and modality of fixation of unstable spine fractures in severely injured patients remains controversial. METHODS: A prospective cohort study was designed to evaluate the safety and efficacy of a standardized ‘‘spine damage-control’’ (SDC) protocol for the acute management of unstable thoracic and lumbar spine fractures in severely injured patients. A total of 112 consecutive patients with unstable thoracic or lumbar spine fractures and Injury Severity Score (ISS) of greater than 15 were prospectively enrolled in this study from October 1, 2008, to December 31, 2011. Acute posterior spinal fixation within 24 hours was performed in 42 patients (SDC group), and 70 patients underwent definitive operative spine fixation in a delayed fashion (‘‘delayed surgery’’[DS] group). Both cohorts were prospectively analyzed for baseline demographics, length of operative time, amount of intraoperative blood loss, total hospital length of stay, number of ventilator-dependent days, and incidence of early postoperative complications. RESULTS: The mean time to initial spine fixation was significantly decreased in the SDC group (8.9 [1.7] hours vs. 98.7 [22.4] hours, p G 0.01). The SDC cohort had a reduced mean length of operative time (2.4 [0.7] hours vs. 3.9 [1.3] hours), length of hospital stay (14.1 [2.9] days vs. 32.6 [7.8] days), and number of ventilator-dependent days (2.2 [1.5] days vs. 9.1 [2.4] days), compared with the DS group (p G 0.05). Furthermore, the complication rate was decreased in the SDC group with regard to wound complications (2.4% vs. 7.1%), urinary tract infections (4.8% vs. 21.4%), pulmonary complications (14.3% vs. 25.7%), and pressure sores (2.4% vs. 8.6%), compared with the DS cohort (p G 0.05). CONCLUSION: A standardized SDC protocol represents a safe and efficient treatment strategy for severely injured patients with associated unstable thoracic or lumbar fractures. (J Trauma Acute Care Surg. 2013;74: 590Y596. Copyright* 2013 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Therapeutic study, level III.

Analogous to organ injury scales developed for trauma, a scoring system is needed for acute care surgery. The purpose of this study was to develop a disease severity score (DSS) for acute appendicitis, the most common surgical emergency.A panel of acute care surgery experts reviewed the literature and developed a DSS for acute appendicitis as follows: grade 1, inflamed; Grade 2, gangrenous; Grade 3, perforated with localized free fluid; Grade 4, perforated with a regional abscess; and Grade 5, perforated with diffuse peritonitis. We applied the DSS to 1,000 consecutive patients undergoing appendectomy from 1999 to 2009 and examined its association with outcomes (mortality, length of hospital stay, incidence of in-hospital, and postdischarge complications). Of the 1,000 patients, 82 were excluded owing to negative or interval appendectomy or advanced end-stage renal disease.Among 918 eligible patients, the DSS distribution was Grade 1 at 62.4%, Grade 2 at 13.0%, Grade 3 at 18.7%, Grade 4 at 4.4%, and Grade 5 at 1.5%. Statistical analyses indicated a stepwise risk increase in adverse outcomes with higher DSS grades (c statistics ≥ 0.75 for all outcomes). Covariates (age, sex, and type of surgical access) did not add to the predictive power of DSS.Based on this single-institution study, the proposed appendicitis DSS seems to be a useful tool. This DSS can inform future, national efforts, which can build on the knowledge provided by the present investigation. This DSS may be useful for comparing therapeutic modalities, planning resource use, improving programs, and adjusting reimbursementEpidemiologic study, level III.

Background Chest CT is more sensitive than a chest X-ray (CXR) in diagnosing rib fractures; however, the clinical significance of these fractures remains unclear. Objectives The purpose of this study was to determine the added diagnostic use of chest CT performed after CXR in patients with either known or suspected rib fractures secondary to blunt trauma. Methods Retrospective cohort study of blunt trauma patients with rib fractures at a level I trauma center that had both a CXR and a CT chest. The CT finding of ≥ 3 additional fractures in patients with ≤ 3 rib fractures on CXR was considered clinically meaningful. Student’s t-test and chi-square analysis were used for comparison. Results We identified 499 patients with rib fractures: 93 (18.6%) had CXR only, 7 (1.4%) had chest CT only, and 399 (79.9%) had both CXR and chest CT. Among these 399 patients, a total of 1,969 rib fractures were identified: 1,467 (74.5%) were missed by CXR. The median number of additional fractures identified by CT was 3 (range, 4 - 15). Of 212 (53.1%) patients with a clinically meaningful increase in the number of fractures, 68 patients underwent one or more clinical interventions: 36 SICU admissions, 20 pain catheter placements, 23 epidural placements, and 3 SSRF. Additionally, 70 patients had a chest tube placed for retained hemothorax or occult pneumothorax. Overall, 138 patients (34.5%) had a change in clinical management based upon CT chest. Conclusions The chest X-ray missed ~75% of rib fractures seen on chest CT. Although patients with a clinical meaningful increase in the number of rib fractures were more likely to be admitted to the intensive care unit, there was no associated improvement in pulmonary outcomes.

Summary Background We report the long-term outcome analysis of 12 patients who underwent two-stage abdominal wall reconstruction using combined submuscular tissue expansion and anterior components separation (CS) technique. Methods Outcome measures were (1) the patients were assessed for the presence or absence of recurrence; (2) patient-reported outcomes on physical functioning in relation with the abdominal wall reconstruction were evaluated using the SF 36-item health survey. Results The mean age, average expansion volume, and mean time expansion were 37.5 years, 1250 cc, and 9.5 weeks, respectively. The average soft tissue deficiency size was 15.5 (width) × 19.5 (length) cm 2 . The average fascial defect was 17 (width) × 21.5 (length) cm 2 . No mesh-assisted technique was required. Primary closure was obtained in all. The average follow-up was 39.6 months. Hernia recurrence was noted in one patient (8.3%). All 12 patients completed the SF 36-item health survey. Moreover, 75% of the patients reported 100%, indicating "Not limited in vigorous activities," and 25% indicated "limited a little." All patients reported 100% "not limited at all" in lifting or carrying groceries, climbing several flights of stairs, climbing one flight of stairs, bending, kneeling, stooping, walking more than a mile, walking several blocks, walking one block, bathing, or dressing. Conclusions Parietal laxity obtained with tissue expansion increases the possibility of direct closure of the fascial layer, skin, and subcutaneous tissue components. Combined use of tissue expansion and CS may result in favorable long-term outcomes as evidenced by patient-reported physical functioning data and low rate of hernia recurrence.

Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA).This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival.One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2-11), TEG: 4.5 (2-8)] (P = 0.317), but more plasma units [CCA: 2.0 (0-4), TEG: 0.0 (0-3)] (P = 0.022), and more platelets units [CCA: 0.0 (0-1), TEG: 0.0 (0-0)] (P = 0.041) in the first 2 hours of resuscitation.Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.

BACKGROUND: Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis. METHODS: One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years. RESULTS: One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged

Despite improved resuscitation strategies, acute kidney injury (AKI) remains an important cause of morbidity and high resource use among severely injured patients. Thus, we conducted a comprehensive evaluation of the epidemiology and outcomes of early AKI among severely injured patients as well as its impact on the development of postinjury multiple organ failure (MOF).We queried our 17-year database of high-risk postinjury patients (Injury Severity Score15, age15 years, survival48 hours, and no isolated head injury). MOF and AKI (creatinine1.8 mg/dL) were defined by the Denver MOF score. Patients with documented preexisting renal, hepatic, cardiac, or pulmonary disease (120, 5%) were excluded, leaving 2157 for analysis.Early (day 2) AKI was evident in 2.13% of the patients and associated with a 78% MOF incidence and 27% mortality. Both rates were higher than those associated with early heart, lung, or liver failure.Early AKI is a harbinger of adverse outcome postinjury, outperforming hepatic, cardiac, or pulmonary dysfunction as a predictor of MOF and death. Prevention of early AKI and a better understanding of organ crosstalk may help reduce AKI-associated morbidity, mortality, and obligatory costs of this complication.I, prognostic study.

Background Recent data indicate comparable efficacy and safety for levetiracetam (LEV) when compared with phenytoin (PHT) for prophylaxis of early seizures after traumatic brain injury. The purpose of this study was to conduct a cost-minimization analysis, from the perspective of both the acute care institution (cost) and patient (charges), comparing these two strategies. Methods A decision tree was constructed to include baseline event probabilities obtained from detailed literature review, costs, and charges. Monte Carlo simulation was used to derive the mean costs and charges per patient treated with the LEV when compared with the PHT strategy. Adverse event probabilities, costs, charges, and frequency of laboratory determination for the PHT group were varied in sensitivity analyses. Results Literature review indicated equal efficacy of PHT versus LEV for early seizure prevention. The PHT strategy was superior to the LEV strategy from both the institutional (mean cost per patient $151.24 vs. $411.85, respectively) and patient (mean charge per patient $2,302.58 vs. $3,498.40, respectively) perspectives. Varying both baseline adverse event probabilities and frequency of laboratory testing did not alter the superiority of the PHT strategy. LEV replaced PHT as the dominant strategy only when the cost/charge of treating mental status deterioration was increased markedly above baseline. Conclusions From both institutional and patient perspectives, PHT is less expensive than LEV for routine pharmacoprophylaxis of early seizures among traumatic brain injury patients. Pending compelling efficacy data, LEV should not replace PHT as a first-line agent for this indication.

Background Multiple techniques have been introduced to obtain fascial closure for the open abdomen. Vacuum-assisted closure has reduced but not eliminated the use of either split-thickness skin grafts to cover the exposed bowel or mesh (prosthetic or biological) approximation of the fascia. We hypothesized that a sequential closure technique performed by a systematic protocol would achieve a higher rate of primary fascial closure than other described techniques. Methods Our technique of sequential fascial closure was initiated in 2005. Patients with a postinjury open abdomen undergoing the technique were compared with those patients who did not follow the protocol. In brief, vacuum-assisted closure white sponges cover the bowel; the fascia is placed under moderate tension over the white sponges with no. 1-polydioxanone sutures; the black sponge is placed on top of this with the standard occlusive dressing; patients undergo partial fascial closure and replacement of the sponge sandwich every 2 days until completely closed. Protocol violations were defined as not returning to the operating room every other day and absence of fascial retention sutures. Patients who died before return to the operating room in the first 48 hours were excluded. Results One hundred consecutive patients underwent damage control surgery during the five-year study period and survived to second laparotomy; 49 patients attained fascial closure at the second laparotomy. Fifty-one patients required an open abdomen after the second laparotomy and comprise the study population. The majority were men (80%) with a mean age of 34.7 years ± 2.0 years, mean injury severity score of 37.1 ± 2.4, and mean abdominal trauma index of 26.4 ± 2.1. Average initial base deficit was 15.7 ± 0.6 and 24-hour red cell transfusions were 20.4 ± 2.4 units. Of the 51 patients, 29 followed the protocol and 100% had fascial closure. Of the 22 patients who did not follow the protocol, 12 (55%) attained fascial closure. There were no significant differences in injury severity score, abdominal trauma index, base deficit, or red cell transfusions between the two groups. Conclusions A methodical approach with sequential fascial closure achieves 100% fascial approximation in our experience. This technique reduces the morbidity of the open abdomen and the cost of either complex abdominal reconstruction or biological mesh insertion.

Cancer and Leukemia Group B conducted a phase II study to evaluate the safety and efficacy of a reduced-intensity conditioning regimen with allogeneic transplantation to treat patients with recurrent low-grade B cell malignancies. Patients over age 18 with a diagnosis of relapsed, chemotherapy-sensitive disease underwent transplantation with a matched sibling donor, and conditioning with cyclophosphamide (1 g/m(2)/day × 3) and fludarabine phosphate (25 mg/m(2)/day × 5). Graft-versus-host prophylaxis included cyclosporine or tacrolimus plus low-dose methotrexate. Forty-four evaluable patients with a median age of 53 and median of 2 prior regimens were accrued. Sixteen patients had follicular non-Hodgkin lymphoma and 28 had histologies including 7 indolent B cell lymphomas, 4 mantle cell, 15 chronic lymphocytic leukemia (CLL), and 2 prolymphocytic leukemia (PLL) patients. The 6-month treatment-related mortality (TRM) was 2.4% and 3-year TRM was 9%. Three-year event-free and overall survival were 0.75 and 0.81 for the follicular patients, 0.59 and 0.71 for the CLL/PLL patients, and 0.55 and 0.64 for the other histologies. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 29%, and extensive chronic GVHD was 18%. This report demonstrates that allogeneic sibling transplantation with a reduced-intensity conditioning regimen is safe and efficacious for patients with advanced indolent B cell malignancies enrolled on a Cooperative Group study.

BACKGROUND: Massive transfusion (MTP) protocol design is hindered by lack of accurate assessment of coagulation. Rapid thrombelastography (r-TEG) provides point-of-care (POC) analysis of clot formation. We designed a prospective study to test the hypothesis that integrating TEG into our MTP would facilitate goal-directed therapy and provide equivalent outcomes compared to conventional coagulation testing. STUDY DESIGN AND METHODS: Thiry-four patients who received more than 6 units of red blood cells (RBCs)/6 hours who were admitted to our Level 1 trauma center after r-TEG implementation (TEG) were compared to 34 patients admitted prior to TEG implementation (Pre-TEG). Data are presented as mean ± SEM. RESULTS: Emergency department pre-TEG versus TEG shock, and coagulation indices, were not different: systolic blood pressure (94 mmHg vs.101 mmHg), temperature (35.3°C vs. 35.9°C), pH (7.16 vs. 7.11), base deficit (−13.0 vs. −14.7), lactate (6.5 vs. 8.1), international normalized ratio (INR; 1.59 vs. 1.83), and partial thromboplastin time (48.3 vs. 57.9). Although not significant, patients with Injury Severity Score range 26 to 35 were more frequent in the pre-TEG group. Fresh-frozen plasma (FFP) : RBCs, platelets : RBCs, and cryoprecipitate (cryo) : RBC ratios were not significantly different at 6 or 12 hours. INR at 6 hours did not discriminate between survivors and nonsurvivors (p = 0.10), whereas r-TEG “G” value was significantly associated with survival (p = 0.03), as was the maximum rate of thrombin generation (MRTG; mm/min) and total thrombin generation (TG; area under the curve) (p = 0.03 for both). Patients with MRTG of more than 9.2 received significantly less components of RBCs, FFP, and cryo (p = 0.048, p = 0.03, and p = 0.04, respectively). CONCLUSION: Goal-directed resuscitation via r-TEG appears useful for management of trauma-induced coagulopathy. Further experience with POC monitoring could result in more efficient management leading to a reduction of transfusion requirements.

We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of fludarabine 150 mg/m2 plus intravenous busulfan 6.4 mg/kg. Both matched sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit antithymocyte globulin (ATG) 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9-5.8), treatment-related mortality (TRM) at 6 months and 2 years was 8% and 23%, respectively. Neither TRM nor the rates of acute GVHD (aGVHD) were different in those with sibling or MUD donors. Donor CD3 cell chimerism >90% at day +30 was achieved more often in patients with MUD than with matched sibling donors, 70% versus 23% (P < .0001). Median event-free suvival was higher in patients who achieved early full donor chimerism (14.2 versus 8 months, P = .0395). Allo-HCT using this reduced-intensity conditioning regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve event-free survival.

Preperitoneal pelvic packing/external fixation (PPP/EF) for controlling life-threatening hemorrhage from pelvic fractures is used widely in Europe but has not been adopted in North America. We hypothesized that PPP/EF arrests hemorrhage rapidly, facilitates emergent operative procedures, and ensures efficient use of angioembolization (AE).In 2004 we initiated a PPP/EF guideline for pelvic fracture patients with refractory shock requiring ongoing blood transfusion at our regional trauma center.Among 1,245 patients admitted with pelvic fractures, 75 consecutive patients underwent PPP/EF (age 42 ± 2 years and injury severity score 52 ± 1.5). Emergency department systolic blood pressure was 76 ± 2 mmHg and heart rate 119 ± 2 beats/min. Time to operation was 66 ± 7 minutes, and 65 patients (87%) underwent 3 ± 0.3 additional procedures. Blood transfusion before PPP/EF compared with the first postoperative 24 hours was 10 ± 0.8 units versus 4 ± 0.5 units (p0.05). The fresh frozen plasma-red blood cell ratio was 1:2. After PPP/EF, 10 patients (13%) underwent angioembolization with a documented blush; time to angioembolization was 10.6 ± 2.4 hours (range 1 to 38 hours). Mortality for all pelvic fractures was 8%, with 21% mortality in this high-risk group. There were no deaths due to acute hemorrhage.PPP/EF was effective in controlling hemorrhage from unstable pelvic fractures. None of these high-risk patients died due to pelvic bleeding. Secondary angioembolization was needed in a minority, permitting selective use of this resource-demanding intervention. Additionally, PPP/EF temporizes arterial hemorrhage, providing valuable transfer time for facilities without angiography. With other urgent operative interventions required in85% of patients, combining these procedures with PPP/EF for operative pelvic hemorrhage control appears to optimize patient care.

Background Bedside percutaneous tracheostomy (BPT) is a cost-effective alternative to open tracheostomy. Small series have consistently documented minimal morbidity, but BPT has yet to be embraced as the standard of care. Because this has been our preferred technique in the surgical ICU for more than 20 years, we reviewed our experience to ascertain its safety. We hypothesize that BPT has acceptably minimal morbidity, even in high-risk patients. Study Design Patients undergoing BPT from January 1998 to June 2008 were reviewed. High-risk patients were defined as those with cervical collar or halo, cervical spine injuries, systemic heparinization, positive end-expiratory pressure >10 cm H 2 O or fraction of inspired oxygen > 50%. Results During the study period, 1,000 patients underwent BPT (74% men; mean ± SEM age 46 ± 0.6 years; 70% trauma). BPT was performed 8.9 ± 0.2 days (mean ± SEM) after admission. Patients remained ventilator dependent for an additional 9.7 ± 0.4 days (mean ± SEM). There were 482 (48%) patients undergoing BPT who were considered high-risk: 1 risk category, 273 patients; 2 risk categories, 139 patients; 3 risk categories, 56 patients; 4 risk categories, 12 patients; 5 risk categories, 2 patients. Complications occurred in 14 (1.4%) patients. Early complications included tracheostomy tube misplacement requiring revision (n = 4), bleeding requiring intervention (n = 2), infection (n = 1), and procedure failure requiring cricothyroidotomy (n = 1). Late complications included persistent stoma requiring operative closure (n = 4) and subglottic stenosis (n = 2). There were 6 complications (1.2%) in normal risk and 8 complications (1.7%) in high-risk patients. There were no deaths related to BPT. Conclusions BPT in the surgical intensive care unit is a safe procedure, even in high-risk patients. We believe BPT is the new gold standard for patients requiring tracheostomy for mechanical ventilation.

Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD 19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma.

The existence of primary fibrinolysis (PF) and a defined mechanistic link to the "Acute Coagulopathy of Trauma" is controversial. Rapid thrombelastography (r-TEG) offers point of care comprehensive assessment of the coagulation system. We hypothesized that postinjury PF occurs early in severe shock, leading to postinjury coagulopathy, and ultimately hemorrhage-related death.Consecutive patients over 14 months at risk for postinjury coagulopathy were stratified by transfusion requirements into massive (MT)10 units/6 hours (n = 32), moderate (Mod) 5 to 9 units/6 hours (n = 15), and minimal (Min)5 units/6 hours (n = 14). r-TEG was performed by adding tissue factor to uncitrated whole blood. r-TEG estimated percent lysis was categorized as PF when15% estimated percent lysis was detected. Coagulopathy was defined as r-TEG clot strength = G5.3 dynes/cm. Logistic regression was used to define independent predictors of PF.A total of 34% of injured patients requiring MT had PF, which was associated with lower emergency department systolic blood pressure, core temperature, and greater metabolic acidosis (analysis of variance, P0.0001). The risk of death correlated significantly with PF (P = 0.026). PF occurred early (median, 58 minutes; interquartile range, 1.2-95.9 minutes); every 1 unit drop in G increased the risk of PF by 30%, and death by over 10%.Our results confirm the existence of PF in severely injured patients. It occurs early (1 hour), and is associated with MT requirements, coagulopathy, and hemorrhage-related death. These data warrant renewed emphasis on the early diagnosis and treatment of fibrinolysis in this cohort.

Progressive postinjury coagulopathy remains the fundamental rationale for damage control surgery, but the decision to abort operative intervention must occur before laboratory confirmation of coagulopathy. Current massive transfusion protocols have embraced pre-emptive resuscitation strategies emphasizing administration of packed red blood cells, fresh frozen plasma, and platelets in ratios approximating 1:1:1 during the first 24 hours postinjury, based on US military retrospective experience and recent noncontrolled civilian data. This policy, termed "damage control resuscitation" assumes that patients presenting with life threatening hemorrhage at risk for postinjury coagulopathy should receive component therapy in rations approximating those found in whole blood during the first 24 hours. While we concur with the concept of pre-emptive coagulation factor replacement, and initially suggested this in 1982, we remain concerned for the continued unbridled administration of fresh frozen plasma and platelets without objective evidence of their specific requirement. A major limitation of current massive transfusion protocols is the lack of real time assessment of coagulation function to guide evolving blood component requirements. Existing laboratory coagulation testing was originally designed for evaluation of hemophilia and subsequently used for monitoring anticoagulation therapy. Consequently, the applicability of these tests in the trauma setting has never been proven and the time required to conduct these assays is incompatible with prompt correction of the coagulopathy in the trauma setting. This review examines the current approach to postinjury coagulopathy, including identification of patients at risk, resuscitation strategies, design and implementation of institutional massive transfusion protocols, and the potential benefits of goal-directed therapy by real time assessment of coagulation function via point of care rapid thromboelastography.

BACKGROUND: Life-threatening hemorrhage is a rare event in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Epidemiologic data are lacking to predict patients at risk for hemorrhage requiring surgical consultation. We sought to identify early clinical predictors of hemorrhagic complications in patients at risk for HELLP syndrome. METHODS: Patients at risk for HELLP syndrome from 1997 to 2007 were identified retrospectively. Variables evaluated in at-risk women were maternal age, gestational history, hepatic transaminase levels, and platelet count. Multiple logistic regression analysis was used to identify independent predictors of poor maternal outcomes, which were defined as hemorrhage requiring transfusion of blood products, need for surgical intervention, hepatic rupture, and death. RESULTS: A total of 109 at-risk women were identified. Adverse outcomes included transfusions (18%), hemorrhage interventions (8%), damage control laparotomy (2.8%), and hepatic rupture (2.8%). Maternal and perinatal mortality were .9% and 3.7%, respectively. Median transfusion requirements for women with hepatic rupture were 56 U of packed red blood cells, 26 U of fresh-frozen plasma, 18 U of platelets, and 6 U of cryoprecipitate. Multiple logistic regression analysis showed previous gestations (P = .002), platelet count (P = .01), and aspartate aminotransferase level increase (P = .04) were independent predictors of life-threatening hemorrhage. Previous gestations increased the risk of adverse outcome 3-fold. CONCLUSIONS: Identifiable risk factors predictive of major hemorrhage are thrombocytopenia (< 100,000 cells/μL), increase of aspartate aminotransferase level greater than 70 IU/L, and previous gestations.

Introduction. Progressive postinjury coagulopathy has become the fundamental rationale for damage control surgery, and the decision to abort operative intervention must occur prior to overt laboratory confirmation of coagulopathy. Current coagulation testing is most commonly performed for monitoring anticoagulation therapy, the results are delayed, and the applicability of these tests in the trauma setting is questionable. Point-of-care (POC) rapid thrombelastography (r-TEG) provides real time analysis of thrombostatic function, which may allow for accurate, goal directed therapy. The test differs from standard thrombelastography (TEG) because the clotting process and subsequent analysis is accelerated by the addition of tissue factor to the whole blood sample, but is limited by the requirement that the analysis be performed within 4 min of blood draw to prevent clot formation. Consequently, citrated specimens have been proposed to obviate this time limitation. We hypothesized that the speed of r-TEG analysis following tissue factor addition to citrated blood might compromise accurate determinations compared with noncitrated whole blood. Additionally, we sought to compare the use of r-TEG with conventional coagulation tests in analysis of postinjury coagulopathy. Methods. We conducted a retrospective study of severely injured patients entered into our trauma database between January and June 2008 who were at risk for postinjury coagulopathy. Patients needed simultaneous conventional coagulation (INR, fibrinogen, platelet count) and r-TEG specimens with either fresh or citrated whole blood for inclusion in the study. κ-Statistics were used to determine the agreement between the tests in predicting hypocoagulability. McNemar's x 2 tests were used to compare theoretical blood product administration between r-TEG and conventional coagulation tests for noncitrated specimens. Therapeutic transfusion triggers were: INR ( >1.5) and r-TEG ACT ( > 125 s) for FFP administration; fibrinogen (

Background Recent guidelines do not support local wound exploration (LWE) or diagnostic peritoneal lavage (DPL) in the evaluation of patients with anterior abdominal stab wounds (AASWs), favoring computed tomography scanning or serial examinations. In patients without immediate indications for laparotomy, we hypothesized that LWE/DPL would identify patients requiring surgery while limiting unnecessary hospital admissions. Methods Patients sustaining penetrating trauma at our level I trauma center over a 3-year period were reviewed. Results During the study period, 139 patients with AASW followed our LWE/DPL algorithm. Fifty-six patients had LWE without fascial penetration: 46 were discharged immediately, 10 required admission. Fifty-eight patients had fascial penetration on LWE but negative DPL: 37 were observed for less than 24 hours, 19 were observed for more than 24 hours, and 2 patients developed peritonitis requiring exploration. Twenty-five patients had positive LWE/DPL: 13 had therapeutic laparotomy, 12 had nontherapeutic laparotomy. Conclusions Only 11% of patients with AASWs without overt indication for laparotomy require surgical care. LWE remains a valid method to exclude intra-abdominal injury and to eliminate hospitalization in more than one third of AASW patients.

High-mobility group box 1 (HMGB1) is a late mediator of the systemic inflammation associated with sepsis. Recently, HMGB1 has been shown in animals to be a mediator of hemorrhage-induced organ dysfunction. However, the time course of plasma HMGB1 elevations after trauma in humans remains to be elucidated. Consequently, we hypothesized that mechanical trauma in humans would result in early significant elevations of plasma HMGB1. Trauma patients at risk for multiple organ failure (ISS > or = 15) were identified for inclusion (n = 23), and postinjury plasma samples were assayed for HMGB1 by enzyme-linked immunosorbent assay. Comparison of postinjury HMGB1 levels with markers for patient outcome (age, injury severity score, units of red blood cell (RBC) transfused per first 24 h, and base deficit) was performed. To investigate whether postinjury transfusion contributes to elevations of circulating HMGB1, levels were determined in both leuko-reduced and non-leuko-reduced packed RBCs. Plasma HMGB1 was elevated more than 30-fold above healthy controls within 1 h of injury (median, 57.76 vs. 1.77 ng/mL; P < 0.003), peaked from 2 to 6 h postinjury (median, 526.18 ng/mL; P < 0.01 vs. control), and remained elevated above control through 136 h. No clear relationship was evident between postinjury HMGB1 levels and markers for patient outcome. High-mobility group box 1 levels increase with duration of RBC storage, although concentrations did not account for postinjury plasma levels. Leuko-reduced attenuated HMGB1 levels in packed RBCs by approximately 55% (P < 0.01). Plasma HMGB1 is significantly increased within 1 h of trauma in humans with marked elevations occurring from 2 to 6 h postinjury. These results suggest that, in contrast to sepsis, HMGB1 release is an early event after traumatic injury in humans. Thus, HMGB1 may be integral to the early inflammatory response to trauma and is a potential target for future therapeutics.

Most multiple organ failure (MOF) scores were developed over a decade ago, but little has been done in terms of validation and to understand the differences between populations identified by each of them. Given the lack of a gold standard, validation must rely on association with objective adverse outcomes. Thus, we propose to (a) validate two widely accepted MOF scores (Denver and Marshall), examining their association with adverse outcomes in a postinjury population; and (b) compare risk factors, characteristics, and outcomes of patients identified by each score. The Denver MOF score grades (from 0-3) four organ dysfunctions (lung, kidney, liver, and heart) and defines MOF as a total score more than 3. The Marshall score grades, in addition, central nervous system and hematologic dysfunction (total of six organs on a 0- to 4-point scale). Using a prospectively collected data set, MOF was scored daily by both scores for 1,389 consecutive trauma patients with Injury Severity Score of more than 15 admitted from 1992 to 2004. Risk factors, clinical outcomes (death, ventilator-free days), and resource utilization outcomes (mechanical ventilation time, length of stay in the intensive care unit) were evaluated. Both scores were associated with areas under the receiver operating characteristic curves of 80 or greater (ideal value = 100), with values for the Denver score being slightly greater (albeit not significantly) regarding prediction of most outcomes. Values of sensitivity and specificity were more than 70% for death and ventilator-free days (with the Denver score showing a consistent trend toward greater specificity), but either sensitivity or specificity was less than 70% for mechanical ventilation time and length of stay in the intensive care unit, suggesting that these scores are appropriately biased toward clinical outcomes as opposed to resource utilization. Both scores performed well, with the Denver MOF score showing greater specificity, which, coupled with its simplicity, makes it an attractive tool for both the research and clinical environments. Basic concepts of each score can probably be combined to produce an improved MOF score.

Background: Concurrent chemo- and radiotherapy improves outcome of certain human neoplasms but with increased signs of toxicity. Reports on adverse effects of concurrent chemo- and radiotherapy in the veterinary literature are scant. Objective: To report adverse hematologic and gastrointestinal effects of combined carboplatin and radiation therapy in dogs. Animals: Client-owned dogs with spontaneously occurring neoplasia. Methods: Retrospective case study. Medical records of 65 dogs were reviewed. Criteria for inclusion were administration of radiation according to 1 of 3 fractionation schemes (19 × 3, 16 × 3, or 12 × 4 Gy) and administration of at least 1 concurrent carboplatin treatment at a dosage of 200–300 mg/m2. Dog and treatment-related variables were analyzed for association with signs of intoxication. Results: Median carboplatin dosage was 200 mg/m2 (range, 200–250 mg/m2). Twelve of 58 dogs (21%) developed grade 3 or 4 neutropenia. Eleven of 56 dogs (20%) developed grade 3 or 4 thrombocytopenia. Six of 62 dogs (10%) developed grade 3, 4, or 5 gastrointestinal toxicosis. Analysis of association of dog and treatment-related variables with signs of intoxication was hampered by the small numbers of dogs in individual groups, and no statistically significant associations were found. Conclusions and Clinical Importance: Combined modality therapy resulted in myelosuppression and gastrointestinal toxicosis. Future studies are needed to determine whether the potential benefit of combined modality therapy outweighs the risk of decreasing chemotherapy and radiation treatment intensity.

Recent military experience suggests that immediate 1:1 fresh frozen plasma (FFP); red blood cells (RBC) for casualties requiring10 units packed red blood cells (RBC) per 24 hours reduces mortality, but no clinical trials exist to address this issue. Consequently, we reviewed our massive transfusion practices during a 5-year period to test the hypothesis that 1:1 FFP:RBC within the first 6 hours reduces life threatening coagulopathy.We queried our level I trauma center's prospective registry from 2001 to 2006 for patients undergoing massive transfusion. Logistic regression was used to evaluate the independent effect of FFP:RBC in 133 patients who received10 units RBC in 6 hours on (1) Coagulopathy (international normalized ratio [INR]1.5 at 6 hours), controlling for our previously described risk factors predictive of coagulopathy, as well as RBC, FFP, and platelet administration (2) Death (controlling for all variables plus age, crystalloids per 24 hours, INR1.5 at 6 hours).Overall mortality was 56%; 50% died from acute blood loss in the operating room. Over 80% of the RBC transfusions were completed in the first 6 hours: (Median RBC: 18 units) Median FFP:RBC survivors, 1:2, nonsurvivors: 1:4. (p0.001) INR1.5 at 6 hours occurred in 30 (23%); 81% died. Regarding mortality, logistic regression showed significant variables (p0.05) included: RBC per 6 hours (OR = 1.248, 95%CI: 1.957-53.255), INR at 6 hours1.5 (OR = 10.208, 95% CI: 1.957-53.255), ED temperature34 degrees C (OR = 15.491, 95% CI 1.376-174.396), and age55 years (OR = 40.531, CI 5.315-309.077). The adjusted OR for FFP:RBC ratio including the quadratic term was found to follow a U-shaped association (quadratic term estimate 0.6737 +/- 0.0345, p = 0.0189).Although our data suggest that 1:1 FFP:RBC reduced coagulopathy, this did not translate into a survival benefit. Our findings indicate that the relationship between coagulopathy and mortality is more complex, and further clinical investigation is necessary before recommending routine 1:1 in the exsanguinating trauma patient.

Purpose The 111 In-capromab pendetide scan (ProstaScint; Cytogen Corp., Princeton NJ) is approved by the Food and Drug Administration to evaluate increasing prostate-specific antigen (PSA) levels after radical prostatectomy. This study evaluated the role of prostate bed 111 In-capromab pendetide scan findings to predict response to salvage radiotherapy (RT). Methods and Materials Forty patients who had PSA recurrence after radical prostatectomy and a 111 In-capromab pendetide scan immediately before salvage prostate bed RT (median, 66 Gy) were identified from the Duke Prostate Center database. Patients with distant uptake of capromab pendetide or long-term androgen deprivation therapy were excluded. Median follow-up after salvage RT was 2.7 years. Patient demographic, clinical, and pathologic characteristics; PSA values; and 111 In-capromab pendetide scan results were retrospectively analyzed. A PSA failure after salvage RT was defined as PSA level greater than 0.2 ng/ml. Data were combined with other published results in a secondary pooled analysis of 106 patients. Results 111 In-Capromab pendetide findings included 20 patients with negative scan results and 20 with locally positive scan results. Two-year progression-free survival rates were 60% for patients with a negative scan result and 74% for those with a locally positive scan result ( p = 0.49). Combined analysis did not show a difference in outcome based on local 111 In-capromab pendetide scan result. Conclusion For patients without distant signal detected by using 111 In-capromab pendetide scan, patients with locally positive scan findings did not have statistically different progression-free survival than those with a negative scan result, suggesting that salvage RT may be successful in patients with either a locally positive or negative 111 In-capromab pendetide scan result.

Background Secondary abdominal compartment syndrome (SACS) is a well-recognized sequelae of massive fluid resuscitation in surgical patients, but has only anecdotally been reported in the medical patient population. The purpose of this study was to compare the clinical scenarios, physiologic indices, and outcomes of patients with SACS due to medical versus trauma etiologies. Methods Patients undergoing decompression for SACS from January 1999 to January 2006 were identified using our computerized operative records. Results During the 7-year study period, 54 patients developed SACS (41 postinjury patients and 13 medical patients). There were no significant differences in demographics, physiologic indices, or fluid resuscitation between the medical and postinjury groups: age (46.6 ± 4.7 vs 40.6 ± 2.3), bladder pressure (33.5 ± 1.1 vs 32.8 ± 1.8), peak airway pressures (45.9 ± 2.4 vs 49.3 ± 2.1), base deficit (14.6 ± 1.4 vs 13.6 ± 1.1), and fluids (18.5 ± 1.8 vs 16.0 ± 1.5 liters). Patients with a medical cause of SACS had a significantly longer time to decompression (21 ± 3.6 versus 6.5 ± 1.9 hours), significantly higher incidence of MOF (62% v 27%), and trend toward greater mortality (54% versus 34%). Conclusions Patients with diverse disease processes may develop SACS. Despite similar age and physiologic indices, the MOF and mortality rates associated with medical SACS are markedly higher. These findings highlight the need for routine monitoring in at-risk patients, prevention of pathologic intra-abdominal hypertension, and a low threshold for decompression.

Restoring oxygen delivery to ischemic organs after hemorrhagic shock is a fundamental goal of postinjury resuscitation. Currently, crystalloid resuscitation followed by transfusion of packed red blood cells (PRBCs) remains the standard of care; however, stored PRBC transfusion is not without adverse consequences. Allogenic blood transfusion for hemorrhagic shock has been linked to increased infection rates,1 and recent clinical studies indicate that the volume and timing of blood transfusion can increase the recipient's risk for developing postinjury multiple organ failure (MOF): specifically, transfusion of greater than 6 units of PRBC in the first 12 hours postinjury has been shown to be an independent risk factor for MOF, irrespective of the severity.2,3 The precise mechanisms in the pathogenesis of MOF remain unclear, and identification of these risk factors suggests that blood transfusion delivers an incremental insult contributing to a dysregulated systemic inflammatory response.4,5 Although it is known that stored red blood cells progressively change in size and shape with age,6 in vitro and clinical studies have offered greater insight into the proinflammatory effects of blood transfusion. Several bioactive substances accumulate with blood storage, including cytokines and proinflammatory lipids.7–9 Others have shown that there are extractable agents found in PRBC that can directly cause increased lung leak.10 Although removing leukocytes from stored PRBCs can reduce cytokine accumulation, proinflammatory lipids remain unfiltered. Furthermore, clinical studies demonstrate that despite leukoreduction, patients continue to experience adverse outcomes associated with transfusion.11–16 Conversely, avoiding PRBCs with the use of acellular hemoglobin-based oxygen carriers (HBOCs) to resuscitate severely injured patients is associated with a significantly lower systemic inflammatory response.17 In sum, it would seem that the predominant mechanism for the proinflammatory effect of PRBC transfusion lies in the interplay between the bioactive substances found in stored blood and the body's immune cells. Therefore, we think it is important to better understand how PRBCs affect the recipient's immune system, particularly in trauma where large-volume blood transfusions are common. In this study, we simulate major postinjury transfusion ex vivo and investigate the effect of PRBCs on circulating leukocyte gene expression. We hypothesize that PRBC transfusion induces inflammatory gene expression.

Nelarabine (506U78) is a soluble pro-drug of 9-β-d-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m2/day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL.

Background: Because of high single-agent activity and modest toxicity, we hypothesized the combination of gemcitabine (G), vinorelbine (V), and pegylated liposomal doxorubicin (D) would be an effective salvage therapy for Hodgkin's lymphoma (HL). Patients and methods: A total of 91 patients participated. GVD was administered on days 1 and 8 every 21 days at doses of G 1000 mg/m2, V 20 mg/m2, and D 15 mg/m2 for transplant-naive patients, and G 800 mg/m2, V 15 mg/m2, and D 10 mg/m2 for post-transplant patients. Results: The dose-limiting toxicity was mucositis for the transplant-naive patients and febrile neutropenia for post-transplant patients. The overall response rate (RR) for all patients was 70% [95% confidence interval (CI) 59.8, 79.7], with 19% complete remissions. The 4-year event-free and overall survival rates in transplant-naive patients treated with GVD followed by autologous transplant were 52% (95% CI 0.34, 0.68) and 70% (95% CI 0.49, 0.84), and in the patients in whom prior transplant failed, these were 10% (95% CI 0.03, 0.22) and 34% (95% CI 0.17, 0.52), respectively. Conclusions: GVD is a well-tolerated, active regimen for relapsed HL with results similar to those reported for more toxic regimens. High RRs in patients in whom prior transplant failed confirms this regimen's activity even in heavily pretreated patients.

The current management of pelvic fracture patients who are hemodynamically unstable in the United States consists of aggressive resuscitation, mechanical stabilization, and angioembolization. Despite this multidisciplinary approach, our recent analysis confirms an alarming 40% mortality in these high-risk patients. Therefore, we pursued alternate therapies to improve patient outcomes. European trauma groups have suggested the technique of pelvic packing via laparotomy to directly address the venous bleeding that comprises 85% of pelvic fracture hemorrhage. We hypothesized that a modified technique of direct preperitoneal pelvic packing (PPP) would reduce the need for angiography, decrease blood transfusion requirements, and lower mortality.Since September 2004, all patients at our ACS-verified level I trauma center with hemodynamic instability and pelvic fractures underwent PPP/external fixation, according to our protocol. Statistics are reported as mean +/- SEM and analyzed using Student's t test.During the study period, 28 consecutive patients underwent PPP. There was one protocol deviation of prePPP angiography to evaluate an extremity vascular injury. The majority were men (68%) with a mean age of 40 +/- 3.9 years and a mean injury severity score of 55 +/- 3.0. The mean emergency department (ED) systolic blood pressure was 77 +/- 3.0 mm Hg, heart rate was 120 +/- 4.3 bpm, and base deficit 13 +/- 0.8 mmol/L. Pelvic fracture classifications included lateral compression (LC) II (9), anteroposterior compression (APC) III (8), LC I (3), vertical shear (3), LC III (3), and APC II (2). Patients required 4 +/- 1.2 units of packed red blood cells (PRBCs) during 82 +/- 13 minutes in the ED. Blood transfusion requirements before postoperative surgical intensive care unit (SICU) admission compared with the subsequent 24 postoperative hours were significantly different (12 +/- 2.0 versus 6 +/- 1.1; p = 0.006). The first 4 patients underwent routine angiography postPPP, with 1 undergoing therapeutic embolization; 4 of the subsequent 24 patients underwent angioembolization with clinical concern of ongoing pelvic hemorrhage. Seven (25%) patients died from multiple organ failure (2), postinjury myocardial infarction/pulseless electrical activity (PEA) arrest (2), invasive mucormycosis (1), withdrawal of care (1), and closed head injury (1); there were no deaths as a result of acute blood loss.PPP is a rapid method for controlling pelvic fracture-related hemorrhage that can supplant the need for emergent angiography. There is a significant reduction in blood product transfusion after PPP, and this approach appears to reduce mortality in this select high-risk group of patients.