Erwin F. Hirsch

Prospective Study of Blunt Aortic Injury: Multicenter Trial of the American Association for the Surgery of Trauma

BACKGROUND Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. METHODS This study was a prospectively conducted multi-center trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. RESULTS There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of > or = 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. CONCLUSIONS Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.

Penetrating esophageal injuries: Multicenter study of the American Association for the Surgery of Trauma

OBJECTIVE The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fishers exact test, Students T test, and logistic regression analysis. RESULTS The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients

Normal‐appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer‐free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal‐lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age‐matched women without breast disease (n = 15)). Cyber‐T identified differentially expressed genes. Quantitative RT‐PCR (qRT‐PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two‐thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G‐protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under‐expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer‐related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissues response to an existing tumor.

Fracture locations influence the likelihood of rectal and lower urinary tract injuries in patients sustaining pelvic fractures.

BACKGROUND Rectal and lower urinary tract injuries in pelvic fractures can lead to significant complications. We sought to determine whether fracture locations could serve as markers for injury. METHODS In our retrospective review of patients with blunt pelvic fractures, the association of fracture locations with injury to the rectum, bladder, and urethra was explored with Fishers exact test and subsequently analyzed with multiple logistic regression. RESULTS Of the 362 patients reviewed, 8 had rectal injury and 24 had lower urinary tract injury. The following locations were found to be significant. Rectum: symphysis pubis (relative risk [RR] = 3.3, p < 0.001) and sacroiliac (SI) joint (RR = 2.1, p = 0.014). Bladder: symphysis pubis (RR = 2.1, p < 0.001), SI joint (RR = 2.0, p < 0.001), and sacrum (RR = 1.6, p = 0.002). Urethra: symphysis pubis (RR = 2.9, p = 0.003), SI joint (RR = 1.8, p = 0.04), and inferior ramus (RR = 4.6, p = 0.008). After multivariate analysis, the primary and independent predictors for each of the injuries were as follows: rectal injury, widened symphysis; bladder injury, widened symphysis and SI joint; and urethral injury, widened symphysis and fracture of the inferior pubic ramus. Although these associations were significant, the overall prevalence of associated rectal and urologic injuries was low. Consequently, the predictive values of these radiologic findings were also low, ranging from 5% to 9% for urethral and rectal injuries to 20% for bladder injuries. CONCLUSION Certain fracture locations are associated with increased risk for rectal, bladder, or urethral injury. Fractures involving these locations should prompt further work-up for assessment.

New approaches to the management of severe acute pancreatitis

A recent experience with seventy-seven patients admitted to Boston City Hospital for acute pancreatitis permitted us to identify thirteen patients (17 per cent) whom we diagnosed as having severe protracted acute pancreatitis. These alcoholic patients obviously had fulminant pancreatitis similar to that reported by others in two instances and pancreatic abscesses in two additional instances, but nine of the patients did not fulfill the criteria usually used by others as a basic for surgical intervention. Specific preoperative diagnosis was obtained in these patients by the aggressive use of endoscopic cannulation of the pancreatic ducts, which documented the presence of surgically correctable lesions. These patients had sustained significant malnutrition, which was corrected only by protracted therapy extending an average of two months and involving all modalities currently available for nutritional support of the severely ill patient. After proper preoperative identification of a specific lesion and correction of the malnutrition, the eleven patients without fulminant disease were operated on with no deaths or significant complication. Nine of the patients had elective procedures, which included six distal pancreatectomies and one total pancreatectomy. Thus, severe protracted acute pancreatitis can be identified, and once categrorized, it can have therapeutic implications.

Clinical clearance of the cervical spine in blunt trauma patients younger than 3 years: A multi-center study of the american association for the surgery of trauma

BACKGROUND Cervical spine clearance in the very young child is challenging. Radiographic imaging to diagnose cervical spine injuries (CSI) even in the absence of clinical findings is common, raising concerns about radiation exposure and imaging-related complications. We examined whether simple clinical criteria can be used to safely rule out CSI in patients younger than 3 years. METHODS The trauma registries from 22 level I or II trauma centers were reviewed for the 10-year period (January 1995 to January 2005). Blunt trauma patients younger than 3 years were identified. The measured outcome was CSI. Independent predictors of CSI were identified by univariate and multivariate analysis. A weighted score was calculated by assigning 1, 2, or 3 points to each independent predictor according to its magnitude of effect. The score was established on two thirds of the population and validated using the remaining one third. RESULTS Of 12,537 patients younger than 3 years, CSI was identified in 83 patients (0.66%), eight had spinal cord injury. Four independent predictors of CSI were identified: Glasgow Coma Score <14, GCSEYE = 1, motor vehicle crash, and age 2 years or older. A score of <2 had a negative predictive value of 99.93% in ruling out CSI. A total of 8,707 patients (69.5% of all patients) had a score of <2 and were eligible for cervical spine clearance without imaging. There were no missed CSI in this study. CONCLUSIONS CSI in patients younger than 3 years is uncommon. Four simple clinical predictors can be used in conjunction to the physical examination to substantially reduce the use of radiographic imaging in this patient population.

Blood insulin responses to blood glucose levels in high output sepsis and septic shock

To determine whether the secretion of insulin in severe sepsis is impaired as it is in hypovolemic shock, simultaneous determinations were made of cardiac output, blood glucose, insulin, alanine, and lactate in thirty-eight patients seriously infected with enteric and other organisms. Of these, seventeen were in the low output shock state with a mean cardiac index (CI) of 1.78 ± 0.48 L/M2/min. The remaining twenty-one were in the high output pattern characteristic of recovery with a mean cardiac index of 4.08 ± 0.82 L/M2/min. There were only modest differences within either group of any measured parameters dependent upon whether the patient was receiving an intravenous glucose infusion. However, in the whole group of patients with low CI the blood insulin was 9 ± 5 μU/ml, while in those with high CI the blood insulin was 38 ± 21 μU/ml. Cluster analysis gave a highly significant difference between the two groups with determinant weights: insulin, 77 per cent; glucose, 12 per cent; alanine, 9 per cent; and lactate, 2 per cent. For comparison with the normal insulin response, data derived from oral glucose tolerance tests in thirty-five healthy nondiabetic adults were employed. Analysis of the log10 insulin/log10 glucose ratios disclosed highly significant differences (p < 0.001) between the low CI and normal or high CI group. The difference between the high CI and normal was just significant (p < 0.05). It is concluded that both a slight reduction of insulin secretion and an insulin resistance are probably responsible for the pseudodiabetes observed in patients who are in the high CI pattern of recovery.

Blunt pancreatoduodenal injury: A multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT)

OBJECTIVES To evaluate the safety of nonoperative management (NOM), to examine the diagnostic sensitivity of computed tomography (CT), and to identify missed diagnoses and related outcomes in patients with blunt pancreatoduodenal injury (BPDI). DESIGN Retrospective multicenter study. SETTING Eleven New England trauma centers (7 academic and 4 nonacademic). PATIENTS Two hundred thirty patients (>15 years old) with BPDI admitted to the hospital during 11 years. Each BPDI was graded from 1 (lowest) to 5 (highest) according to the American Association for the Surgery of Trauma grading system. MAIN OUTCOME MEASURES Success of NOM, sensitivity of CT, BPDI-related complications, length of hospital stay, and mortality. RESULTS Ninety-seven patients (42.2%) with mostly grades 1 and 2 BPDI were selected for NOM: NOM failed in 10 (10.3%), 10 (10.3%) developed BPDI-related complications (3 in patients in whom NOM failed), and 7 (7.2%) died (none related to failure of NOM). The remaining 133 patients were operated on urgently: 34 (25.6%) developed BPDI-related complications and 20 (15.0%) died. The initial CT missed BPDI in 30 patients (13.0%); 4 of them (13.3%) died but not because of the BPDI. The mortality rate in patients without a missed diagnosis was 8.8% (P = .50). There was no correlation between time to diagnosis and length of hospital stay (Spearman r = 0.06; P = .43). The sensitivity of CT for BPDI was 75.7% (76% for pancreatic and 70% for duodenal injuries). CONCLUSIONS The NOM of low-grade BPDI is safe despite occasional failures. Missed diagnosis of BPDI continues to occur despite advances in CT but does not seem to cause adverse outcomes in most patients.

Prostanoid production by lipopolysaccharide-stimulated Kupffer cells☆

Although some data suggest that macrophages in the reticuloendothelial system (RES) are important sources of thromboxane A2 (TxA2) and prostacyclin (PGI2) during endotoxic shock, we are unaware of data documenting the ability of hepatic macrophages (Kupffer cells) to release either TxA2 or PGI2 when exposed to lipopolysaccharide (endotoxin, LPS). In this study, Kupffer cells were examined for their ability to release prostaglandin E2 (PGE2), TxA2, and PGI2 following stimulation with 0, 1.0, 50.0, and 100.0 micrograms/ml of Escherichia coli LPS. Kupffer cells were obtained from rat livers by enzymatic digestion with 0.05% collagenase followed by enrichment of the macrophage population on the basis of differences in density and adherence among the various cell populations isolated. Based on several criteria (phagocytosis of opsonized sheep erythrocytes, positive staining for esterase and peroxidase, failure to replicate), 95% of adherent cells were Kupffer cells. After 4 days of incubation, cells were stimulated with various doses of LPS for 4 and 8 hr. Prostanoid concentrations in culture supernatants were determined by radioimmunoassay. Increasing doses of LPS significantly (P less than 0.001) increased the concentration of immunoreactive PGE2 (iPGE2) and iTxB2 (the stable metabolite of TxA2). The concentration of i6-keto-PFG1 alpha (stable metabolite of PGI2) increased following stimulation with 1.0 microgram/ml of LPS, but declined as the dose of LPS was increased. The results provide evidence that endotoxin-activated Kupffer cells, like other macrophage populations, release several metabolites of arachidonic acid. Kupffer cell-derived prostanoids, particularly TxA2, may be important mediators of some of the pathophysiologic manifestations of acute endotoxemia.

Emergency room thoracotomy for penetrating chest injury: effect of an institutional protocol.

BACKGROUND Emergency room thoracotomy (ERT) can be life saving in patients with penetrating chest injury. A protocol was established at our institution stating that ERT be performed for cases of cardiac tamponade secondary to penetrating chest trauma on patients with vital signs/mentation in the field or on arrival to the emergency room. To validate our protocol, we reevaluated patients undergoing ERT at our institution. METHODS In our retrospective review, there were 49 patients undergoing ERT over a 6-year period. RESULTS Survival in patients with vital signs was approximately 50%. Survival in those without was 0%. Compared with the preprotocol data, the number of ERTs declined from 32.2 cases per year to 8.1 cases per year. Overall survival increased from 4% to 20%. Neurologic outcome remained unchanged. CONCLUSION We believe that the data validate our protocol, and the establishment of a guideline has enabled us to maximize patient survival and minimize exposure risks to our staff.