E. Darrin Cox, MD | Uniformed Services University (original) (raw)

Papers by E. Darrin Cox, MD

CHEST Journal, 2004

INTRODUCTION: The role of surgical management in T4 non-small cell lung cancer (NSCLC) remains co... more INTRODUCTION: The role of surgical management in T4 non-small cell lung cancer (NSCLC) remains controversial. Treatment is usually palliative, yet a certain proportion of patients may benefit from curative treatment. We report on radical en bloc resection of a right upper lobe (RUL) NSCLC invading the 3rd and 4th thoracic vertebrae. CASE PRESENTATION: A 51-year-old white male smoker developed right shoulder and upper back pain. Initial conservative management failed to resolve the pain. Plain films revealed degenerative joint disease. The pain persisted. Computed tomography (CT) and magnetic resonance imaging showed a 5 x 5.1 cm RUL mass invading the right T3-T4 neural foramen and a portion of the T2 vertebral body. CT-guided biopsy revealed squamous cell carcinoma, and mediastinoscopy was negative for N2 disease. Clinical stage was T4N0M0 (Stage IIIB) NSCLC. After neoadjuvant therapy (Taxol/Cisplatin and 5000 cGy), a Neotec scan revealed no evidence of distant disease. Pulmonary function tests were normal. Repeat imaging studies showed no evidence of cord compression and partial tumor response. The patient was taken to the operating room where he underwent radical en bloc resection of the tumor, which included a right upper lobectomy, chest wall and three level vertebrectomy. Spinal integrity was achieved by anterior cage reconstruction followed by posterior rod stabilization. A complete resection was achieved histologically. Three years later, he is well, without radiologic or clinical evidence of recurrence. DISCUSSIONS: Surgery remains the 'gold standard' for early-stage lung cancer. Stage IIIB NSCLC is considered an inoperable disease; however, Stage IIIB represents a heterogeneous group of patients, including the subgroup of T4N0M0 patients. These patients may benefit from an aggressive surgical approach, oftentimes after neoadjuvant therapy. Several authors have described acceptable outcomes after surgical treatment. DeMeester, et al (1) reported 12 patients with T4N0M0 NSCLC with tumor adherent to the vertebral column who underwent preoperative radiotherapy and radical surgical excision with a 5-year Kaplan-Meier survival of 42%. Grunenwald et al (2) demonstrated a 14% predicted 5-year survival in 19 patients undergoing en bloc partial and total vertebrectomy for lung cancer invading the spine. Other authors (34567) have reported 5-year survival rates ranging from 10-28% in a heterogeneous group of T4 lung cancer patients. Operative morbidity and mortality have been acceptable in this high-risk group of patients. Factors contributing to long-term survival appear to include response to neoadjuvant therapy, ability to achieve complete histologic resection, and absence of N2 or N3 nodal disease. CONCLUSION: The role of surgery for Stage IIIB NSCLC remains controversial. Various authors have advocated surgical therapy for certain subsets of Stage IIIB NSCLC. We present a case of T4N0M0 NSCLC invading several levels of the thoracic vertebrae. Aggressive en bloc surgical resection and reconstruction after neoadjuvant therapy resulted in a negative margin resection and long-term survival.

Annals of Emergency Medicine, 2007

Annals of Emergency Medicine, 2008

Study Objectives: The incidence of obesity has reached epidemic proportions in the United States.... more Study Objectives: The incidence of obesity has reached epidemic proportions in the United States. The impact of this comorbid condition on the likelihood of injury in the trauma patient is unknown. In this study, the relative risk of cervical spine injury was determined for a population of obese blunt trauma patients as compared to a nonobese cohort. Methods: A retrospective analysis of an electronic patient database at a Level 1 trauma center with a large referral base of patients with cervical spine injuries was conducted for the period from September 1, 2005 to December 31, 2007. In addition to standard demographic characteristics, information with regard to cervical spine injury and body mass index (BMI) were collected for each patient with blunt trauma who met the criteria for a trauma activation or trauma consultation due to significant injury. The patients were then divided into the categories of obese and nonobese based on the World Health Organization classification (BMI cutoff of 30). The relative risk of cervical spine injury in the obese group as compared to the nonobese group was determined using standard statistical methodologies. Results: For the 1687 patients in the database who met the blunt trauma inclusion criteria, measurements of the BMI and other information required for the study were available for only 657 of the subjects. The average age, male to female ratio and BMI were found to be very similar between the obese and nonobese groups (p Ͻ 0.05). Of these blunt trauma patients, 161 were determined to have a concurrent cervical spine injury. The statistically determined relative risk of sustaining a cervical spine injury for the obese patients was 0.67 as compared to the nonobese group. Conclusions: The relative risk of injury in obese patients who sustain blunt trauma has not been well characterized. This study suggests that obese patient have a lower risk of cervical spine injury as compared to their nonobese counterparts who are subjected to a similar severity of blunt trauma. One postulated explanation is that the cervical spine in obese patients is less mobile due to the abundance of subcutaneous fat and functions as an anatomic stabilizing factor. More study is necessary to clarify the influence of obesity on the incidence and mechanisms of traumatic injury.

Massive transfusion (MT) is associated with increased morbidity and mortality in severely injured... more Massive transfusion (MT) is associated with increased morbidity and mortality in severely injured patients. Early and aggressive use of blood products in these patients may correct coagulopathy, control bleeding, and improve outcomes. However, rapid identification of patients at risk for MT has been difficult. We postulated that evaluation of clinical variables routinely assessed upon admission would allow identification of these patients for earlier, more effective intervention. A retrospective cohort study was conducted at a single combat support hospital to identify risk factors for MT in patients with traumatic injuries. Demographic, diagnostic, and laboratory variables obtained upon admission were evaluated. Univariate and multivariate analyses were performed. An algorithm was formulated, validated with an independent dataset and a simple scoring system was devised. Three thousand four hundred forty-two patient records were reviewed. At least one unit of blood was transfused to 680 patients at the combat support hospital. Exclusion criteria included age less than 18 years, transfer from another medical facility, designation as a security internee, or incomplete data fields. The final number of patients was 302, of whom 26.5% (80 of 302) received a MT. Patients with MT had higher mortality (29 vs. 7% [p < 0.001]), and an increased Injury Severity Score (25 +/- 11.1 vs. 18 +/- 16.2 [p < 0.001]). Four independent risk factors for MT were identified: heart rate >105 bpm, systolic blood pressure <110 mm Hg, pH <7.25, and hematocrit…

Military Medicine

Introduction This study was conducted to identify and understand the current factors affecting re... more Introduction This study was conducted to identify and understand the current factors affecting recruitment, job satisfaction, and retention of U.S. Army Medical Corps officers and provide historical background to understand if the current factors are dissimilar. Materials and Methods An anonymous, voluntary questionnaire was sent to U.S. Army Medical Corps officers, and responses were tabulated and analyzed. Historical research was conducted and historical analysis applied. Results Recruiting, job satisfaction, and retention among Army Medical Corps Officers have been problematic throughout the 50-year history of the all-volunteer force. Recruiting has largely been of medical students, with very limited numbers of direct accessions. At times, satisfactory overall numbers have camouflaged shortages in key go-to-war specialties. Also, satisfactory numbers in a specialty have sometimes camouflaged problems in depth of experience. Satisfaction has been seen as a problem but apparently o...

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

Hemorrhage from extremity wounds is a leading cause of potentially preventable death during moder... more Hemorrhage from extremity wounds is a leading cause of potentially preventable death during modern combat operations. Optimal management involves rapid hemostasis and reversal of metabolic derangements utilizing damage control principles. The traditional practice of damage control surgery favors a life over limb approach and discourages elaborate, prolonged vascular reconstructions. We hypothesized that limb preservation could be successful when the damage control approach combines advanced resuscitative strategies and modern vascular techniques. Trauma Registry records at a Combat Support Hospital from April to June 2006 were retrospectively reviewed. Patients with life-threatening hemorrhage (defined as >4 units of packed red blood cells) who underwent simultaneous revascularization for a pulseless extremity were included. Data collection included the initial physiologic parameters in the emergency department (ED), total and 24-hour blood product requirements, and admission physiology and laboratory values in the intensive care unit (ICU). Outcome measures were survival, graft patency, and amputation rate at 7 days. Sixteen patients underwent 20 vascular reconstructions for upper (3) or lower extremity (17) wounds. Patients were hypotensive (blood pressure 105/60 +/- 29/18), acidotic (pH 7.27 +/- 0.1; BD -7.50 +/- 5.5), and coagulopathic (international normalized ratio 1.3 +/- 0.4) on arrival to the ED and essentially normal upon admission to the ICU, 4 hours later. Vein grafts (19/20, 95%) were used preferentially. Prosthetic grafts (1), shunting and delayed repair (4) or amputation (1) were infrequent. Heparin was not used or limited to a half dose (5/20, 25%). Tourniquets (12/16, 75%) and fasciotomies (13/16, 81%) were routine. Most (75%) received recombinant factor VIIa in the ED and in the operating room. All survived with normalized physiology on arrival in the ICU. Twenty-four-hour crystalloid use averaged 7.1 +/- 3.2 L, whereas packed red blood cells averaged 23 +/- 18 units, and 88% were massively transfused. Median operative time was 4.5 hours (range, 1.7-8.4 hours). Aggressive damage control resuscitation maneuvers in critically injured casualties successfully permitted prolonged, complex extremity revascularization with excellent early limb salvage and graft patency. Recombinant VIIa and liberal resuscitation with fresh whole blood, plasma, platelets and cryoprecipitate, while minimizing crystalloid, allowed limb salvage and did not result in early graft failures.

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

Objectives: Major vascular injury is a leading cause of potentially preventable hemorrhagic death... more Objectives: Major vascular injury is a leading cause of potentially preventable hemorrhagic death in modern combat operations. An optimal resuscitation approach for military trauma should offer both rapid hemorrhage control and early reversal of metabolic derangements. The objective of this report is to establish the use and effectiveness of a damage control resuscitation (DCR) strategy in the setting of wartime vascular injury.

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

(MT) is associated with increased morbidity and mortality in severely injured patients. Early and... more (MT) is associated with increased morbidity and mortality in severely injured patients. Early and aggressive use of blood products in these patients may correct coagulopathy, control bleeding, and improve outcomes. However, rapid identification of patients at risk for MT has been difficult. We postulated that evaluation of clinical variables routinely assessed upon admission would allow identification of these patients for earlier, more effective intervention.

The Journal of Trauma: Injury, Infection, and Critical Care, 2007

Current Surgery, 2002

The accurate nodal staging of colorectal cancer (CRC) is important to identify those patients who... more The accurate nodal staging of colorectal cancer (CRC) is important to identify those patients who may benefit from adjuvant chemotherapy. Some have suggested that identification of sentinel lymph nodes (SLN) may improve staging in CRC. We sought to determine: the feasibility of identifying SLN in CRC utilizing isosulfan blue dye; the accuracy of the identified SLN in predicting the status of the remainder of the lymph nodes in CRC; and whether a more thorough evaluation of SLN with serial step sectioning and immunohistochemistry would more accurately stage patients with CRC. A pilot trial was initiated at Walter Reed Army Medical Center (WRAMC), and 17 patients with masses on colonoscopy and subsequent tissue diagnosis of CRC were enrolled. Patients underwent standard surgical resection of their CRC with wedge of mesentery containing draining lymph nodes. Isosulfan blue dye was injected around the tumor subserosally/submucosally before dividing the mesenteric portion of the resection (n = 7) or ex vivo (n = 10). Sentinel lymph nodes were defined as all nodes staining blue and were dissected from the mesentery in the operating room. The SLN were sent separately for standard bivalving and hematoxylin and eosin staining (H&E) followed by serial step sectioning and immunohistochemistry (IHC) staining for cytokeratin. Seventeen patients (6 men, 11 women) were enrolled. The average preoperative carcinoembryonic antigen (CEA) was 5.9 (range, 1.2 to 18.9), and the average postoperative CEA was 2.8 (range, 0.7 to 9.1). One patient had a T1 tumor, 6 patients had T2 tumors, and 10 patients had T3 tumors on final pathology. Five cancers were well differentiated, 11 were moderately differentiated, and 1 was poorly differentiated. In all 17 cases, SLN were identified. A mean of 5.5 SLN was found per specimen (range, 2 to 11) with no difference noted between injection techniques (in vivo vs ex vivo). An additional 12 nonsentinel lymph nodes (range, 1 to 29) were identified per specimen. Ten patients had negative SLN and non-SLN. Seven patients were found to have positive SLN (3 by H&E, 2 by serial step sectioning, and 2 by IHC only). The isosulfan blue technique is technically feasible to allow identification of sentinel lymph nodes. In this study, no false-negative SLN occurred. A total of 7 patients had positive SLN; more importantly, 4 patients were upstaged as a result of serial step sectioning and immunohistochemistry staining. We hypothesize that this method may help pathologists find appropriate lymph nodes for more detailed analysis. As a result, patients may be more accurately staged and counseled for adjuvant chemotherapy, which has been shown to improve survival in node-positive CRC. Further studies should be undertaken to test these preliminary findings.

Arthritis & Rheumatism, 1995

To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blo... more To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc). Levels of the eosinophil-derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients. Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean +/- SD 762 +/- 271 ng/ml versus 534 +/- 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = -0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients. Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.

American Journal of Transplantation, 2002

Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytoki... more Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-a, TGF-b, and IFNg) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-g genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

Transplantation, 2001

Polymorphisms in the regulatory regions of cytokine genes affect protein production and are assoc... more Polymorphisms in the regulatory regions of cytokine genes affect protein production and are associated with allograft outcome. Ethnic origin has been identified as a significant prognostic factor for several immune-mediated diseases and for outcome after allotransplantation. A clear relationship between cytokine polymorphisms and ethnicity has not been shown. One hundred sixty subjects including 102 whites and 43 African-Americans were studied. Using polymerase chain reaction-based assays and, in some cases, restriction enzyme digestion, we determined genetic polymorphisms for the cytokines interleukin (IL) -2, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, and interferon-gamma (IFN-gamma). Genetic polymorphism frequencies were then compared to ethnicity using chi-square analysis and Fisher's exact two-tailed tests. For both the IL-2 and IL-6 genes, we found that whites and African-Americans differed significantly (P <0.05) in their allelic distribution and genotype frequency. A trend toward ethnic distribution was noted among the alleles and genotypes for the IL-10 and IFN-gamma genes. We found no correlation between ethnicity and either allelic distribution or genotype frequency for the tumor necrosis factor-alpha or transforming growth factor-beta genes. When comparisons were made between patients with or without a history of kidney failure, the allelic or genotypic distributions for the IL-6 and IFN-gamma genes were found to significantly differ. Our work demonstrates a correlation between ethnicity and polymorphisms in several cytokine genes. In addition, we found that patients requiring renal transplantation differ from the general population with regard to certain cytokine gene polymorphisms. These findings may have relevance in making prognostic determinations or tailoring immunomodulatory regimens after renal transplantation.

Transplantation, 2001

Genetic variations in cytokine genes are thought to regulate cytokine protein production. However... more Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described. We associated in vitro protein production with cytokine gene polymorphic genotypes after costimulation of cultured peripheral blood lymphocytes. PBL were isolated from forty healthy volunteers. Cytokine protein production was assessed by enzyme-linked immunosorbent assay. Polymorphisms in interleukin- (IL) 2, IL-6, IL-10, tumor necrosis factor (TNF-alpha), tumor growth factor (TGF-beta), and interferon (IFN-gamma) were determined by polymerase chain reaction (PCR). Statistical difference between protein production and cytokine polymorphic variants in the IL-10, IFN-gamma, and TNF-alpha genes was not evident after 48-hour stimulation with concanavalin-A. In contrast, after anti-CD3/CD28 stimulation significant differences (P<0.05) were found among high and low producers for IL-2, IL-6, and among high, intermediate, and low producers for IFN-gamma, and IL-10. Augmented levels of IL-2 in individuals that were homozygous for the polymorphic IL-2 allele were due to an early and sustained enhancement of IL-2 production. No association was found among TNF-alpha and TGF-beta genotypes and protein production. Polymorphisms in IL-2, IL-6, IL-10, and IFN-gamma genes are associated with their protein production after anti-CD3/CD28 stimulation. The profound effect of the IL-2 gene polymorphism in homozygous individuals may serve as a marker for those that could mount the most vigorous allo- or autoimmune responses, or perhaps become tolerant more easily.

The Journal of Trauma: Injury, Infection, and Critical Care, 2009

Military casualties with vascular injuries often present with severe acidosis and coagulopathy th... more Military casualties with vascular injuries often present with severe acidosis and coagulopathy that can negatively influence limb salvage decisions. We previously reported the value of a damage control resuscitation (DCR) strategy that can correct physiologic shock during simultaneous vascular reconstruction. The effect of recombinant factor VIIa (rFVIIa) on the repair of injured vessels and vascular grafts when used as an adjunctive therapy during DCR is unclear in the setting of wartime vascular injuries. The primary aim of this study was to assess the effect of rFVIIa use during DCR for vascular trauma and the impact on vessel repair. A retrospective two cohort case control study was performed using the Joint Theater Trauma Registry to identify patients with major vascular injury and DCR. Group 1 (n = 12) had DCR and repair of the injured vessels. Group 2 (n = 41) included early rFVIIa as an adjunctive therapy with DCR to control bleeding and perform simultaneous vascular reconstruction. Age, injury severity score, presenting physiology, and operative time were similar between groups. Postoperative data show that early physiologic recovery from acidosis, coagulopathy, and anemia was associated with rFVIIa and DCR. Extremity graft failures in groups 1 and 2 (follow-up range, 10-26 months) were either from early thrombosis (1 vs. 5 p = 1), graft dehiscence (1 vs. 2 p = 0.55), or infection (1 vs. 1 p = 0.41) and were the result of inadequate soft tissue coverage or technical factors that eventually resulted in eight (15%) amputations. All cause mortality (group 1: 0% vs. group 2: 7.3%, p = 1) and amputation rates (group 1: 25% vs. groups 2: 12.2%, p = 0.36) were similar between the two groups. DCR using rFVIIa is effective for controlling hemorrhage and reversing coagulopathy for severe vascular injuries. Early graft failures seem unrelated to rFVIIa use in the setting of wartime vascular injuries. No differences in amputation rate or mortality were seen. Although rFVIIa may be a useful damage control adjunct during vessel repair, the overall impact of this strategy on long-term outcomes such as mortality and limb salvage remains to be determined.

Journal of the American College of Surgeons, 2009

BACKGROUND: The incidence, survival, and blood product use after emergency department thoracotomy... more BACKGROUND: The incidence, survival, and blood product use after emergency department thoracotomy (EDT) in combat casualties is unknown. STUDY DESIGN: We performed a prospective and retrospective observational study of EDT at a combat support hospital in Iraq, evaluating the impact of injury mechanisms, blood product use, mortality, and longterm neurologic outcomes of survivors.

CHEST Journal, 2004

INTRODUCTION: The role of surgical management in T4 non-small cell lung cancer (NSCLC) remains co... more INTRODUCTION: The role of surgical management in T4 non-small cell lung cancer (NSCLC) remains controversial. Treatment is usually palliative, yet a certain proportion of patients may benefit from curative treatment. We report on radical en bloc resection of a right upper lobe (RUL) NSCLC invading the 3rd and 4th thoracic vertebrae. CASE PRESENTATION: A 51-year-old white male smoker developed right shoulder and upper back pain. Initial conservative management failed to resolve the pain. Plain films revealed degenerative joint disease. The pain persisted. Computed tomography (CT) and magnetic resonance imaging showed a 5 x 5.1 cm RUL mass invading the right T3-T4 neural foramen and a portion of the T2 vertebral body. CT-guided biopsy revealed squamous cell carcinoma, and mediastinoscopy was negative for N2 disease. Clinical stage was T4N0M0 (Stage IIIB) NSCLC. After neoadjuvant therapy (Taxol/Cisplatin and 5000 cGy), a Neotec scan revealed no evidence of distant disease. Pulmonary function tests were normal. Repeat imaging studies showed no evidence of cord compression and partial tumor response. The patient was taken to the operating room where he underwent radical en bloc resection of the tumor, which included a right upper lobectomy, chest wall and three level vertebrectomy. Spinal integrity was achieved by anterior cage reconstruction followed by posterior rod stabilization. A complete resection was achieved histologically. Three years later, he is well, without radiologic or clinical evidence of recurrence. DISCUSSIONS: Surgery remains the 'gold standard' for early-stage lung cancer. Stage IIIB NSCLC is considered an inoperable disease; however, Stage IIIB represents a heterogeneous group of patients, including the subgroup of T4N0M0 patients. These patients may benefit from an aggressive surgical approach, oftentimes after neoadjuvant therapy. Several authors have described acceptable outcomes after surgical treatment. DeMeester, et al (1) reported 12 patients with T4N0M0 NSCLC with tumor adherent to the vertebral column who underwent preoperative radiotherapy and radical surgical excision with a 5-year Kaplan-Meier survival of 42%. Grunenwald et al (2) demonstrated a 14% predicted 5-year survival in 19 patients undergoing en bloc partial and total vertebrectomy for lung cancer invading the spine. Other authors (34567) have reported 5-year survival rates ranging from 10-28% in a heterogeneous group of T4 lung cancer patients. Operative morbidity and mortality have been acceptable in this high-risk group of patients. Factors contributing to long-term survival appear to include response to neoadjuvant therapy, ability to achieve complete histologic resection, and absence of N2 or N3 nodal disease. CONCLUSION: The role of surgery for Stage IIIB NSCLC remains controversial. Various authors have advocated surgical therapy for certain subsets of Stage IIIB NSCLC. We present a case of T4N0M0 NSCLC invading several levels of the thoracic vertebrae. Aggressive en bloc surgical resection and reconstruction after neoadjuvant therapy resulted in a negative margin resection and long-term survival.

Annals of Emergency Medicine, 2007

Annals of Emergency Medicine, 2008

Study Objectives: The incidence of obesity has reached epidemic proportions in the United States.... more Study Objectives: The incidence of obesity has reached epidemic proportions in the United States. The impact of this comorbid condition on the likelihood of injury in the trauma patient is unknown. In this study, the relative risk of cervical spine injury was determined for a population of obese blunt trauma patients as compared to a nonobese cohort. Methods: A retrospective analysis of an electronic patient database at a Level 1 trauma center with a large referral base of patients with cervical spine injuries was conducted for the period from September 1, 2005 to December 31, 2007. In addition to standard demographic characteristics, information with regard to cervical spine injury and body mass index (BMI) were collected for each patient with blunt trauma who met the criteria for a trauma activation or trauma consultation due to significant injury. The patients were then divided into the categories of obese and nonobese based on the World Health Organization classification (BMI cutoff of 30). The relative risk of cervical spine injury in the obese group as compared to the nonobese group was determined using standard statistical methodologies. Results: For the 1687 patients in the database who met the blunt trauma inclusion criteria, measurements of the BMI and other information required for the study were available for only 657 of the subjects. The average age, male to female ratio and BMI were found to be very similar between the obese and nonobese groups (p Ͻ 0.05). Of these blunt trauma patients, 161 were determined to have a concurrent cervical spine injury. The statistically determined relative risk of sustaining a cervical spine injury for the obese patients was 0.67 as compared to the nonobese group. Conclusions: The relative risk of injury in obese patients who sustain blunt trauma has not been well characterized. This study suggests that obese patient have a lower risk of cervical spine injury as compared to their nonobese counterparts who are subjected to a similar severity of blunt trauma. One postulated explanation is that the cervical spine in obese patients is less mobile due to the abundance of subcutaneous fat and functions as an anatomic stabilizing factor. More study is necessary to clarify the influence of obesity on the incidence and mechanisms of traumatic injury.

Massive transfusion (MT) is associated with increased morbidity and mortality in severely injured... more Massive transfusion (MT) is associated with increased morbidity and mortality in severely injured patients. Early and aggressive use of blood products in these patients may correct coagulopathy, control bleeding, and improve outcomes. However, rapid identification of patients at risk for MT has been difficult. We postulated that evaluation of clinical variables routinely assessed upon admission would allow identification of these patients for earlier, more effective intervention. A retrospective cohort study was conducted at a single combat support hospital to identify risk factors for MT in patients with traumatic injuries. Demographic, diagnostic, and laboratory variables obtained upon admission were evaluated. Univariate and multivariate analyses were performed. An algorithm was formulated, validated with an independent dataset and a simple scoring system was devised. Three thousand four hundred forty-two patient records were reviewed. At least one unit of blood was transfused to 680 patients at the combat support hospital. Exclusion criteria included age less than 18 years, transfer from another medical facility, designation as a security internee, or incomplete data fields. The final number of patients was 302, of whom 26.5% (80 of 302) received a MT. Patients with MT had higher mortality (29 vs. 7% [p < 0.001]), and an increased Injury Severity Score (25 +/- 11.1 vs. 18 +/- 16.2 [p < 0.001]). Four independent risk factors for MT were identified: heart rate >105 bpm, systolic blood pressure <110 mm Hg, pH <7.25, and hematocrit…

Military Medicine

Introduction This study was conducted to identify and understand the current factors affecting re... more Introduction This study was conducted to identify and understand the current factors affecting recruitment, job satisfaction, and retention of U.S. Army Medical Corps officers and provide historical background to understand if the current factors are dissimilar. Materials and Methods An anonymous, voluntary questionnaire was sent to U.S. Army Medical Corps officers, and responses were tabulated and analyzed. Historical research was conducted and historical analysis applied. Results Recruiting, job satisfaction, and retention among Army Medical Corps Officers have been problematic throughout the 50-year history of the all-volunteer force. Recruiting has largely been of medical students, with very limited numbers of direct accessions. At times, satisfactory overall numbers have camouflaged shortages in key go-to-war specialties. Also, satisfactory numbers in a specialty have sometimes camouflaged problems in depth of experience. Satisfaction has been seen as a problem but apparently o...

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

Hemorrhage from extremity wounds is a leading cause of potentially preventable death during moder... more Hemorrhage from extremity wounds is a leading cause of potentially preventable death during modern combat operations. Optimal management involves rapid hemostasis and reversal of metabolic derangements utilizing damage control principles. The traditional practice of damage control surgery favors a life over limb approach and discourages elaborate, prolonged vascular reconstructions. We hypothesized that limb preservation could be successful when the damage control approach combines advanced resuscitative strategies and modern vascular techniques. Trauma Registry records at a Combat Support Hospital from April to June 2006 were retrospectively reviewed. Patients with life-threatening hemorrhage (defined as >4 units of packed red blood cells) who underwent simultaneous revascularization for a pulseless extremity were included. Data collection included the initial physiologic parameters in the emergency department (ED), total and 24-hour blood product requirements, and admission physiology and laboratory values in the intensive care unit (ICU). Outcome measures were survival, graft patency, and amputation rate at 7 days. Sixteen patients underwent 20 vascular reconstructions for upper (3) or lower extremity (17) wounds. Patients were hypotensive (blood pressure 105/60 +/- 29/18), acidotic (pH 7.27 +/- 0.1; BD -7.50 +/- 5.5), and coagulopathic (international normalized ratio 1.3 +/- 0.4) on arrival to the ED and essentially normal upon admission to the ICU, 4 hours later. Vein grafts (19/20, 95%) were used preferentially. Prosthetic grafts (1), shunting and delayed repair (4) or amputation (1) were infrequent. Heparin was not used or limited to a half dose (5/20, 25%). Tourniquets (12/16, 75%) and fasciotomies (13/16, 81%) were routine. Most (75%) received recombinant factor VIIa in the ED and in the operating room. All survived with normalized physiology on arrival in the ICU. Twenty-four-hour crystalloid use averaged 7.1 +/- 3.2 L, whereas packed red blood cells averaged 23 +/- 18 units, and 88% were massively transfused. Median operative time was 4.5 hours (range, 1.7-8.4 hours). Aggressive damage control resuscitation maneuvers in critically injured casualties successfully permitted prolonged, complex extremity revascularization with excellent early limb salvage and graft patency. Recombinant VIIa and liberal resuscitation with fresh whole blood, plasma, platelets and cryoprecipitate, while minimizing crystalloid, allowed limb salvage and did not result in early graft failures.

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

Objectives: Major vascular injury is a leading cause of potentially preventable hemorrhagic death... more Objectives: Major vascular injury is a leading cause of potentially preventable hemorrhagic death in modern combat operations. An optimal resuscitation approach for military trauma should offer both rapid hemorrhage control and early reversal of metabolic derangements. The objective of this report is to establish the use and effectiveness of a damage control resuscitation (DCR) strategy in the setting of wartime vascular injury.

The Journal of Trauma: Injury, Infection, and Critical Care, 2008

(MT) is associated with increased morbidity and mortality in severely injured patients. Early and... more (MT) is associated with increased morbidity and mortality in severely injured patients. Early and aggressive use of blood products in these patients may correct coagulopathy, control bleeding, and improve outcomes. However, rapid identification of patients at risk for MT has been difficult. We postulated that evaluation of clinical variables routinely assessed upon admission would allow identification of these patients for earlier, more effective intervention.

The Journal of Trauma: Injury, Infection, and Critical Care, 2007

Current Surgery, 2002

The accurate nodal staging of colorectal cancer (CRC) is important to identify those patients who... more The accurate nodal staging of colorectal cancer (CRC) is important to identify those patients who may benefit from adjuvant chemotherapy. Some have suggested that identification of sentinel lymph nodes (SLN) may improve staging in CRC. We sought to determine: the feasibility of identifying SLN in CRC utilizing isosulfan blue dye; the accuracy of the identified SLN in predicting the status of the remainder of the lymph nodes in CRC; and whether a more thorough evaluation of SLN with serial step sectioning and immunohistochemistry would more accurately stage patients with CRC. A pilot trial was initiated at Walter Reed Army Medical Center (WRAMC), and 17 patients with masses on colonoscopy and subsequent tissue diagnosis of CRC were enrolled. Patients underwent standard surgical resection of their CRC with wedge of mesentery containing draining lymph nodes. Isosulfan blue dye was injected around the tumor subserosally/submucosally before dividing the mesenteric portion of the resection (n = 7) or ex vivo (n = 10). Sentinel lymph nodes were defined as all nodes staining blue and were dissected from the mesentery in the operating room. The SLN were sent separately for standard bivalving and hematoxylin and eosin staining (H&E) followed by serial step sectioning and immunohistochemistry (IHC) staining for cytokeratin. Seventeen patients (6 men, 11 women) were enrolled. The average preoperative carcinoembryonic antigen (CEA) was 5.9 (range, 1.2 to 18.9), and the average postoperative CEA was 2.8 (range, 0.7 to 9.1). One patient had a T1 tumor, 6 patients had T2 tumors, and 10 patients had T3 tumors on final pathology. Five cancers were well differentiated, 11 were moderately differentiated, and 1 was poorly differentiated. In all 17 cases, SLN were identified. A mean of 5.5 SLN was found per specimen (range, 2 to 11) with no difference noted between injection techniques (in vivo vs ex vivo). An additional 12 nonsentinel lymph nodes (range, 1 to 29) were identified per specimen. Ten patients had negative SLN and non-SLN. Seven patients were found to have positive SLN (3 by H&E, 2 by serial step sectioning, and 2 by IHC only). The isosulfan blue technique is technically feasible to allow identification of sentinel lymph nodes. In this study, no false-negative SLN occurred. A total of 7 patients had positive SLN; more importantly, 4 patients were upstaged as a result of serial step sectioning and immunohistochemistry staining. We hypothesize that this method may help pathologists find appropriate lymph nodes for more detailed analysis. As a result, patients may be more accurately staged and counseled for adjuvant chemotherapy, which has been shown to improve survival in node-positive CRC. Further studies should be undertaken to test these preliminary findings.

Arthritis & Rheumatism, 1995

To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blo... more To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc). Levels of the eosinophil-derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients. Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean +/- SD 762 +/- 271 ng/ml versus 534 +/- 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = -0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients. Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.

American Journal of Transplantation, 2002

Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytoki... more Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-a, TGF-b, and IFNg) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-g genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

Transplantation, 2001

Polymorphisms in the regulatory regions of cytokine genes affect protein production and are assoc... more Polymorphisms in the regulatory regions of cytokine genes affect protein production and are associated with allograft outcome. Ethnic origin has been identified as a significant prognostic factor for several immune-mediated diseases and for outcome after allotransplantation. A clear relationship between cytokine polymorphisms and ethnicity has not been shown. One hundred sixty subjects including 102 whites and 43 African-Americans were studied. Using polymerase chain reaction-based assays and, in some cases, restriction enzyme digestion, we determined genetic polymorphisms for the cytokines interleukin (IL) -2, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, and interferon-gamma (IFN-gamma). Genetic polymorphism frequencies were then compared to ethnicity using chi-square analysis and Fisher's exact two-tailed tests. For both the IL-2 and IL-6 genes, we found that whites and African-Americans differed significantly (P <0.05) in their allelic distribution and genotype frequency. A trend toward ethnic distribution was noted among the alleles and genotypes for the IL-10 and IFN-gamma genes. We found no correlation between ethnicity and either allelic distribution or genotype frequency for the tumor necrosis factor-alpha or transforming growth factor-beta genes. When comparisons were made between patients with or without a history of kidney failure, the allelic or genotypic distributions for the IL-6 and IFN-gamma genes were found to significantly differ. Our work demonstrates a correlation between ethnicity and polymorphisms in several cytokine genes. In addition, we found that patients requiring renal transplantation differ from the general population with regard to certain cytokine gene polymorphisms. These findings may have relevance in making prognostic determinations or tailoring immunomodulatory regimens after renal transplantation.

Transplantation, 2001

Genetic variations in cytokine genes are thought to regulate cytokine protein production. However... more Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described. We associated in vitro protein production with cytokine gene polymorphic genotypes after costimulation of cultured peripheral blood lymphocytes. PBL were isolated from forty healthy volunteers. Cytokine protein production was assessed by enzyme-linked immunosorbent assay. Polymorphisms in interleukin- (IL) 2, IL-6, IL-10, tumor necrosis factor (TNF-alpha), tumor growth factor (TGF-beta), and interferon (IFN-gamma) were determined by polymerase chain reaction (PCR). Statistical difference between protein production and cytokine polymorphic variants in the IL-10, IFN-gamma, and TNF-alpha genes was not evident after 48-hour stimulation with concanavalin-A. In contrast, after anti-CD3/CD28 stimulation significant differences (P<0.05) were found among high and low producers for IL-2, IL-6, and among high, intermediate, and low producers for IFN-gamma, and IL-10. Augmented levels of IL-2 in individuals that were homozygous for the polymorphic IL-2 allele were due to an early and sustained enhancement of IL-2 production. No association was found among TNF-alpha and TGF-beta genotypes and protein production. Polymorphisms in IL-2, IL-6, IL-10, and IFN-gamma genes are associated with their protein production after anti-CD3/CD28 stimulation. The profound effect of the IL-2 gene polymorphism in homozygous individuals may serve as a marker for those that could mount the most vigorous allo- or autoimmune responses, or perhaps become tolerant more easily.

The Journal of Trauma: Injury, Infection, and Critical Care, 2009

Military casualties with vascular injuries often present with severe acidosis and coagulopathy th... more Military casualties with vascular injuries often present with severe acidosis and coagulopathy that can negatively influence limb salvage decisions. We previously reported the value of a damage control resuscitation (DCR) strategy that can correct physiologic shock during simultaneous vascular reconstruction. The effect of recombinant factor VIIa (rFVIIa) on the repair of injured vessels and vascular grafts when used as an adjunctive therapy during DCR is unclear in the setting of wartime vascular injuries. The primary aim of this study was to assess the effect of rFVIIa use during DCR for vascular trauma and the impact on vessel repair. A retrospective two cohort case control study was performed using the Joint Theater Trauma Registry to identify patients with major vascular injury and DCR. Group 1 (n = 12) had DCR and repair of the injured vessels. Group 2 (n = 41) included early rFVIIa as an adjunctive therapy with DCR to control bleeding and perform simultaneous vascular reconstruction. Age, injury severity score, presenting physiology, and operative time were similar between groups. Postoperative data show that early physiologic recovery from acidosis, coagulopathy, and anemia was associated with rFVIIa and DCR. Extremity graft failures in groups 1 and 2 (follow-up range, 10-26 months) were either from early thrombosis (1 vs. 5 p = 1), graft dehiscence (1 vs. 2 p = 0.55), or infection (1 vs. 1 p = 0.41) and were the result of inadequate soft tissue coverage or technical factors that eventually resulted in eight (15%) amputations. All cause mortality (group 1: 0% vs. group 2: 7.3%, p = 1) and amputation rates (group 1: 25% vs. groups 2: 12.2%, p = 0.36) were similar between the two groups. DCR using rFVIIa is effective for controlling hemorrhage and reversing coagulopathy for severe vascular injuries. Early graft failures seem unrelated to rFVIIa use in the setting of wartime vascular injuries. No differences in amputation rate or mortality were seen. Although rFVIIa may be a useful damage control adjunct during vessel repair, the overall impact of this strategy on long-term outcomes such as mortality and limb salvage remains to be determined.

Journal of the American College of Surgeons, 2009

BACKGROUND: The incidence, survival, and blood product use after emergency department thoracotomy... more BACKGROUND: The incidence, survival, and blood product use after emergency department thoracotomy (EDT) in combat casualties is unknown. STUDY DESIGN: We performed a prospective and retrospective observational study of EDT at a combat support hospital in Iraq, evaluating the impact of injury mechanisms, blood product use, mortality, and longterm neurologic outcomes of survivors.