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African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P

Data from the trauma patient population suggests handsewn (HS) anastomoses are superior to stapled (ST). A recent retrospective study in emergency general surgery (EGS) patients had similar findings. The aim of the current study was to evaluate HS and ST anastomoses in EGS patients undergoing urgent/emergent operations.The study was sponsored by the American Association for the Surgery of Trauma Multi-Institutional Studies Committee. Patients undergoing urgent/emergent bowel resection for EGS pathology were prospectively enrolled from July 22, 2013 to December 31, 2015. Patients were grouped by HS/ST anastomoses, and variables were collected. The primary outcome was anastomotic failure. Similar to other studies, anastomotic failure was evaluated at the anastomosis level. Multivariable logistic regression was performed controlling for age and risk factors for anastomotic failure.Fifteen institutions enrolled a total of 595 patients with 649 anastomoses (253 HS and 396 ST). Mean age was 61 years, 51% were men, 7% overall mortality. Age and sex were the same between groups. The overall anastomotic failure rate was 12.5%. The HS group had higher lactate, lower albumin, and were more likely to be on vasopressors. Hospital and intensive care unit days, as well as mortality, were greater in the HS group. Anastomotic failure rates and operative time were equivalent for HS and ST. On multivariate regression, the presence of contamination at initial resection (odds ratio, 1.965; 95% confidence interval, 1.183-3.264) and the patient being managed with open abdomen (odds ratio, 2.529; 95% confidence interval, 1.492-4.286) were independently associated with anastomotic failure, while the type of anastomosis was not.EGS patients requiring bowel resection and anastomosis are at high risk for anastomotic failure. The current study illustrates an apparent bias among acute care surgeons to perform HS techniques in higher-risk patients. Despite the individualized application of technique for differing patient populations, the risk of anastomotic failure was equivalent when comparing HS and ST anastomoses.Therapeutic study, level II.

BackgroundThoracic injuries are common in trauma. Approximately one-third will develop a pneumothorax, hemothorax, or hemopneumothorax (HPTX), usually with concomitant rib fractures. Tube thoracostomy (TT) is the standard of care for these conditions, though TTs expose the patient to the risk of infectious complications. The controversy regarding antibiotic prophylaxis at the time of TT placement remains unresolved. This multicenter study sought to reconcile divergent evidence regarding the effectiveness of antibiotics given as prophylaxis with TT placement.MethodsThe primary outcome measures of in-hospital empyema and pneumonia were evaluated in this prospective, observational, and American Association for the Surgery of Trauma multicenter study. Patients were grouped according to treatment status (ABX and NoABX). A 1:1 nearest neighbor method matched the ABX patients with NoABX controls. Multilevel models with random effects for matched pairs and trauma centers were fit for binary and count outcomes using logistic and negative binomial regression models, respectively.ResultsTTs for HPTX were placed in 1887 patients among 23 trauma centers. The ABX and NoABX groups accounted for 14% and 86% of the patients, respectively. Cefazolin was the most frequent of 14 antibiotics prescribed. No difference in the incidence of pneumonia and empyema was observed between groups (2.2% vs 1.5%, p=0.75). Antibiotic treatment demonstrated a positive but non-significant association with risk of pneumonia (OR 1.61; 95% CI: 0.86~3.03; p=0.14) or empyema (OR 1.51; 95% CI: 0.42~5.42; p=0.53).ConclusionThere is no evidence to support the routine use of presumptive antibiotics for post-traumatic TT to decrease the incidence of pneumonia or empyema. More investigation is necessary to balance optimal patient outcomes and antibiotic stewardship.Level of evidenceII Prospective comparative study

Aortic occlusion (AO) for resuscitation in traumatic shock remains controversial. Resuscitative endovascular balloon occlusion of the aorta (REBOA) offers an emerging alternative.The American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry prospectively identified trauma patients requiring AO from eight ACS Level 1 centers. Presentation, intervention, and outcome variables were collected and analyzed to compare REBOA and open AO.From November 2013 to February 2015, 114 AO patients were captured (REBOA, 46; open AO, 68); 80.7% were male, and 62.3% were blunt injured. Aortic occlusion occurred in the emergency department (73.7%) or the operating room (26.3%). Hemodynamic improvement after AO was observed in 62.3% [REBOA, 67.4%; open OA, 61.8%); 36.0% achieving stability (systolic blood pressure consistently90 mm Hg,5 minutes); REBOA, 22 of 46 (47.8%); open OA, 19 of 68 (27.9%); p =0.014]. Resuscitative endovascular balloon occlusion of the aorta (REBOA) access was femoral cut-down (50%); US guided (10.9%) and percutaneous without imaging (28.3%). Deployment was achieved in Zones I (78.6%), II (2.4%), and III (19.0%). A second AO attempt was required in 9.6% [REBOA, 2 of 46 (4.3%); open OA, 9 of 68 (13.2%)]. Complications of REBOA were uncommon (pseudoaneurysm, 2.1%; embolism, 4.3%; limb ischemia, 0%). There was no difference in time to successful AO between REBOA and open procedures (REBOA, 6.6 ± 5.6 minutes; open OA, 7.2 ± 15.1; p = 0.842). Overall survival was 21.1% (24 of 114), with no significant difference between REBOA and open AO with regard to mortality [REBOA, 28.2% (13 of 46); open OA, 16.1% (11 of 68); p = 0.120].Resuscitative endovascular balloon occlusion of the aorta has emerged as a viable alternative to open AO in centers that have developed this capability. Further maturation of the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery database is required to better elucidate optimal indications and outcomes.Therapeutic/care management study, level IV.

Traumatic brain injuries (TBI) are among the most misdiagnosed and underreported types of head trauma. The potential long-term impact of undiagnosed or incorrectly identified concussions and other head injuries are potentially devastating, as evidenced by the increasing societal burden exhibited by soldiers returning from combat and athletes in contact sports. Concussions and TBI are notoriously difficult to correctly diagnose and prognosis for these injuries is poorly understood. In order to increase the likelihood of successful diagnosis, treatment, and prediction of outcomes, a definitive differential diagnosis will need to be established. The establishment of a "trauma-specific profile" or a panel of known trauma markers will significantly aid in this goal. Small membrane vesicles called exosomes have been shown to contain proteins and injury-specific biomarkers. In the future it is possible that they could become an important tool, utilized for their diagnostic and therapeutic potential.

Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations.

African-American men have the highest rate of prostate cancer (PCa) incidence in the U.S. In addition, their prostate cancer mortality rate is more than twice as high as the rate for white Americans. The causes of higher rates of prostate cancer among African-American males are largely unknown. Many studies are underway to unravel the impact of a wide variety of potential risk factors, including dietary and other lifestyle differences, occupational exposures, hormonal and genetic differences. Several lines of evidence suggest that one of the main events associated with the conversion to an aggressive phenotype is increased resistance to apoptosis (3) mainly due to upregulation of antiapoptotic genes, including Bcl-2, Bcl-XL, Mcl-1, and Survivin. Recently, we reported that Survivin is released in PCa sera and found to be in the exosomes. Therefore, we speculate that Survivin could be a potential target protein released differentially in prostate cancers in African American (AA) and Caucasian (CC) populations in response to stress. In this study, we have collected serum samples from prostate cancer patients of AA and CC, measured Survivin levels by ELISA. Exosome islation was perfomed by Exoquick approach and quantified by acetylcholinesterase activity assays. We have applied an in-vitro approach to compare the differences between cancer cell lines derived from AA (MDA-MB-PCa) and CC (PC3) patients in terms of stress and stress activated Survivin release by exosomes. Under oxidative stress and drug treatments, we have identified Survivin highly expressed in exosome derived from MDA-MB-PCa compared to PC3 cell lines. In addition, we found a relative overexpression of Survivin protein in AA-PCa compared to CC-PCa both in sera and exosomes. Based on our data, Survivin may be a key stress-induced protein in AA-PCa patients. It is possible that attempts to block Survivin release will not only interrupt the cancer proliferation and interfere with anti-apoptotic pathways, thus preventing cancer progression. Citation Format: Salma Khan, David Turay, Jessica Ms Jutzy, Jonathan R. Aspe, Tino W. Sanchez, Saeid Mirshahidi, Carlos A. Casiano, Nathan R. Wall. Stress-induced differential Survivin release in prostate cancer health disparities. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1118. doi:10.1158/1538-7445.AM2014-1118

Background The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues. Our previous work showed Survivin is released from tumor cells via small membrane-bound vesicles called exosomes. We, therefore, hypothesize that analysis of serum exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer. Methods We collected sera from forty breast cancer patients and ten control patients who were disease free for 5 years after treatment. In addition, twenty-three paired breast cancer tumor tissues from those same 40 patients were analyzed for splice variants. Serum levels of Survivin were analyzed using ELISA and exosomes were isolated from this serum using the commercially available ExoQuick kit, with subsequent Western blots and immunohistochemistry performed. Results Survivin levels were significantly higher in all the breast cancer samples compared to controls (p Conclusion In this study we show for the first time that like Survivin, the Survivin splice variants are also exosomally packaged in the breast cancer patients’ sera, mimicking the survivin splice variant pattern that we also report in breast cancer tissues. Differential expression of exosomal-Survivin, particularly Survivin-2B, may serve as a diagnostic and/or prognostic marker, a “liquid biopsy” if you will, in early breast cancer patients. Furthermore, a more thorough understanding of the role of this prominent antiapoptotic pathway could lead to the development of potential therapeutics for breast cancer patients.

Background Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. Methods Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. Results Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. Conclusions These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.

35 Background: The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues and have recently been shown to be released from tumor cells via small membrane-bound vesicles called exosomes. Tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions by impacting immune escape, tumor invasion and angiogenesis. We, therefore, hypothesize that analysis of exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer in addition to current recommended methods. Methods: Twenty paired breast cancer patient’s sera and tumor tissue, and ten normal control sera were used for analysis. ELISA was performed to quantitate serum levels of Survivin. Exosomes were isolated from the sera using Exoquick. RT-PCR, western blots with densitometry, and immunohistochemistry followed by confocal microscopy were then performed. Results: For each breast cancer patient serum, Survivin levels were significantly higher compared to control (p