Explore the vast range of titles available.

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<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

Background The traditional sequence of trauma care: Airway, Breathing, Circulation (ABC) has been practiced for many years. It became the standard of care despite the lack of scientific evidence. We hypothesized that patients in hypovolemic shock would have comparable outcomes with initiation of bleeding treatment (transfusion) prior to intubation (CAB), compared to those patients treated with the traditional ABC sequence. Methods This study was sponsored by the American Association for the Surgery of Trauma multicenter trials committee. We performed a retrospective analysis of all patients that presented to trauma centers with presumptive hypovolemic shock indicated by pre-hospital or emergency department hypotension and need for intubation from January 1, 2014 to July 1, 2016. Data collected included demographics, timing of intubation, vital signs before and after intubation, timing of the blood transfusion initiation related to intubation, and outcomes. Results From 440 patients that met inclusion criteria, 245 (55.7%) received intravenous blood product resuscitation first (CAB), and 195 (44.3%) were intubated before any resuscitation was started (ABC). There was no difference in ISS, mechanism, or comorbidities. Those intubated prior to receiving transfusion had a lower GCS than those with transfusion initiation prior to intubation (ABC: 4, CAB:9, p  = 0.005). Although mortality was high in both groups, there was no statistically significant difference (CAB 47% and ABC 50%). In multivariate analysis, initial SBP and initial GCS were the only independent predictors of death. Conclusion The current study highlights that many trauma centers are already initiating circulation first prior to intubation when treating hypovolemic shock (CAB), even in patients with a low GCS. This practice was not associated with an increased mortality. Further prospective investigation is warranted. Trial registration IRB approval number: HM20006627. Retrospective trial not registered.

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. 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. 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. 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.

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 < 0.05) with exosome amounts significantly higher in cancer patient sera compared to controls (p < 0.01). While Survivin and Survivin-∆Ex3 splice variant expression and localization was identical in serum exosomes, differential expression of Survivin-2B protein existed in the exosomes. Similarly, Survivin and Survivin-∆Ex3 proteins were the predominant forms detected in all of the breast cancer tissues evaluated in this study, whereas a more variable expression of Survivin-2B level was found at different cancer stages. 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 There are limited studies regarding the impact of post-operative leak on perforated peptic ulcer disease (PPUD) and conflicting results regarding routine drain placement in operative repair of PPUD. This study aims to identify risk factors for gastrointestinal leak after operative repair of PPUD to better guide intra-operative decisions about drain placement. Methods We performed a retrospective cohort study at a tertiary care center from 2008 to 2019, identifying 175 patients who underwent operative repair of PPUD. Results Patients who developed a leak (17%) were compared to patients who did not. Both hypoalbuminemia (albumin < 3.5 g/dL) (P = .03) and duodenal ulcers (P < .01) were identified as significant risk factors for leak. No significant difference was found between leak and no leak groups for AAST disease severity grade, repair technique, or pre-operative use of tobacco, alcohol, or steroids. Post-operative leaks were associated with prolonged hospital stay (29 days compared to 10, P < .01), increased complication rates (77% compared to 48%, P < .01), and increased re-operation rates (73% compared to 26%, <0.01). No difference was identified in patient characteristics or operative leak rates between patients who had drains placed at the index operation and those that did not. Discussion Leak after operative PPUD repair is associated with significant post-operative morbidity. Hypoalbuminemia and duodenal perforations are significant risk factors for post-operative leaks.

Estimating the prevalence of harassment, verbal abuse, and discrimination among residents is difficult as events are often under-reported. The purpose of this study was to determine the prevalence of discrimination and abuse among surgical residents using the HITS (Hurt, Insulted, Threatened with harm or Screamed at) screening tool. A multicenter, cross-sectional, survey-based study was conducted at five academic teaching hospitals. Of 310 residents, 76 (24.5%) completed the survey. The HITS screening tool was positive in 3.9 per cent. The most common forms of abuse included sexual harassment (28.9%), discrimination based on gender (15.7%), and discrimination based on ethnicity (7.9%). There was a positive correlation between individuals who reported gender discrimination and racial discrimination (r = 0.778, n = 13, P = 0.002). Individuals who experienced insults were more likely to experience physical threats (r = 0.437, n = 79, P < 0.001) or verbal abuse (r = 0.690, n = 79, P < 0.001). Discrimination and harassment among surgical residents in academic teaching hospitals across the United States is not uncommon. Further research is needed to determine the impact of these findings on resident attrition.

PurposeSedation management of trauma patients after damage control laparotomy (DCL) has not been optimized. We evaluated if shorter sedation exposure was associated with increased proportion of delirium-free/coma-free (DF/CF-ICU) days and change in time to definitive fascial closure (DFC).MethodsWe reviewed trauma DCL patients at an ACS-verified level I center over 5 years as shorter (SE) or longer than median (LE) sedation exposure. We compared demographics, injury patterns, hemodynamic parameters, and injury severity between groups. We calculated the propensity for each patient to achieve DFC using age, gender, ISS, red blood cell transfusion, bowel discontinuity, abdominal vascular injury, and time to first takeback; we then determined the effect of sedation exposure on rate of DFC by multivariate Cox regression, adjusted for propensity to achieve DFC. We used linear regression adjusted for age, ISS, head-AIS, bowel discontinuity, and vascular injury to determine the effect of sedation exposure on the proportion of DF/CF-ICU days.Results65 patients (33.8% penetrating) had mean age 41.8 ± 16.0, ISS 27.1 ± 14.2, Head-AIS 1.2 ± 1.6 and median sedation exposure of 2.2 [IQR 0.78, 7.3] days (35 SE and 30 LE). Pattern and severity of solid organ injuries and proportion of small and large bowel and vascular injuries were similar between groups. LE had more abdominal sepsis (23.3% vs 0%, p = 0.003) and enterocutaneous fistula (16.7% vs 0%, p = 0.016), and more ventilator (17.3 ± 12.7 vs 6.1 ± 6.8, p < 0.001), ICU (20.8 ± 14.2 vs 7.2 ± 7.6, p < 0.001), and hospital days (29.6 ± 19.6 vs 13.9 ± 9.0, p < 0.001). DFC was achieved more rapidly in the SE group (2.0 ± 1.5 days vs 3.9 ± 3.7 days [unadjusted], p = 0.023) and SE had a higher proportion of unadjusted DF/CF-ICU days (33.0 ± 32.0% vs 18.1 ± 16.4%, p = 0.020).SE was associated with an increased proportion of adjusted DF/CF-ICU days by multivariate linear regression (13.1% [95% CI 1.4–24.8%], p = 0.029) and with faster adjusted rate of DFC by multivariate Cox regression (RR 2.28 [95% CI 1.25–4.15, p = 0.007]).ConclusionsShorter sedation exposure is associated with increased proportion of DF/CF-ICU days and more rapid DFC after DCL for trauma.

We sought to evaluate whether the Emergency Surgery Score (ESS) can accurately predict outcomes in elderly patients undergoing emergent laparotomy (EL). This is a post-hoc analysis of an EAST multicenter study. Between April 2018 and June 2019, all adult patients undergoing EL in 19 participating hospitals were prospectively enrolled, and ESS was calculated for each patient. Using the c-statistic, the correlation between ESS and mortality, morbidity, and need for ICU admission was assessed in three patient age cohorts (65–74, 75–84, ≥85 years old). 715 patients were included, of which 52% were 65–74, 34% were 75–84, and 14% were ≥85 years old; 51% were female, and 77% were white. ESS strongly correlated with postoperative mortality (c-statistic:0.81). Mortality gradually increased from 0% to 20%–60% at ESS of 2, 10 and 16 points, respectively. ESS predicted mortality, morbidity, and need for ICU best in patients 65–74 years old (c-statistic:0.81, 0.75, 0.83 respectively), but its performance significantly decreased in patients ≥85 years (c-statistic:0.72, 0.64, 0.67 respectively). ESS is an accurate predictor of outcome in the elderly EL patient 65–85 years old, but its performance decreases for patients ≥85. Consideration should be given to modify ESS to better predict outcomes in the very elderly patient population. •Emergency Surgery Score is a validated preoperative risk calculator in emergency general surgery.•Emergency Surgery Score strongly correlates with postoperative mortality in elderly patients.•Emergency Surgery Score strongly correlates with postoperative morbidity in elderly patients.•The performance of Emergency Surgery Score decreases significantly in patients ≥85 years.

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.sup.[TM] 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<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

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.sup.[TM] 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<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.