Publications by authors named "William Duong"

15 Publications

  • Page 1 of 1

Outcomes after ultramassive transfusion in the modern era: An Eastern Association for the Surgery of Trauma multicenter study.

J Trauma Acute Care Surg 2021 07;91(1):24-33

From the Department of Surgery at Zuckerberg San Francisco General Hospital, University of California San Francisco (Z.A.M., Z.J.H., R.A.C., B.N.-G., L.Z.K., E.E.R., J.J.P., B.R., M.K.A., A.T.F.), San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco (E.C.M), San Francisco, California; Department of Laboratory Medicine, University of California, San Francisco (J.H.E., A.N., J.M.), San Francisco, California; Department of Surgery, University of California Irvine (W.D., J.N.), Irvine, Orange, California; Department of Surgery, Ohio Health Grant Medical Center (A.K.L., M.C.S.), Columbus, Ohio; Department of Surgery, University of Kentucky (S.S.D., J.K.R.), Lexington, Kentucky; Department of Surgery, Miami Valley Hospital (H.L., Y.W., C.H.), Dayton, Ohio; Department of Surgery, R Adams Cowley Shock Trauma Center (A.M.C., R.A.K., P.T.), University of Maryland School of Medicine, Baltimore, Maryland; Department of Surgery, Loma Linda Medical Center (L.P., K.M., X.L.-O.), Loma Linda, California; Department of Surgery, University of Kansas Medical Center (K.T., C.A.G.), Kansas City, Kansas; Department of Surgery, Crozer-Chester Medical Center (S.S.S., A.R.), Upland, Pennsylvania; Department of Surgery, WakeMed Health and Hospitals (A.M., P.U., A.S., B.P., K.T.), Raleigh, North Carolina; Department of Surgery, University of New Mexico School of Medicine (K.M., S.A.M.), Albuquerque, New Mexico; Department of Surgery, Wellspan York Hospital (J.G.), York, Pennsylvania; Department of Surgery, Ascension Via Christi Hospitals St. Francis (J.K., J.H., K.L.), Wichita, Kansas; Department of Surgery, Maine Medical Center (J.B.O., D.C.C.), Portland, Maine; Department of Surgery, South Shore Hospital/Brigham and Women's Hospital (S.A.S., J.C.K.), Boston, Massachusetts; Department of Surgery, Penn State Hershey Medical Center (J.G., J.P.H.), Hershey, Pennsylvania; Department of Surgery, Northwestern University Feinberg School of Medicine (A.Z.B., J.A.P.), Chicago, Illinois; Department of Surgery, University of California (R.A.C.), UC Davis, Sacramento, California; Department of Surgery, Ryder Trauma Center (K.A.J., G.R.), University of Miami Miller School of Medicine, Miami, Florida; and Washington University School of Medicine St. Louis (J.K.), Missouri.

Background: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era.

Methods: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality.

Results: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%).

Conclusion: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication.

Level Of Evidence: Prognostic, level III.
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http://dx.doi.org/10.1097/TA.0000000000003121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243874PMC
July 2021

Analysis of Unintentional Falls in Pediatric Population and Predictors of Morbidity.

J Surg Res 2021 Jun 12;267:48-55. Epub 2021 Jun 12.

Division of Pediatric Surgery, Children's Hospital of Orange County, Orange, California.

Introduction: Unintentional falls are a leading cause of pediatric traumatic injury. This study evaluates clinical outcomes of fall-related injuries in children under the age of 10.

Methods: The National Trauma Database was queried for children who experienced an unintentional fall. Patients were stratified by age in two groups: 1-5 and 6-10 years old. The primary outcome was post discharge extension of care, defined as transfer to skilled nursing facility or rehabilitation center after discharge from the hospital. Descriptive statistics and a multivariable logistic regression analysis were used to compare the two groups.

Results: From 2009 to 2016, a total of 8,277 pediatric patients experienced an unintentional fall, with 93.6% of patients being discharged home. Falls were more common in younger children, with greater odds of post discharge extension of care. Predictors of increased associated risk of extended medical care included intracranial hemorrhage (OR 1.05, 95% CI 1.03-1.06) and thoracic injuries (OR 1.03, 95% CI 1.00-1.1.05) (P< 0.05). Mortality in pediatric patients suffering unintentional falls was a rare event occurring in 0.7% of cases in children 1-5 years old and 0.4% of children 6-10 years old.

Conclusion: The majority of children experiencing an unintentional fall are discharged home, with mortality being very rare. However, younger age is prone to more severe and serious injury patterns. Intracranial hemorrhage and thoracic injury were a predictor of need for extended medical care.
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http://dx.doi.org/10.1016/j.jss.2021.04.036DOI Listing
June 2021

Iatrogenic Arteriovenous Fistula Formation after Endovenous Laser Treatment Resulting in High-output Cardiac Failure: A Case Report and Review of the Literature.

Ann Vasc Surg 2021 Apr 17;72:666.e13-666.e21. Epub 2020 Dec 17.

Division of Vascular and Endovascular Surgery, Department of Surgery, Irvine Medical Center, University of California, Orange, CA. Electronic address:

Formation of a clinically significant iatrogenic arteriovenous fistula after endovenous laser treatment of the great saphenous vein is an extremely rare complication. Because of the infrequency of reported cases, there is no clear consensus on how to best manage this complication. We present a unique case of an iatrogenic high-output superficial femoral artery-common femoral vein fistula resulting in right heart failure and a distal deep vein thrombosis. Deployment of a covered arterial stent graft resulted in resolution of the arteriovenous fistula and high-output cardiac state. Clinically significant arteriovenous fistulas resulting from inadvertent vessel injury during endovenous laser treatment appear to be amenable to percutaneous endovascular interventions. During these challenging endovascular cases, intravascular ultrasonography can be used to help delineate the morphology of the fistula tract and obtain vessel measurements to ensure accurate endoprosthesis sizing and placement.
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http://dx.doi.org/10.1016/j.avsg.2020.10.034DOI Listing
April 2021

Racial and Sex Disparities in Trauma Outcomes Based on Geographical Region.

Am Surg 2021 Jun 9;87(6):988-993. Epub 2020 Dec 9.

Department of Surgery, Division of Trauma and Surgical Critical Care, 8788University of California, Irvine, USA.

Objectives: Disparities in outcomes among trauma patients have been shown to be associated with race and sex. The purpose of this study was to analyze racial and sex mortality disparities in different regions of the United States, hypothesizing that the risk of mortality among black and Asian trauma patients, compared to white trauma patients, will be similar within all regions in the United States.

Methods: The Trauma Quality Improvement Program (2010-2016) was queried for adult trauma patients, separating by U.S. Census regions. Multivariable logistic regression analyses were performed for each region, controlling for known predictors of morbidity and mortality in trauma.

Results: Most trauma patients were treated in the South (n = 522 388, 40.7%). After risk adjustment, black trauma patients had a higher associated risk of death in all regions, except the Northeast, compared to white trauma patients. The highest associated risk of death for blacks (vs. whites) was in the Midwest (odds ratio [OR] 1.30, < .001). Asian trauma patients only had a higher associated risk of death in the West (OR 1.39, < .001). Male trauma patients, compared to women, had an increased associated risk of mortality in all four regions.

Discussion: This study found major differences in outcomes among different races within different regions of the United States. There was also both an increased rate and associated risk of mortality for male patients in all regions. Future prospective studies are needed to identify what regional differences in trauma systems including population density, transport times, hospital access, and other trauma resources explain these findings.
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http://dx.doi.org/10.1177/0003134820960063DOI Listing
June 2021

Evaluation of Pelvic Anastomosis by Endoscopic and Contrast Studies Prior to Ileostomy Closure: Are Both Necessary? A Single Institution Review.

Am Surg 2020 Oct;86(10):1296-1301

Department of Surgery, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, CA, USA.

Contrast enema is the gold standard technique for evaluating a pelvic anastomosis (PA) prior to ileostomy closure. With the increasing use of flexible endoscopic modalities, the need for contrast studies may be unnecessary. The objective of this study is to compare flexible endoscopy and contrast studies for anastomotic inspection prior to defunctioning stoma reversal. Patients with a protected PA undergoing ileostomy closure between July 2014 and June 2019 at our institution were retrospectively identified. Demographics and clinical outcomes in patients undergoing preoperative evaluation with endoscopic and/or contrast studies were analyzed. We identified 207 patients undergoing ileostomy closure. According to surgeon's preference, 91 patients underwent only flexible endoscopy (FE) and 100 patients underwent both endoscopic and contrast evaluation (FE + CE) prior to reversal. There was no significant difference in pelvic anastomotic leak (2.2% vs. 1%), anastomotic stricture (1.1% vs. 6%), pelvic abscess (2.2% vs. 3.0%), or postoperative anastomotic complications (4.4% vs. 9%) between groups FE and FE + CE ( > .05). Flexible endoscopy alone appears to be an acceptable technique for anastomotic evaluation prior to ileostomy closure. Further studies are needed to determine the effectiveness of different diagnostic modalities for pelvic anastomotic inspection.
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http://dx.doi.org/10.1177/0003134820964227DOI Listing
October 2020

University Teaching Trauma Centers: Decreased Mortality but Increased Complications.

J Surg Res 2021 03 24;259:379-386. Epub 2020 Oct 24.

Department of Surgery, University of California, Irvine, Orange, California.

Background: Teaching hospitals are often regarded as excellent institutions with significant resources and prominent academic faculty. However, the involvement of trainees may contribute to higher rates of complications. Conflicting reports exist regarding outcomes between teaching and nonteaching hospitals, and the difference among trauma centers is unknown. We hypothesized that university teaching trauma centers (UTTCs) and nonteaching trauma centers (NTTCs) would have a similar risk of complications and mortality.

Methods: We queried the Trauma Quality Improvement Program (2010-2016) for adults treated at UTTCs or NTTCs. A multivariable logistic regression analysis was performed to evaluate the risk of mortality and in-hospital complications, such as respiratory complications (RCs), venous thromboembolisms (VTEs), and infectious complications (ICs).

Results: From 895,896 patients, 765,802 (85%) were treated at UTTCs and 130,094 (15%) at NTTCs. After adjusting for covariates, UTTCs were associated with an increased risk of RCs (odds ratio (OR) 1.33, confidence interval (CI) 1.28-1.37, P < 0.001), VTEs (OR 1.17, CI 1.12-1.23, P < 0.001), and ICs (OR 1.56, CI 1.49-1.64, P < 0.001). However, UTTCs were associated with decreased mortality (OR 0.96, CI 0.93-0.99, P = 0.008) compared with NTTCs.

Conclusions: Our study demonstrates increased associated risks of RCs, VTEs, and ICs, yet a decreased associated risk of in-hospital mortality for UTTCs when compared with NTTCs. Future studies are needed to identify the underlying causative factors behind these differences.
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http://dx.doi.org/10.1016/j.jss.2020.09.020DOI Listing
March 2021

An increasing trend in geriatric trauma patients undergoing surgical stabilization of rib fractures.

Eur J Trauma Emerg Surg 2020 Oct 23. Epub 2020 Oct 23.

Irvine Medical Center, Department of Surgery, Division of Trauma, Burns and Surgical Critical Care, University of California, 333 The City Blvd West, Suite 1600, Orange, CA, 92868-3298, USA.

Purpose: The proportion of geriatric trauma patients (GTPs) (age ≥ 65 years old) with chest wall injury undergoing surgical stabilization of rib fractures (SSRF) nationally is unknown. We hypothesize a growing trend of GTPs undergoing SSRF, and sought to evaluate risk of respiratory complications and mortality for GTPs compared to younger adults (18-64 years old) undergoing SSRF.

Methods: The Trauma Quality Improvement Program (2010-2016) was queried for patients with rib fracture(s) who underwent SSRF. GTPs were compared to younger adults. A multivariable logistic regression analysis was performed.

Results: From 21,517 patients undergoing SSRF, 3,001 (16.2%) were GTPs. Of all patients undergoing SSRF in 2010, 10.6% occurred on GTPs increasing to 17.9% in 2016 (p < 0.001) with a geometric-mean-annual increase of 11.5%. GTPs had a lower median injury severity score (18 vs. 22, p < 0.001), but had a higher rate of mortality (4.7% vs. 1.2%, p < 0.001). After controlling for covariates, GTPs had an increased associated risk of mortality (OR 4.80, CI 3.62-6.36, p < 0.001). On a separate multivariate analysis for all trauma patients with isolated chest Abbreviated Injury Scale 3, GTPs were associated with a similar four-fold risk of mortality (OR 4.21, CI 1.98-6.32, p < 0.001).

Conclusion: Spanning 7 years of data, the proportion of GTPs undergoing SSRF increased by over 7%. Although GTPs undergoing SSRF had lesser injuries, their risk of mortality was four times higher than other adult trauma patients undergoing SSRF, which was similar to their increased background risk of mortality. Ultimately, SSRF in GTPs should be considered on an individualized basis with careful attention to risk-benefit ratio.
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http://dx.doi.org/10.1007/s00068-020-01526-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583690PMC
October 2020

Comparison of surgical fixation and non-operative management in patients with traumatic sternum fracture.

Eur J Trauma Emerg Surg 2020 Oct 19. Epub 2020 Oct 19.

Department of General Surgery, Division of Trauma, Burns and Surgical Critical Care, University of California, Irvine, 333 City Blvd. West, Suite 1600, Orange, CA, 92868, USA.

Purpose: The incidence of sternal fractures in blunt trauma patients lies between 3 and 7%. The role, timing and indications for surgical management are not well delineated and remain controversial for patients undergoing surgical stabilization of sternum fracture (SSSF). We sought to identify the national rate of SSSF in patients with a sternum fracture hypothesizing patients undergoing SSSF will have a decreased rate of mortality and complications.

Methods: The Trauma Quality Improvement Program (2015-2016) was queried for patients with sternum fracture. Propensity scores were calculated to match patients undergoing SSSF to patients managed non-operatively in a 1:2 ratio using demographic data.

Results: From 9460 patients with a sternum fracture, 114 (1.2%) underwent SSSF. After propensity-matching, 112 SSSF patients were compared to 224 patients undergoing non-operative management (NOM). There were no differences in matched characteristics (all p > 0.05). Compared to patients undergoing NOM, patients undergoing SSSF had an increased median length of stay (LOS) (16 vs. 7 days, p < 0.001), ICU LOS (9.5 vs. 5.5 days, p = 0.016) and ventilator days (8 vs. 5, p = 0.035). The SSSF group had a similar rate of ARDS (2.7% vs. 2.2%, p = 0.80), pneumonia (1.8% vs. 0.9%, p = 0.48) and unplanned intubation (8.9% vs. 5.8%, p = 0.29) but a lower mortality rate (2.7% vs. 11.2%, p = 0.008).

Conclusion: Just over 1% of patients with sternum fracture underwent SSSF in a national analysis. Patients undergoing SSSF had an increased LOS and similar rate of all measured pulmonary complications, however a lower mortality rate compared to patients managed non-operatively.
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http://dx.doi.org/10.1007/s00068-020-01527-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571865PMC
October 2020

Research priorities in chest wall injury: A modified Delphi approach.

J Trauma Acute Care Surg 2020 10;89(4):e106-e111

From the Division of Trauma, Burns and Surgical Critical Care, Department of Surgery (A.B.C., P.T.D., A.G., J.N., E.T., W.Q.D., W.Y.R., S.D.S.), University of California, Irvine, Orange, California, and Department of Surgery (L.M.), University of North Dakota, Grand Forks, North Dakota.

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http://dx.doi.org/10.1097/TA.0000000000002854DOI Listing
October 2020

Evolving Utility of Endovascular Treatment of Juxtarenal, Pararenal, and Suprarenal Abdominal Aortic Aneurysms Associated With Increased Risk of Mortality Over Time.

Ann Vasc Surg 2021 Feb 2;71:428-436. Epub 2020 Sep 2.

University of California, Irvine, Department of Surgery, Orange, CA.

Background: Continued advances in endovascular technologies are resulting in fewer open abdominal aortic aneurysm (AAA) repairs. In addition, more complex juxtarenal, pararenal, and suprarenal (JPS) AAAs are being managed with various endovascular techniques. This study sought to evaluate the evolving trends in endovascular aneurysm repair (EVAR) of AAAs, hypothesizing increased rate of JPS AAA repair by EVAR. We also sought to evaluate the risk for morbidity and mortality for EVAR and open aneurysm repair (OAR) of JPS AAAs over time.

Methods: The 2011-2017 American College of Surgeons National Surgical Quality Improvement Program Procedure-Targeted Vascular database was queried for patients undergoing OAR or EVAR for AAAs. A multivariable logistic regression analysis was performed for both infrarenal and JPS AAA repairs.

Results: Of 18,661 patients who underwent AAA repair, 3,941 (21.1%) were OAR and 14,720 (78.9%) were EVAR. The rate of OAR decreased from 29.5% in 2011 to 21.3% in 2017 (P < 0.001) with a geometric-mean-annual decrease of 27.8%. The rate of EVAR increased from 70.5% to 78.7% during the same time period (P < 0.001) with a geometric-mean-annual increase of 11.6%. These trends remained true for both infrarenal and JPS AAAs. After adjusting for covariates, there was no difference in associated risk of 30-day mortality, renal complications, or ischemic colitis for either OAR or EVAR over each incremental year for infrarenal AAAs (P > 0.05). However, in patients undergoing EVAR for JPS AAAs, the associated risk of mortality increased with each incremental year (odds ratio [OR]: 1.30, confidence interval [CI]: 1.01-1.69, P = 0.039), whereas there was no difference in the risk of mortality for OAR of JPS AAAs with each incremental year (OR: 1.11, CI: 0.99-1.23, P = 0.067).

Conclusions: The rate of OAR for AAA has decreased over the past seven years with an increase in EVAR, particularly for more complex JPS AAAs. The associated risk for morbidity and mortality for treatment of infrarenal AAAs was not significantly affected by this increased utility of EVAR. The associated risk of mortality for JPS AAAs treated by EVAR increased over time, whereas this trend for associated risk of mortality was not seen for OAR of JPS AAAs. These findings, especially the increased associated risk of mortality over time with EVAR for JPS AAAs, warrant careful prospective analysis.
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http://dx.doi.org/10.1016/j.avsg.2020.08.103DOI Listing
February 2021

Analysis of Endovascular Aneurysm Repair for Small Abdominal Aortic Aneurysms in Males.

J Surg Res 2020 12 21;256:163-170. Epub 2020 Jul 21.

Division of Trauma, Burns, and Surgical Critical Care, Department of Surgery, University of California, Irvine, Orange, California. Electronic address:

Background: Current guidelines recommend repair of abdominal aortic aneurysms (AAAs) when ≥5.5 cm. This study sought to evaluate the incidence of male patients undergoing endovascular aneurysm repair (EVAR) for AAAs of various diameters (small <4 cm; intermediate 4-5.4 cm; standard ≥5.5 cm). We analyzed predictors of mortality, hypothesizing that smaller AAAs (<5.5 cm) have no differences in associated risk of mortality compared to standard AAAs (≥5.5 cm).

Methods: The 2011-2017 American College of Surgeons National Surgical Quality Improvement Program Procedure-Targeted Vascular database was queried for male patients undergoing elective EVAR. Patients were stratified by aneurysm diameter. A multivariable logistic regression analysis for clinical outcomes, adjusting for age, clinical characteristics, and comorbidities, was performed.

Results: A total of 8037 male patients underwent EVAR with 3926 (48.9%) performed for AAAs <5.5 cm. There was no difference in mortality, readmission, major complications, myocardial infarction, stroke, or ischemic complications among the 3 groups (P > 0.05). In AAAs <5.5 cm, predictors of mortality included prior abdominal surgery (odds ratio [OR], 5.77; confidence interval [CI], 1.38-24.13; P = 0.016), weight loss (OR, 43.4; CI, 3.78-498.7; P = 0.002), disseminated cancer (OR, 17.9; CI, 1.30-245.97; P = 0.031), and diabetes (OR, 6.09; CI, 1.52-24.36; P = 0.011).

Conclusions: Nearly 50% of male patients undergoing elective EVAR were treated for AAAs <5.5 cm. There was no difference in associated risk of mortality for smaller AAAs compared to standard AAAs. The strongest predictors of mortality for patients with smaller AAAs were prior abdominal surgery, weight loss, disseminated cancer, and diabetes.
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http://dx.doi.org/10.1016/j.jss.2020.06.030DOI Listing
December 2020

Implementation of a High-Value Care Curriculum for General Surgery Residents.

J Surg Educ 2020 Sep - Oct;77(5):1194-1201. Epub 2020 Mar 31.

Department of Surgery, University of California, Irvine, Orange, California.

Introduction: Healthcare expenditures account for more than 3.5 trillion dollars annually with estimates of nearly one-half being wasteful. High-value care (HVC) balances the benefits, harms, and costs of healthcare. Since 2012, the American College of Physicians and Accreditation Council for Graduate Medical Education developed a HVC curriculum and incorporated HVC into milestones for medicine residents. However, currently no HVC curriculum or milestones exist for general surgery residents (GSR). We sought to implement a HVC curriculum for GSR and evaluate awareness and attitudes toward HVC, hypothesizing improved resident awareness and attitudes toward HVC without affecting patient outcomes.

Methods: A prospective comparison between pre-HVC curriculum (7/1/2017-11/30/2017) and post-HVC curriculum (2/1/2018-6/30/2018) was performed. The curriculum included 6 didactic lectures with group discussions. A 14-question Likert-scale survey evaluating awareness, use of, and attitudes toward HVC was performed on all GSR. Additional patient outcomes were collected for all trauma patients cared for during the study period. Bivariate analysis using Mann-Whitney U test was performed.

Results: There were 38/38 GSR respondents (100% response rate) for the pre-HVC survey and 35/38 (92.1% response rate) for the post-HVC survey. More post-HVC respondents somewhat agreed (34.3% vs 5.3%) and less strongly disagreed (31.4% vs 52.6%) with improved knowledge of where to find costs of labs/imaging/treatment (p = 0.02) compared to the pre-HVC group. More post-HVC respondents strongly agreed they balanced the benefit of clinical care with costs and harm when treating patients (25.7% vs 21.1%; p = 0.01). More post-HVC respondents strongly agreed they customized care plans to incorporate patients' values/concerns after implementation of the curriculum (51.4% vs 23.7%, p = 0.0006). From 3254 trauma patients studied, 1722 (52.9%) were pre-HVC and 1532 (47.1%) post-HVC patients. There was no difference between the pre- and post-HVC-curriculum trauma patients in terms of demographics and outcomes such as mortality (3.6% vs 2.4%, p = 0.07) and median length of stay (2 vs 2 days, p = 0.6).

Conclusions: Implementation of a HVC curriculum for GSR led to improved awareness regarding healthcare costs and customizing decision plans for patients, with no difference in trauma patient outcomes. Future research incorporating cost data is needed; however, with implementation of the 2020 general surgery milestones (addition of Systems-Based Practice-3), this curriculum could prove beneficial.
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http://dx.doi.org/10.1016/j.jsurg.2020.03.006DOI Listing
June 2021

Sternotomy for Hemorrhage Control in Trauma.

J Surg Res 2020 03 20;247:227-233. Epub 2019 Nov 20.

Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, University of California, Irvine, California.

Background: Little is known about the injuries, mechanisms, and outcomes in trauma patients undergoing sternotomy for hemorrhage control (SHC). The purpose of this study was to identify predictors of mortality for SHC and provide a descriptive analysis of the use of SHC in trauma. We hypothesize blunt trauma is associated with higher mortality compared with penetrating trauma among trauma patients requiring SHC.

Methods: The Trauma Quality Improvement Program (2013-2016) database was queried for adult patients undergoing SHC within 24 h of admission. Patients with blunt and penetrating trauma were compared using chi-square and Mann-Whitney U-test. A multivariable logistic regression model was used to determine the risk of mortality.

Results: Of 584 patients undergoing SHC, 322 (55.1%) were involved in penetrating trauma, and 69 (11.8%) were involved in blunt. The blunt trauma group had a higher median injury severity score (31.5 versus 25.0; P < 0.001) compared with the penetrating group. The median time to hemorrhage control was longer in those with blunt compared with penetrating trauma (84.6 versus 49.8 min; P < 0.001). The mortality rate was higher in patients with blunt compared with penetrating trauma (29.0% versus 12.7%; P < 0.001). However, after adjusting for covariates, there was no difference in risk of mortality between blunt and penetrating trauma (P = 0.06).

Conclusions: Trauma patients requiring SHC after blunt trauma had a higher mortality rate than those in penetrating trauma. After adjusting for predictors of mortality, there was no difference in risk of mortality despite nearly double the time to hemorrhage control in patients presenting after blunt trauma.
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http://dx.doi.org/10.1016/j.jss.2019.09.071DOI Listing
March 2020

Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening.

Cell 2017 Jul;170(3):577-592.e10

Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.
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http://dx.doi.org/10.1016/j.cell.2017.07.005DOI Listing
July 2017

Oestrogen receptor β regulates epigenetic patterns at specific genomic loci through interaction with thymine DNA glycosylase.

Epigenetics Chromatin 2016 16;9. Epub 2016 Feb 16.

Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.

Background: DNA methylation is one way to encode epigenetic information and plays a crucial role in regulating gene expression during embryonic development. DNA methylation marks are established by the DNA methyltransferases and, recently, a mechanism for active DNA demethylation has emerged involving the ten-eleven translocator proteins and thymine DNA glycosylase (TDG). However, so far it is not clear how these enzymes are recruited to, and regulate DNA methylation at, specific genomic loci. A number of studies imply that sequence-specific transcription factors are involved in targeting DNA methylation and demethylation processes. Oestrogen receptor beta (ERβ) is a ligand-inducible transcription factor regulating gene expression in response to the female sex hormone oestrogen. Previously, we found that ERβ deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERβ in DNA methylation. In this study, we set out to explore this involvement on a genome-wide level, and to investigate the underlying mechanisms of this function.

Results: Using reduced representation bisulfite sequencing, we compared genome-wide DNA methylation in mouse embryonic fibroblasts derived from wildtype and ERβ knock-out mice, and identified around 8000 differentially methylated positions (DMPs). Validation and further characterisation of selected DMPs showed that differences in methylation correlated with changes in expression of the nearest gene. Additionally, re-introduction of ERβ into the knock-out cells could reverse hypermethylation and reactivate expression of some of the genes. We also show that ERβ is recruited to regions around hypermethylated DMPs. Finally, we demonstrate here that ERβ interacts with TDG and that TDG binds ERβ-dependently to hypermethylated DMPs.

Conclusion: We provide evidence that ERβ plays a role in regulating DNA methylation at specific genomic loci, likely as the result of its interaction with TDG at these regions. Our findings imply a novel function of ERβ, beyond direct transcriptional control, in regulating DNA methylation at target genes. Further, they shed light on the question how DNA methylation is regulated at specific genomic loci by supporting a concept in which sequence-specific transcription factors can target factors that regulate DNA methylation patterns.
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http://dx.doi.org/10.1186/s13072-016-0055-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756533PMC
February 2016
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