Deterioration Index in Critically Injured Patients: A Feasibility Analysis.

INTRODUCTION: Continuous prediction surveillance modeling is an emerging tool giving dynamic insight into conditions with potential mitigation of adverse events (AEs) and failure to rescue. The Epic electronic medical record contains a Deterioration Index (DI) algorithm that generates a prediction score every 15 min using objective data. Previous validation studies show rapid increases in DI score (≥14) predict a worse prognosis. The aim of this study was to demonstrate the utility of DI scores in the trauma intensive care unit (ICU) population. METHODS: A prospective, single-center study of trauma ICU patients in a Level 1 trauma center was conducted during a 3-mo period. Charts were reviewed every 24 h for minimum and maximum DI score, largest score change (Δ), and AE. Patients were grouped as low risk (ΔDI <14) or high risk (ΔDI ≥14). RESULTS: A total of 224 patients were evaluated. High-risk patients were more likely to experience AEs (69.0% versus 47.6%, P = 0.002). No patients with DI scores <30 were readmitted to the ICU after being stepped down to the floor. Patients that were readmitted and subsequently died all had DI scores of ≥60 when first stepped down from the ICU. CONCLUSIONS: This study demonstrates DI scores predict decompensation risk in the surgical ICU population, which may otherwise go unnoticed in real time. This can identify patients at risk of AE when transferred to the floor. Using the DI model could alert providers to increase surveillance in high-risk patients to mitigate unplanned returns to the ICU and failure to rescue.

Venovenous Extracorporeal Membrane Oxygenation Usage Following Bullet Embolism to the Pulmonary Artery.

Background: Pulmonary artery embolus is a rare complication following gunshot wounds that creates a unique and serious challenge for trauma surgeons. While the majority of bullets that embolize through the vascular system end in the peripheral circulation, approximately one-third enter the central venous circulation. Case Report: We present the case of a bullet embolus to the left pulmonary artery following gunshot wounds to the right chest and the abdomen, with the abdominal ballistic traversing the liver before entering the vena cava and embolizing. The patient's course was complicated by the development of severe acute respiratory distress syndrome that was successfully managed by venovenous extracorporeal membrane oxygenation. Conclusion: Venovenous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome after bullet embolization to the pulmonary tree and surgical embolectomy is a viable option in appropriately selected patients.

The Impact of Pre-Trauma Steroid Use on Wound Healing and Outcomes.

This study presents data on pre-trauma steroid use, a topic underrepresented in the trauma literature. Long-term steroid use has been linked to impaired wound healing, compromised immune responses, and hindrance of bone healing, alongside the potential for adrenal insufficiency during traumatic events. The aim of this study was to conduct a retrospective analysis of clinical outcomes for trauma patients with chronic steroid use. Examining adult trauma cases with pre-trauma steroid use at a level 1 trauma center (January 2016-September 2023), we identified 18 patients (58.6 ± 19.4 years, 55.6% males). All were on prednisone prior to trauma activation and 66.7% had autoimmune disease. Complications included orthopedic fractures (72.2%), ICU admissions (16.7%), and low mortality (5.6%). Future larger, multi-center studies are needed to determine the impact of immunosuppression and pre-trauma steroids on clinical outcomes.

Risk Factors for Empyema Following Penetrating Diaphragmatic Injuries.

Empyema resulting as a complication of penetrating diaphragmatic injuries is a subject that requires further investigation, and the aim of this study was to determine the risk factors associated with empyema in patients with penetrating trauma. Consecutive adult trauma patients from a level 1 trauma center were searched for penetrating diaphragm injuries. Data were collected on patient demographics, pre-existing conditions, injury type and severity, hospital interventions, in-hospital complications, and outcomes. Patients were stratified by empyema formation and univariant analyses were performed. 164 patients were identified, and 17 patients (10.4%) developed empyema. Empyema was associated with visible abdominal contamination (35.3% vs 15%, P = .04), thoracotomy (35.5% vs 13.6%, P = .03), pneumonia (41.2% vs 14.3%, P = .01), sepsis (35.3% vs 8.8%, P = .006), increased hospital length of stay (25.5 vs 10.1 days, p =<.001), increased intensive care unit length of stay (9.6 vs 4.3 days, P = .01), and decreased in-hospital mortality (0% vs 20.4%, P = .04).

Traumatic Abdominal Wall Hernia: Management Using a Standardized Approach.

Traumatic abdominal wall hernias are a rare complication of high energy blunt trauma. There exist several studies evaluating and outlining potential management options but still no generalized consensus on management. This series was meant to evaluate the diagnosis and management of traumatic abdominal wall hernias. A prospectively maintained database was used to identify patients with TAWH from 2021 to 2022. The primary outcome was operative management. Secondary outcomes included: time to diagnosis and post-operative outcomes. Of the 19 patients in this case series, 100% (n = 19/19) were secondary to blunt trauma with a mean ISS of 21. Exploratory laparotomy was performed in 17 cases. 14 cases had concomitant traumatic injuries to visceral structures. Complications were found in nearly half of the patients with 3 experiencing wound dehiscence. Future studies should be aimed at standardizing management approach taking into account nature of the mechanism and concomitant injuries.

Discrepancies in Mass Shootings and Access to Trauma Care Across the United States, 2014-2018.

INTRODUCTION: The United States has one of the highest rates of gun violence and mass shootings. Timely medical attention in such events is critical. The objective of this study was to assess geographic disparities in mass shootings and access to trauma centers. METHODS: Data for all Level I and II trauma centers were extracted from the American College of Surgeons and the Trauma Center Association of America registries. Mass shooting event data (4+ individuals shot at a single event) were taken from the Gun Violence Archive between 2014 and 2018. RESULTS: A total of 564 trauma centers and 1672 mass shootings were included. Ratios of the number of mass shootings vs trauma centers per state ranged from 0 to 11.0 mass shootings per trauma center. States with the greatest disparity (highest ratio) included Louisiana and New Mexico. CONCLUSION: States in the southern regions of the US experience the greatest disparity due to a high burden of mass shootings with less access to trauma centers. Interventions are needed to increase access to trauma care and reduce mass shootings in these medically underserved areas.

Chest Tube Size Selection: Evaluating Provider Practices, Treatment Efficacy, and Complications in Management of Thoracic Trauma.

BACKGROUND: The standard for managing traumatic pneumothorax (PTX), hemothorax (HTX), and hemopneumothorax (HPTX) has historically been large-bore (LB) chest tubes (>20-Fr). Previous studies have shown equal efficacy of small-bore (SB) chest tubes (≤19-Fr) in draining PTX and HTX/HPTX. This study aimed to evaluate provider practice patterns, treatment efficacy, and complications related to the selection of chest tube sizes for patients with thoracic trauma. METHODS: A retrospective chart review was performed on adult patients who underwent tube thoracostomy for traumatic PTX, HTX, or HPTX at a Level 1 Trauma Center from January 2016 to December 2021. Comparison was made between SB and LB thoracostomy tubes. The primary outcome was indication for chest tube placement based on injury pattern. Secondary outcomes included retained hemothorax, insertion-related complications, and duration of chest tube placement. Univariate and multivariate analyses were performed. RESULTS: Three hundred and forty-one patients were included and 297 (87.1%) received LB tubes. No significant differences were found between the groups concerning tube failure and insertion-related complications. LB tubes were more frequently placed in patients with penetrating MOI, higher average ISS, and higher average thoracic AIS. Patients who received LB chest tubes experienced a higher incidence of retained HTX. DISCUSSION: In patients with thoracic trauma, both SB and LB chest tubes may be used for treatment. SB tubes are typically placed in nonemergent situations, and there is apparent provider bias for LB tubes. A future randomized clinical trial is needed to provide additional data on the usage of SB tubes in emergent situations.

Acute Kidney Injury in Hypotensive Trauma Patients Following Resuscitative Endovascular Balloon Occlusion of the Aorta Placement.

BACKGROUND: ER-Resuscitative Endovascular Balloon Occlusion of the Aorta (ER-REBOA) is an adjunct tool to achieve hemostasis in trauma patients with non-compressible torso hemorrhage. The development of the partial REBOA (pREBOA) allows for distal perfusion of organs while maintaining occlusion of the aorta. The primary aim of this study was to compare rates of acute kidney injury (AKI) in trauma patients who had placement of either a pREBOA or ER-REBOA. METHODS: A retrospective chart review of adult trauma patients who underwent REBOA placement between September 2017 and February 2022 was performed. Baseline demographics, information on REBOA placement, and post-procedure complications including AKI, amputations, and mortality were recorded. Chi-squared and T-test analyses were performed with P < .05 considered to be significant. RESULTS: A total of 68 patients met study inclusion criteria with 53 patients (77.9%) having an ER-REBOA. 6.7% of patients treated with pREBOA had a resulting AKI, while 40% of patients treated with ER-REBOA had a resulting AKI, and this difference was significant (P < .05). The rates of rhabdomyolysis, amputations, and mortality were not significantly different between the two groups. CONCLUSION: The results from this case series suggest that patients treated with pREBOA have a significantly lower incidence of developing an AKI compared to ER-REBOA. There were no significant differences in rates of mortality, and amputations. Future prospective studies are needed to further characterize the indications and optimal use for pREBOA.

Perioperative Fluid Management in Surgical Patients: A Review.

Intravenous (IV) fluids are one of the most widely prescribed medications. Despite their frequent usage, IV fluids are often not used appropriately. High-quality evidence to guide the surgeon in the perioperative period is sparse. A plethora of choices for IV fluids exists with limited evidence to help guide the surgeon in specific patient populations and situations. To address this, the authors have set out to provide a critical review of commonly used IV fluids to treat surgical patients. Gaps in the existing literature for the surgical population will also be discussed as potential target areas for future research.

Does Vehicle Intrusion Alone Still Predict Injury: A Retrospective Analysis of Mechanism as Trauma Activation Criteria.

Automobile collisions with driver side intrusion >12 inches or >18 elsewhere meet criteria for trauma activation. However, vehicle safety features have improved since this inception. We hypothesized vehicle intrusion (VI) alone as mechanism-of-injury (MOI) criteria inadequately predicts trauma center activation. A retrospective, single-center chart review of adult patients involved in motor vehicle collisions presenting to a level 1 trauma center from July 2016 to March 2022 was performed. Patients were divided by MOI criteria: VI vs. multiple MOI criteria. 2940 patients met inclusion criteria. The VI group reported lower injury severity scores (P = 0.004), higher incidence of ED discharge (P = 0.001), lower ICU admissions (P = 0.004), and fewer in-hospital procedures (P = 0.03). Vehicle intrusion was found to have a positive likelihood ratio of 0.889 for predicting trauma center need. According to current guidelines, these results suggest that VI criteria alone may not be an accurate predictor for trauma center transport and require further investigation.

Comparison of rampage and non-rampage mass shootings in the U.S.: A 5-year demographic analysis.

BACKGROUND: Rampage mass shootings (RMS) are a subset of mass shootings occurring in public involving random victims. Due to rarity, RMS are not well-characterized. We aimed to compare RMS and NRMS. We hypothesized that RMS and NRMS would be significantly different with respect to time/season, location, demographics, victim number/fatality rate, victims being law enforcement, and firearm characteristics. STUDY DESIGN: Mass shootings (4 or more victims shot at a single event) from 2014-2018 were identified in the Gun Violence Archive (GVA). Data were collected from the public domain (e.g. news). Crude comparisons between NRMS and RMS were performed using Chi-squared or Fisher's exact tests. Parametric models of victim and perpetrator characteristics were conducted at the event level using negative binomial regression and logistic regression. RESULTS: There were 46 RMS and 1626 NRMS. RMS occurred most in businesses (43.5%), whereas NRMS occurred most in streets (41.1%), homes (28.6%), and bars (17.9%). RMS were more likely to occur between 6AM-6PM (OR=9.0 (4.8-16.8)). RMS had more victims per incident (23.6 vs. 4.9, RR: 4.8 (4.3,5.4)). Casualties of RMS were more likely to die (29.7% vs. 19.9%, OR: 1.7 (1.5,2.0)). RMS were more likely to have at least one police casualty (30.4% versus 1.8%, OR: 24.1 (11.6,49.9)) or police death (10.9% versus 0.6%, OR: 19.7 (6.4,60.3)). RMS had significantly greater odds that casualties were adult (OR: 1.3 (1.0,1.6)) and female (OR: 1.7 (1.4,2.1)). Deaths in RMS were more likely to be female (OR: 2.0 (1.5,2.5)) and White (OR: 8.6 (6.2,12.0) and less likely to be children (OR: 0.4 (0.2,0.8)). Perpetrators of RMS were more likely to die by suicide (34.8%), be killed by police (28.3%), or be arrested at the scene (26.1%), while more than half of perpetrators from NRMS escaped without death or apprehension (55.8%). Parametric models of perpetrator demographics indicated significant increases in the odds that a RMS shooter was White (OR: 13.9 (7.3,26.6)) or Asian (OR: 16.9 (3.7,78.4)). There was no significant difference in weapon type used (p=0.35). CONCLUSION: The demographics, temporality, and location differ between RMS and NRMS, suggesting that they are dissimilar and require different preventive approaches.

The COVID-19 pandemic and its impacts on mass shootings in six major US cities.

BACKGROUND: The COVID-19 pandemic has significant impacts on the US socioeconomic structure. Gun violence is a major public health issue and the effects on this area have not been well-elucidated. The objective of this study was to determine the impacts of the pandemic on mass shootings in six major United States cities with historically high rates of gun violence. METHODS: Mass shooting data were extracted from an open-source database, Gun Violence Archive. Mass shooting was defined as four or more people shot at a single event. Data from six cities with the highest incidence of mass shootings were analyzed in 2019 versus 2020 (Baltimore, Chicago, Detroit, New Orleans, Philadelphia, and St. Louis). Geographic data were examined to assess changes in each city's mass shooting geographic distribution over time. Quantitative changes were assessed using the Area Deprivation Index (ADI), and qualitative data were assessed using ArcGIS. RESULTS: In 2020, the overall percentage of mass shootings increased by 46.7% though there was no change in the distribution of these events when assessed quantitatively (no change in average ADI) nor qualitatively (using ArcGIS). In the six cities analyzed, the total proportion of mass shooting events was unchanged during the pandemic (21.8% vs 20.6%, p = 0.64). Chicago, the US city with the highest incidence of mass shootings, did not experience a significant change in 2020 (n = 34/91, 37.3% vs. n = 53/126, 42.1%, p = 0.57). Baltimore had a significant decrease in mass shooting events (n = 18/91, 19.8% vs. 10/126, 7.9%, p = 0.01). The other four cities had no significant change in the number of mass shootings (p>0.05). CONCLUSION: This study is the first to use ArcGIS technology to describe the patterns of mass shooting in six major US cities during the COVID-19 pandemic. The number of mass shootings in six US cities remained largely unchanged which suggests that changes in mass shootings is likely occurring in smaller cities. Future studies should focus on the changing patterns of homicides in at-risk communities and other possible social influences.

How Did the COVID-19 Pandemic Affect Trauma Volume at an Urban Level I Trauma Center?

INTRODUCTION: The COVID-19 pandemic changed the face of health care worldwide. While the impacts from this catastrophe are still being measured, it is important to understand how this pandemic impacted existing health care systems. As such, the objective of this study was to quantify its effects on trauma volume at an urban Level 1 trauma center in one of the earliest and most significantly affected US cities. METHODS: A retrospective chart review of consecutive trauma patients admitted to a Level 1 trauma center from January 1, 2017 to December 31, 2020 was completed. The total trauma volume in the years prior to the pandemic (2017-2019) was compared to the volume in 2020. These data were then further stratified to compare quarterly volume across all 4 years. RESULTS: A total of 4138 trauma patients were treated in the emergency room throughout 2020 with 4124 seen during 2019, 3774 during 2018, and 3505 during 2017 in the pre-COVID-19 time period. No significant difference in the volume of minor trauma or trauma transfers was observed (P < .05). However, there was a significant increase in the number of major traumas in 2020 as compared to prior years (38.5% vs 35.6%, P < .01) and in the volume of penetrating trauma (29.1% vs 24.0%, P < .01). DISCUSSION: During the COVID-19 outbreak, trauma remained a significant health care concern. This study found an increase in volume of penetrating trauma, specifically gunshot wounds throughout 2020. It remains important to continue to devote resources to trauma patients during the ongoing COVID-19 pandemic.

Prehospital Tourniquets Placed on Limbs Without Major Vascular Injuries, Has the Pendulum Swung Too Far?

BACKGROUND: Combat applications of tourniquets for extremity trauma have led to increased civilian prehospital tourniquet use. Studies have demonstrated that appropriate prehospital tourniquet application can decrease the incidence of arrival in shock without increasing limb complications. The aim of this study was to examine outcomes of prehospital tourniquet placement without definitive vascular injury. METHODS: Retrospective review was performed of a prospectively maintained database by the American Association for the Surgery of Trauma from 29 trauma centers. Patients in this subset analysis did not have a significant vascular injury as determined by imaging or intra-operatively. Patients who received prehospital tourniquets (PHTQ) were compared to patients without prehospital tourniquets (No-PHTQ). Outcomes were amputation rates, nerve palsy, compartment syndrome, and in-hospital mortality. RESULTS: A total of 622 patients had no major vascular injury. The incidence of patients without major vascular injury was higher in the PHTQ group (n = 585/962, 60.8 vs n = 37/88, 42.0%, P < .001). Cohorts were similar in age, gender, penetrating mechanism, injury severity scores (ISS), abbreviated injury score (AIS), and mortality (P > .05). Amputation rates were 8.3% (n = 49/585) in the PHTQ group compared to 0% (n = 0/37) in the No-PHTQ group. Amputation rates were higher in PHTQ than No-PHTQ with similar ISS and AIS (P = .96, P = .59). The incidence of nerve palsy and compartment syndrome was not different (P > .05). CONCLUSIONS: This study showed a significant amount of prehospital tourniquets are being placed on patients without vascular injuries. Further studies are needed to elucidate the appropriateness of prehospital tourniquets, including targeted education of tourniquet placement.

A Retrospective Review of the Timing of Glasgow Coma Scale Documentation in a Trauma Database: Implications for Patient Care, Research, and Performance Metrics.

BACKGROUND: The Glasgow Coma Scale (GCS) is intended to be an objective, reliable measure of a patient's mental status. It is included as a metric for trauma registries, having implications for performance metrics and research. Our study compared the GCS recorded in the trauma registry (GCS-1) with that recorded in the neurosurgery consultation (GCS-2). METHODS: This retrospective review compared GCS-1 with GCS-2. The Trauma Injury Severity Score (TRISS) method was used to calculate probability of survival (POS) for patients using both GCS-1 and GCS-2. RESULTS: GCS-1 score significantly differed from GCS-2 score (6.69 vs. 7.84, ± 2.553; P < 0.001). There were 172 patients (37.55%) with a GCS-1 score of 3 and 87 (19.00%) with a GCS-2 score of 3 (χ2P < 0.001). The POS calculated using TRISS methodology with GCS-1 (POS-1) was 74.7% ± 26.6% compared with GCS-2 (POS-2), which was 79.3% ± 24.4%. There was a statistically significant difference in the means of POS-2 and POS-2 (P < 0.001). The actual observed survival for the cohort was 71.0% (325/458). CONCLUSIONS: The immediate GCS score recorded on patient arrival after trauma differs significantly from the GCS score recorded at later times. This finding significantly altered the probability of survival as calculated by the TRISS methodology. This situation could have profound effects on risk-adjusted benchmarking, assessments of quality of care, and injury severity stratification for research. More studies into the optimal timing of GCS score recording or changes in GCS score and their impact on survival are warranted.

Does Time to Pelvic Fixation Influence Outcomes in Trauma Patients?

BACKGROUND: Pelvic fractures cause significant morbidity in the trauma population. Many factors influence time to fracture fixation. No previous study has determined the optimal time window for pelvic fixation. METHODS: A retrospective review of trauma patients with pelvic fractures from 2016 to 2020 was performed. Patients were stratified into EARLY and LATE groups, by time to fixation within 3 days or greater than 3 days whether from admission or from completion of a life-saving procedure. Unpaired Student's t-test and Fisher's exact test were performed with multiple linear regression for variables with P < .2 on univariate analysis. RESULTS: 287 patients were identified with a median fixation time of 3 days. There was no significant difference in demographics, incidence of preceding life-saving procedure, angioembolization, or mechanism of injury in the 2 groups (P > .05). Length of stay in the EARLY group was significantly reduced at 11.9 +/- .7 days compared to 18.0 +/-1.2 days in the LATE group (P < .001). There was no significant difference in rates of ventilator-associated pneumonia, deep vein thrombosis, pulmonary embolism (PE), acute kidney injury (AKI), pressure ulcer, or acute respiratory distress syndrome (ARDS) (P > .05). There were significantly more SSIs (surgical site infections) in the LATE group. After multiple linear regression adjusting for covariates of age and ISS, the difference in hospital LOS was 5.5 days (95% CI -8.0 to -3.1, P < .001). DISCUSSION: Fixation of traumatic pelvic fractures within 3 days reduced LOS. Prospective multi-center studies will help identify additional factors to decrease time to surgery and improve patient outcomes.

Impact of Increased Enoxaparin Dosing on Anti-Xa Levels for Venous Thromboembolism Prophylaxis in Trauma Patients.

INTRODUCTION: Venous thromboembolism (VTE) contributes to significant morbidity in trauma patients while increasing hospital costs and length of stay. Standard trauma prophylaxis dosing with enoxaparin 30 mg twice daily may be inadequate to prevent VTEs. The objective of this study was to compare standard dosing of enoxaparin to an increased dose of enoxaparin 40 mg twice daily for trauma patients. We hypothesized that increasing thromboprophylaxis dosing leads to an increase in therapeutic anti-Xa levels and reduced VTE rates. METHODS: A retrospective study was performed from January 2020 to June 2021 at a Level I trauma center, following implementation of an increased enoxaparin dosing strategy. Patients with increased enoxaparin dosing were compared with those who received standard dosing. The primary outcome evaluated was the incidence of subtherapeutic anti-Xa levels. Secondary outcomes evaluated VTE rates and clinically significant bleed. RESULTS: A total of 204 trauma patients were identified. Ninety-one patients received an increased enoxaparin dose compared to 113 who received standard dosing. The baseline demographics of both groups were similar (P > .05). Subtherapeutic levels were higher with standard dosing compared to the increased dose (50 vs 22%, P = .003). Higher VTE rates were observed with standard dosing compared to higher dosing (6.2 vs 3.3%) but with a lower incidence of major bleed (1.8 vs 4.4%). Overall annual VTE rates decreased from 1.6 to 1.3% after implementation of the increased dosing regimen. CONCLUSIONS: This study demonstrated that an increased dosing strategy decreased rates of subtherapeutic anti-Xa levels and trended toward lower overall VTE rates in trauma.

Proposed Treatment Algorithm for Invasive Fungal Infections in Trauma Patients.

Background: Invasive fungal infections, most commonly caused by Mucorales species, are an underrecognized sequalae of traumatic injury that can complicate management of patients. The injury mechanism can introduce environmental spores into areas of the body normally not exposed to pathogens and this inoculation can progress rapidly to severe disease. The objective of this study was to present a case series of four trauma patients with invasive fungal infections that was used to develop an algorithm for work-up and treatment of these complex patients in future admissions. Patients and Methods: Four trauma patients who developed mucormycosis from two different hospitals are presented. One patient succumbed to their injuries whereas three were able to clear their infection with medical and surgical intervention. The surviving patients all had an infection of their lower extremity whereas the deceased patient had more extensive disease involving the thorax. Conclusions: Mucormycosis is a rare but significant post-trauma complication with substantial morbidity and mortality. Surgeons should be aware of this complication and maintain a high clinical suspicion because afflicted patients may not match the traditional clinical picture of a mucormycosis-susceptible patient. Close coordination with a pathology service is required for confirmation of the diagnosis and timely intervention can prevent debilitating loss of tissue or death. Additionally, consideration should be given to newer treatment modalities for management such as local tissue irrigation with an antifungal agent.

Compression of the Right Atrium and Inferior Vena Cava from an Extrahepatic Biloma Following Liver Trauma.

A 26-year-old male presented to a Level 1 trauma center following a motorcycle crash. Workup of his injuries demonstrated a grade 5 liver laceration with active extravasation, grade 5 kidney laceration, right apical pneumothorax, and a sternal fracture. The patient underwent hepatic artery embolization with interventional radiology (IR) followed by an exploratory laparotomy, liver packing, and small bowel resection with primary anastomosis. Four days post-op, the patient developed dyspnea, tachycardia, and decreasing oxygen saturation. Computed tomography pulmonary angiography demonstrated perihepatic fluid compressing the right atrium and inferior vena cava. Percutaneous perihepatic drain placement with aspiration of 700 mL bilious fluid resulted in immediate resolution of the compression. He subsequently underwent endoscopic retrograde cholangiopancreatography (ERCP) with stenting of the ampulla nine days later. The patient was discharged ten days post-ERCP with oral amoxicillin/clavulanic acid for polymicrobial coverage and follow-up with gastroenterology and IR for stent removal and drain maintenance.

Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor.

INTRODUCTION: Tumor-initiating cells (TIC) are being extensively studied for their role in tumor etiology, maintenance and resistance to treatment. The isolation of TICs has been limited by the scarcity of this population in the tissue of origin and because the molecular signatures that characterize these cells are not well understood. Herein, we describe the generation of TIC-like cell lines by ectopic expression of the OCT4 transcription factor (TF) in primary breast cell preparations. METHODS: OCT4 cDNA was over-expressed in four different primary human mammary epithelial (HMEC) breast cell preparations from reduction mammoplasty donors. OCT4-transduced breast cells (OTBCs) generated colonies (frequency ~0.01%) in self-renewal conditions (feeder cultures in human embryonic stem cell media). Differentiation assays, immunofluorescence, immunohistochemistry, and flow cytometry were performed to investigate the cell of origin of OTBCs. Serial dilutions of OTBCs were injected in nude mice to address their tumorigenic capabilities. Gene expression microarrays were performed in OTBCs, and the role of downstream targets of OCT4 in maintaining self-renewal was investigated by knock-down experiments. RESULTS: OTBCs overcame senescence, overexpressed telomerase, and down-regulated p16INK4A. In differentiation conditions, OTBCs generated populations of both myoepithelial and luminal cells at low frequency, suggesting that the cell of origin of some OTBCs was a bi-potent stem cell. Injection of OTBCs in nude mice generated poorly differentiated breast carcinomas with colonization capabilities. Gene expression microarrays of OTBC lines revealed a gene signature that was over-represented in the claudin-low molecular subtype of breast cancer. Lastly, siRNA-mediated knockdown of OCT4 or downstream embryonic targets of OCT4, such as NANOG and ZIC1, suppressed the ability of OTBCs to self-renew. CONCLUSIONS: Transduction of OCT4 in normal breast preparations led to the generation of cell lines possessing tumor-initiating and colonization capabilities. These cells developed high-grade, poorly differentiated breast carcinomas in nude mice. Genome-wide analysis of OTBCs outlined an embryonic TF circuitry that could be operative in TICs, resulting in up-regulation of oncogenes and loss of tumor suppressive functions. These OTBCs represent a patient-specific model system for the discovery of novel oncogenic targets in claudin-low tumors.