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Introduction: The perceptions of teaching faculty toward pregnant general surgery residents have been overlooked despite the daily interactions amongst these groups., Methods: A 32-question survey designed to measure general surgery teaching faculty perceptions toward pregnant residents was distributed electronically from March 2022 to April 2022 to general surgery teaching faculty in the United States. Descriptive statistics were used to characterize responses and differences in perceptions, and qualitative analysis identified recurring themes from free-text responses., Results: Among 163 respondents included in the final analysis, 58.5% were male and 41.5% were female. Despite 99.4% of surgeons feeling comfortable if a resident told them they were pregnant, 22.4% of surgeons disagreed that their institutions have supportive cultures toward pregnancy. Almost half (45.4%) have witnessed negative comments about pregnant residents and half (50.3%) believe that pregnant surgical residents are discriminated against by their coresidents. Nearly two-thirds of surgeons (64.8%) believe that someone should have a child whenever they wish during training. Given recent reports, 80.2% of surgeons recognized that female surgeons have increased risks of infertility and pregnancy complications. Recurring themes of normalizing pregnancy, improving policies, and creating a culture change were expressed., Conclusions: In this national survey, although there appears to be positive perceptions of pregnancy in surgical training amongst those surveyed, there is acknowledged necessity of further normalizing pregnancy and improving policies to better support pregnant residents. These data provide further evidence that though perceptions may be improving, changes are still needed to better support pregnancy during training., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of data regarding the knowledge and perceptions teaching faculty possess about breast pumping among general surgery residents despite breast pumping becoming more common during training. This study aimed to examine faculty knowledge and perceptions of breast pumping amongst general surgery residents., Methods: A 29-question survey measuring knowledge and perceptions about breast pumping was administered online to United States teaching faculty from March-April 2022. Descriptive statistics were used to characterize responses, Fisher's exact test was used to report differences in responses by surgeon sex and age, and qualitative analysis identified recurrent themes., Results: 156 responses were analyzed; 58.6% were male and 41.4% were female, and the majority (63.5%) were less than 50 years old. Nearly all (97.7%) women with children breast pumped, while 75.3% of men with children had partners who pumped. Men more often than women indicated "I don't know" when asked about frequency (24.7 vs. 7.9%, p = 0.041) and duration (25.0 vs. 9.5%, p = 0.007) of pumping. Nearly all surgeons are comfortable (97.4%) discussing lactation needs and support (98.1%) breast pumping, yet only two-thirds feel their institutions are supportive. Almost half (41.0%) of surgeons agreed that breast pumping does not impact operating room workflow. Recurring themes included normalizing breast pumping, creating change to better support residents, and communicating needs between all parties., Conclusions: Teaching faculty may have supportive perceptions about breast pumping, but knowledge gaps may hinder greater levels of support. Opportunities exist for increased faculty education, communication, and policies to better support breast pumping residents., (© 2023. The Author(s).)

Background: Imposter syndrome occurs when high-achieving individuals have a pervasive sense of self-doubt combined with fear of being exposed as a fraud, despite objective measures of success. This threatens mental health and well-being. The prevalence and severity of imposter syndrome has not been studied among general surgery residents on a large scale. The primary outcomes of this study were the prevalence and severity of imposter syndrome., Study Design: The Clance Impostor Phenomenon Scale was administered to residents at 6 academic general surgery residency programs. Multivariable analysis was performed to identify significant differences among groups and predictive characteristics of imposter syndrome., Results: One hundred and forty-four residents completed the assessment (response rate 46.6%; 47.2% were male). Only 22.9% had "none to mild" or "moderate" imposter syndrome. A majority (76%) had "significant" or "severe" imposter syndrome. There were no significant differences in mean scores among male and female residents (p = 0.69). White residents had a mean score of 71.3 and non-White residents had a mean score of 68.3 (p = 0.24). There was no significant difference between PGY1 to PGY5 or research residents (p = 0.72). There were no significant differences based on US Medical Licensing Examination or American Board of Surgery In-Service Training Examination scores (p = 0.18 and p = 0.37, respectively)., Conclusions: Imposter syndrome is prevalent among general surgery residents, with 76% of residents reporting either significant or severe imposter syndrome. There were no predictive characteristics based on demographics or academic achievement, suggesting that there is something either inherent to those choosing general surgery training or the general surgery training culture that leads to such substantive levels of imposter syndrome., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the implementation of a virtual, multi-institutional educational collaboration involving over 50 general surgery residency programs during the COVID-19 pandemic that enabled enhanced learning for surgical residents despite social-distancing requirements., Design: Description of Virginia Commonwealth University's virtual educational augmentation program and the development of a collaborative teaching network during the coronavirus pandemic., Setting: This collaboration was initiated by Virginia Commonwealth University's Department of Surgery, Richmond, VA, and grew to include general surgery residency programs from across the nation., Participants: General surgery residents and faculty from Departments of General Surgery were recruited locally via direct emails and nationally via the Association of Program Directors' listserv and Twitter. In total, 52 institutions participated from every part of the country., Results: A virtual, multi-institutional collaborative lecture series was initiated that grew to involve over 50 general surgery residency programs, allowing for daily didactics by experts in their fields during the initial surge of the COVID-19 pandemic, while maintaining social distancing and the provision of essential clinical care., Conclusion: A multi-institutional collaboration enabled continued didactic education during the coronavirus pandemic, vastly broadening the expertise, scope and variety available to residents, while decreasing burden on faculty. We believe this can serve as a framework for future multi-institutional collaborations that extend beyond the COVID-19 era., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The COVID-19 pandemic has disrupted graduate medical education, impacting Accreditation Council for Graduate Medical Education (ACGME)-mandated didactics. We aimed to study the utility of 2 methods of virtual learning: the daily National Surgery Resident Lecture Series (NSRLS), and weekly "SCORE School" educational webinars designed around the Surgical Council on Resident Education (SCORE) curriculum., Design and Setting: NSRLS: The National Surgery Resident Lecture Series was a daily virtual educational session initially led by faculty at an individual surgical residency program. Thirty-eight lectures were assessed for number of live viewings (March 23, 2020-May 15, 2020)., Score School: Attendance at eleven weekly SCORE educational webinars was characterized into live and asynchronous viewings (May 13, 2020-August 5, 2020). Each 1-hour live webinar was produced by SCORE on a Wednesday evening and featured nationally recognized surgeon educators using an online platform that allowed for audience interaction., Results: NSRLS: There were a mean of 71 live viewers per NSRLS session (range 19-118). Participation began to decline in the final 2 weeks as elective case volumes increased, but sessions remained well-attended., Score School: There were a range of 164-3889 live viewers per SCORE School session. Sessions have most commonly been viewed asynchronously (89.8% of viewings). Live viewership decreased as the academic year ended and then rebounded with the start of the new academic year (range 4.9%-27%). Overall, the eight webinars were viewed 11,135 times. Each webinar continues to be viewed a mean of 43 times a day (range 0-102). Overall, the eleven webinars have been viewed a total of 22,722 times., Conclusions: Virtual didactics aimed at surgical residents are feasible, well-attended (both live and recorded), and have high levels of viewer engagement. We have observed that careful coordination of timing and topics is ideal. The ability for asynchronous viewing is particularly important for attendance. As the COVID-19 pandemic continues to disrupt healthcare systems, training programs must continue to adapt to education via virtual platforms., Competing Interests: DECLARATION OF COMPETING INTEREST Drs. Joshi, Chahine, and Klingensmith, along with Mr. Hickey, Ms. Barret, and Ms. Bradley serve on the SCORE executive committee. Drs. Theodorou, Boyd, Stern, and Anand and Mr. Tilak have no disclosures to declare., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: After COVID-19 rendered in-person meetings for national societies impossible in the spring of 2020, the leadership of the Association of Program Directors in Surgery (APDS) innovated via a virtual format in order to hold its national meeting., Design: APDS leadership pre-emptively considered factors that would be important to attendees including cost, value, time, professional commitments, education, sharing of relevant and current information, and networking., Setting: The meeting was conducted using a variety of virtual formats including a web portal for entry, pre-ecorded poster and oral presentations on the APDS website, interactive panels via a web conferencing platform, and livestreaming., Participants: There were 298 registrants for the national meeting of the APDS, and 59 participants in the New Program Directors Workshop. The registrants and participants comprised medical students, residents, associate program directors, program directors, and others involved in surgical education nationally., Results: There was no significant difference detected for high levels of participant satisfaction between 2019 and 2020 for the following items: overall program rating, topics and content meeting stated objectives, relevant content to educational needs, educational format conducive to learning, and agreement that the program will improve competence, performance, communication skills, patient outcomes, or processes of care/healthcare system performance., Conclusions: A virtual format for a national society meeting can provide education, engagement, and community, and the lessons learned by the APDS in the process can be used by other societies for utilization and further improvement., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Non-designated preliminary (NDP) general surgery residents face the daunting challenge of obtaining a categorical residency position while undertaking the rigors of a general surgery residency. This additional application cycle represents a stressful time for these trainees and limited data exists to help guide applicants and program directors regarding the factors predictive of application success. While previous studies have focused solely on applicant related factors, no study to date has evaluated the effect of the residency program structure, institutional resources, or administrative support on these outcomes., Design/setting: A multicenter retrospective review of 10 general surgery residency programs over a 5-year period from 2014 to 2019 was performed. Applicant related information was compiled from NDP general surgery residents and the results of their attempted second application into a categorical position. Applicant factors including age, gender, standardized test scores (USMLE/ABSITE), and professional training were examined. Program and administrative structure including residency class size, number of NDP PGY-2 positions, number of assistant program directors and program director (PD) background were also examined. Primary success was defined as a NDP resident successfully obtaining a categorical position within general surgery or a surgical subspecialty. Secondary success was obtaining a categorical residency position in any field of medical practice other than surgery or a surgical subspecialty in the United States., Results: A total of 260 NDP trainees were evaluated with an average age of 29.1. Almost seventy percent of applicants were male, 40% graduated from a non-U.S. medical school and 24.2% required a visa to work in the United States. Thirty 4 percent of NDPs successfully obtained a categorical surgery position and an additional 35% obtained a categorical residency position in a nonsurgical field for an overall match success rate of 68.9%. Factors associated with primary success included ABSITE score (p < 0.001), US medical school graduation (p = 0.02), visa status (p = 0.03), presence of preliminary PGY-2 positions (p = 0.02), and PD professional development time (p = 0.004). Overall success was associated USMLE Step 1 scores (p = 0.02), number of approved chiefs (p = 0.03), presence of dedicated faculty researchers (p = 0.001), and PD professional development time (p < 0.001)., Conclusions: Applicant, program-related, and administrative factors all have a significant impact on the success of NDP general surgery residents in obtaining a categorical surgical position. Trainees should consider all of these factors when applying to NDP residencies and in approaching their second application cycle to maximize their likelihood of a successful match., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

We present a rare case of a focal perforation of the jejunum after a high-speed motor vehicle crash. A 60-year-old restrained rear seat passenger presented with severe abdominal pain. She was hemodynamically stable and underwent the traditional trauma workup. CT scan of the abdomen showed large-volume free intraperitoneal air and L4/L5 compression fractures. Given the peritoneal physical exam finding and free air on CT scan she was taken emergently to the operating room. Operative exploration revealed free intraperitoneal air upon entry into the abdominal cavity as well as murky fluid throughout the mid abdomen. A focal perforation was discovered on the antimesenteric surface of a segment of jejunum. The perforation was repaired primarily in two layers and the abdomen was closed. Postoperative course was uncomplicated. Antibiotics were continued for 4 days. Focal perforation of the small bowel from high-speed blunt trauma is a rare isolated injury. Close attention to physical exam and radiologic findings allows for early diagnosis and treatment of these injuries.

Background: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival., Methods: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay., Results: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity., Conclusion: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients., Level of Evidence: Diagnostic Test, level III.

Background: Medication errors account for the most common adverse events and a significant cause of mortality in the USA. The Joint Commission has required medication reconciliation since 2006. We aimed to survey the literature and determine the challenges and effectiveness of medication reconciliation in the trauma patient population., Materials and Methods: We conducted a systematic review of the literature to determine the effectiveness of medication reconciliation in trauma patients. English language articles were retrieved from PubMed/Medline, CINAHL, and Cochrane Review databases with search terms "trauma OR injury, AND medication reconciliation OR med rec OR med rek, AND effectiveness OR errors OR intervention OR improvements.", Results: The search resulted in 82 articles. After screening for relevance and duplicates, the 43 remaining were further reviewed, and only four articles, which presented results on medication reconciliation in 3041 trauma patients, were included. Two were retrospective and two were prospective. Two showed only 4% accuracy at time of admission with 48% of medication reconciliations having at least one medication discrepancy. There were major differences across the studies prohibiting comparative statistical analysis., Conclusions: Trauma medication reconciliation is important because of the potential for adverse outcomes given the emergent nature of the illness. The few articles published at this time on medication reconciliation in trauma suggest poor accuracy. Numerous strategies have been implemented in general medicine to improve its accuracy, but these have not yet been studied in trauma. This topic is an important but unrecognized area of research in this field., Competing Interests: N/A: systematic reviewN/A: systematic reviewThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: Resuscitative Thoracotomy or Emergency Department Thoracotomy (EDT) is a time-sensitive and potentially life-saving procedure. Yet, trainee experience with this procedure is often limited in both clinical and simulation settings. We sought to develop a high-fidelity EDT simulation module and assessment tool to facilitate trainee education., Design: Using the Kern model for curricular development, a group of expert trauma surgeons identified EDT as a high-stakes, low-frequency procedure. Task analysis identified 5 key steps of EDT: (1) opening chest/rib spreader utilization; (2) pericardiotomy/cardiac repair; (3) open cardiac massage; (4) clamping aorta; and (5) control of pulmonary hilum. A high-fidelity simulator with beating-heart technology was built. The previously validated Objective Structured Assessment of Technical Skills (OSATS) was adapted to create the "EDT-OSATS" which assessed performance along several domains: (1) Surgical technique (key steps); (2) general skills; and (3) global rating. A pilot test was performed to compare board-certified trauma surgeons (i.e., Experts) with categorical general surgery interns (i.e., Novices). Each subject received preparatory materials, completed a presimulation quiz, performed a videotaped procedure on the EDT simulator, and completed a postmodule survey. Two independent raters scored performances using the EDT-OSATS. Groups were compared in descriptive and unadjusted analyses. We hypothesized that our EDT simulation module would distinguish between expert vs novice performance and improve trainee confidence., Setting: Simulation laboratory at Massachusetts General Hospital in Boston, MA., Participants: Trauma surgeons (Experts, n = 6) and categorical general surgery interns (Novices, n = 8)., Results: Experts scored significantly higher than Novices on nearly all components of the EDT-OSATS, including: (1) surgical technique: pericardiotomy (4.2 vs 3.4, p = 0.040), cardiac massage (3.6 vs 2.4, p = 0.028), clamping aorta (4.1 vs 3.3, p = 0.035), control of pulmonary hilum (4.8 vs 3.4, p < 0.001); (2) general skills: time/motion (4.1 vs 2.9, p = 0.011), knowledge and handling of instruments (4.3 vs 3.1, p = 0.004), and (3) global rating (3.9 vs 2.9, p = 0.026). There was no statistical difference between groups on opening chest/rib spreader utilization (3.8 vs 3.3, p = 0.352) or procedure time (204sec vs 227sec, p = 0.401), though Experts scored numerically higher than Novices on every measure. Novices reported significantly increased confidence after the simulation (3.1 vs 1.4, p = 0.001). Ninety-three percent (13/14) of participants found the simulator realistic., Conclusions: Our novel high-fidelity beating-heart EDT simulator is realistic and improves trainee confidence in this low-frequency, high-stakes emergency procedure. The EDT-OSATS tool differentiates between performances of experienced surgeons vs novice trainees on the beating-heart simulator. This training module and accompanying assessment instrument hold promise as a learning tool for clinicians who may perform emergency department thoracotomy., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Trauma is a major problem in the United States. Mortality from trauma is the number one cause of death under the age of 45 in the United States and is the third leading cause of death for all age groups. There are approximately 200,000 deaths per year due to trauma in the United States at a cost of over $671 billion in combined healthcare costs and lost productivity. Unsurprisingly, trauma accounts for approximately 30% of all life-years lost in the United States. Due to immense development of trauma systems, a large majority of trauma patients survive the injury, but then go on to die from complications arising from the injury. These complications are marked by early and significant metabolic changes accompanied by inflammatory responses that lead to progressive organ failure and, ultimately, death. Early resuscitative and surgical interventions followed by close monitoring to identify and rescue treatment failures are key to successful outcomes. Currently, the adequacy of resuscitation is measured using vital signs, noninvasive methods such as bedside echocardiography or stroke volume variation, and other laboratory endpoints of resuscitation, such as lactate and base deficit. However, these methods may be too crude to understand cellular and subcellular changes that may be occurring in trauma patients. Better diagnostic and therapeutic markers are needed to assess the adequacy of interventions and monitor responses at a cellular and subcellular level and inform clinical decision-making before complications are clinically apparent. The developing field of metabolomics holds great promise in the identification and application of biochemical markers toward the clinical decision-making process.

Background: Subclavian and axillary artery injuries are uncommon. In addition to many open vascular repairs, endovascular techniques are used for definitive repair or vascular control of these anatomically challenging injuries. The aim of this study was to determine the relative roles of endovascular and open techniques in the management of subclavian and axillary artery injuries comparing hospital outcomes, and long-term limb viability., Methods: A multicenter, retrospective review of patients with subclavian or axillary artery injuries from January 1, 2004, to December 31, 2014, was completed at 11 participating Western Trauma Association institutions. Statistical analysis included χ, t-tests, and Cochran-Armitage trend tests. A p value less than 0.05 was significant., Results: Two hundred twenty-three patients were included; mean age was 36 years, 84% were men. An increase in computed tomography angiography and decrease in conventional angiography was observed over time (p = 0.018). There were 120 subclavian and 119 axillary artery injuries. Procedure type was associated with injury grade (p < 0.001). Open operations were performed in 135 (61%) patients, including 93% of greater than 50% circumference lacerations and 83% of vessel transections. Endovascular repairs were performed in 38 (17%) patients; most frequently for pseudoaneurysms. Fourteen (6%) patients underwent a hybrid procedure. Use of endovascular versus open procedures did not increase over the duration of the study (p = 0.248). In-hospital mortality rate was 10%. Graft or stent thrombosis occurred in 7% and graft or stent infection occurred in 3% of patients. Mean follow-up was 1.6 ± 2.4 years (n = 150). Limb salvage was achieved in 216 (97%) patients., Conclusion: The management of subclavian and axillary artery injuries still requires a wide variety of open exposures and procedures, especially for the control of active hemorrhage from more than 50% vessel lacerations and transections. Endovascular repairs were used most often for pseudoaneurysms. Low early complication rates and limb salvage rates of 97% were observed after open and endovascular repairs., Level of Evidence: Prognostic/epidemiologic, level IV.

Purpose: The National Board of Medical Examiners' Clinical Science Subject Examinations are a component used by most U.S. medical schools to determine clerkship grades. The purpose of this study was to examine the validity of this practice., Method: This was a retrospective cohort study of medical students at the Virginia Commonwealth University School of Medicine who completed clerkships in 2012 through 2014. Linear regression was used to determine how well United States Medical Licensing Examination Step 1 scores predicted Subject Examination scores in seven clerkships. The authors then substituted each student's Subject Examination standard scores with his or her Step 1 standard score. Clerkship grades based on the Step 1 substitution were compared with actual grades with the Wilcoxon rank test., Results: A total of 2,777 Subject Examination scores from 432 students were included in the analysis. Step 1 scores significantly predicted between 23% and 44% of the variance in Subject Examination scores, P < .001 for all clerkship regression equations. Mean differences between expected and actual Subject Examination scores were small (≤ 0.2 points). There was a match between 73% of Step 1 substituted final clerkship grades and actual final clerkship grades., Conclusions: The results of this study suggest that performance on Step 1 can be used to identify and counsel students at risk for poor performance on the Subject Examinations. In addition, these findings call into the question the validity of using scores from Subject Examinations as a high-stakes assessment of learning in individual clerkships.

Background: Scores from the NBME Subject Examination in Surgery (Surgery Shelf) positively correlate with United States Medical Licensing Examination Step 1 (Step 1). Based on this relationship, the authors evaluated the predictive value of Step 1 on the Surgery Shelf., Methods: Surgery Shelf standard scores were substituted for Step 1 standard scores for 395 students in 2012-2014 at one medical school. Linear regression was used to determine how well Step 1 scores predicted Surgery Shelf scores. Percent match between original (with Shelf) and modified (with Step 1) clerkship grades were computed., Results: Step 1 scores significantly predicted Surgery Shelf scores, R 2  = 0.42, P < 0.001. For every point increase in Step 1, a Surgery Shelf score increased by 0.30 points. Seventy-seven percent of original grades matched the modified grades., Conclusion: Replacing Surgery Shelf scores with Step 1 scores did not have an effect on the majority of final clerkship grades. This observation raises concern over use of Surgery Shelf scores as a measure of knowledge obtained during the Surgery clerkship., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Acute gangrenous cholecystitis (AGC) is a medical emergency that carries high morbidity. The objective of this study is to define risk factors for this disease., Methods: A retrospective review of patients who underwent cholecystectomy while admitted to the Acute Care Surgery Service from January 2009 to April 2014 was performed. Specimen reports were evaluated to identify patients with AGC and cholecystitis without necrosis (CN). Preoperative factors as well as outcomes were compared between the groups., Results: A total of 483 patents underwent cholecystectomy. Four hundred fifty-nine patients were found to have CN and 24 patients were found to have AGC. Pre-existent factors such as diabetes, coronary artery disease, and systemic inflammatory response syndrome predicted AGC on a logistic regression. Patients with AGS were also more commonly older, male, and had a higher preoperative bilirubin. Mortality was significantly higher in patients with AGC (12.5% vs .9%, P = .003)., Conclusions: AGC carries an increased mortality rate compared with CN. Older patients with diabetes, coronary artery disease, and elevated bilirubin should be suspected of having AGC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Limited transthoracic echocardiography (LTTE) has been introduced as a hemodynamic tool for trauma patients. The aim of this study was to evaluate the utility of LTTE during the evaluation of nonsurviving patients who presented to the trauma bay with traumatic cardiac arrest., Methods: Approval by the Institutional Review Board was obtained. All nonsurviving patients with traumatic cardiac arrest who reached the trauma bay were evaluated retrospectively for 1 year. Comparisons between groups of patients in whom LTTE was performed as part of the resuscitation effort and those in whom it was not performed were conducted., Results: From January 2012 to January 2013, 37 patients did not survive traumatic cardiac arrest while in the trauma bay: 14 in the LTTE group and 23 in the non-LTTE group. When comparing the LTTE and non-LTTE groups, both were similar in sex distribution (LTTE, 86% male; non-LTTE, 74% male; P = .68), age (34.8 versus 24.1 years; P= .55), Injury Severity Score (41.0 versus 38.2; P= .48), and percentage of penetrating trauma (21.6% versus 21.7%; P = .29). Compared with the non-LTTE group, the LTTE group spent significantly less time in the trauma bay (13.7 versus 37.9 minutes; P = .01), received fewer blood products (7.1% versus 31.2%; P = .789), and were less likely to undergo nontherapeutic thoracotomy in the emergency department (7.14% versus 39.1%; P < .05). The non-LTTE group had a mean of $3040.50 in hospital costs, compared with the mean for the LTTE group of $1871.60 (P = .0054)., Conclusions: In this study, image-guided resuscitation with LTTE decreased the time in the trauma bay and avoided nontherapeutic thoracotomy in nonsurviving trauma patients. Limited TTE could improve the use of health care resources in patients with traumatic cardiac arrest., (© 2014 by the American Institute of Ultrasound in Medicine.)

Introduction: Endovascular technology during the past decade has introduced innovative strategies to manage vascular trauma. The purpose of this study was to evaluate the current use catheter-based endovascular damage-control techniques (CDET) in North, Central, and South America., Methods: A survey was sent to the presidents of local societies in Latin America, members of the board, and past presidents of the Pan-American Trauma Society. The survey was sent using the Research Electronic Data Capture collection tool., Results: A total of 67 surveys were sent with an 85 % response rate. Surgeons from 15 countries participated in the survey. All of the centers in North America had capabilities to perform these procedures. In none of these centers, however, were they performed by trauma and acute care surgeons. In Central and South America, 64 % of the surgeons responded that they have an interventional radiology service, and in 56 % of the cases, trauma and acute care surgeons were already performing CDET. Eight-eight percent of those surveyed thought that the addition of CDET to trauma would improve patient care; 86 % would be interested in further training in this technique if such programs were available. Finally, 68 % thought that the addition of CDET would help the field of acute care surgery and trauma financially., Conclusions: CDET is being performed already by trauma and acute care surgeons in Latin American countries. More research is necessary to evaluate the role of the trauma surgeon in the endovascular suite as well as training requirements.

Background: We hypothesize that limited transthoracic echocardiogram (LTTE) is a useful tool to guide therapy during the initial phase of resuscitation in trauma patients., Methods: All highest-level alert patients with at least one measurement of systolic blood pressure less than 100 mm Hg, a mean arterial pressure less than 60 mm Hg, and/or a heart rate greater than 120 beats per minute who arrived to the trauma bay (TB) were randomized to have either LTTE performed (LTTEp) or not performed (non-LTTE) as part of their initial evaluation. Images were stored, and results were reported regarding contractility (good vs. poor), fluid status (empty inferior vena cava [hypovolemic] vs. full inferior vena cava [not hypovolemic]), and pericardial effusion (present vs. absent). Time from TB to operating room, intravenous fluid administration, blood product requirement, intensive care unit admission, and mortality were examined in both groups., Results: A total of 240 patients were randomized. Twenty-five patients were excluded since they died upon arrival to the TB, leaving 215 patients in the study. Ninety-two patients were in the LTTEp group with 123 patients in the non-LTTE group. The LTTEp and non-LTTE groups were similar in age (38 years vs. 38.8 years, p = 0.75), Injury Severity Score (ISS) (19.2 vs. 19.0, p = 0.94), Revised Trauma Score (RTS) (5.5 vs. 6.0, p = 0.09), lactate (4.2 vs. 3.6, p = 0.14), and mechanism of injury (p = 0.44). Strikingly, LTTEp had significantly less intravenous fluid than non-LTTE patients (1.5 L vs. 2.5 L, p < 0.0001), less time from TB to operating room (35.6 minutes vs. 79.1 min, p = 0.0006), higher rate of intensive care unit admission (80.4% vs. 67.2%, p = 0.04), and a lower mortality rate (11% vs. 19.5%, p = 0.09). Mortality differences were particularly evident in the traumatic brain injury patients (14.7% in LTTEp vs. 39.5% in non-LTTE, p = 0.03)., Conclusion: LTTE is a useful guide for therapy in hypotensive trauma patients during the early phase of resuscitation., Level of Evidence: Therapeutic study, level II.

Objective: The aim of this study is to evaluate the impact of obesity on patient outcomes after emergency surgery., Methods: A list of all patients undergoing emergent general surgical procedures during the 12 months ending in July 2012 was obtained from the operating room log. A chart review was performed to obtain the following data: patient characteristics (age, gender, BMI, and preexisting comorbidities), indication for surgery, and outcomes (pulmonary embolus (PE), deep venous thrombosis (DVT), respiratory failure, ICU admission, wound infection, pneumonia, and mortality). Obesity was defined as a BMI over 25. Comparisons of outcomes between obese and nonobese patients were evaluated using Fischer's exact test. Predictors of mortality were evaluated using logistic regression., Results: 341 patients were identified during the study period. 202 (59%) were obese. Both groups were similar in age (48 for obese versus 47 for nonobese, P = 0.42). Obese patients had an increased incidence of diabetes, (27% versus 7%, P < 0.05), hypertension (52% versus 34%, P < 0.05), and sleep apnea (0% versus 5%, P < 0.05). There was a statistically significant increased incidence of postoperative wound infection (obese 9.9% versus nonobese 4.3%, P < 0.05) and ICU admission (obese 58% versus nonobese 42%, P = 0.01) among the obese patients. Obesity alone was not shown to be a significant risk factor for mortality., Conclusions: A higher BMI is not an independent predictor of mortality after emergency surgery. Obese patients are at a higher risk of developing wound infections and requiring ICU admission after emergent general surgical procedure.

Background: Limited transthoracic echocardiogram (LTTE) has been introduced as a technique to direct resuscitation in intensive care unit (ICU) patients. Our hypothesis is that LTTE can provide meaningful information to guide therapy for hypotension in the trauma bay., Methods: LTTE was performed on hypotensive patients in the trauma bay. Views obtained included parasternal long and short, apical, and subxyphoid. Results were reported regarding contractility (good vs. poor), fluid status (flat inferior vena cava [hypovolemia] vs. fat inferior vena cava [euvolemia]), and pericardial effusion (present vs. absent). Need for surgery, ICU admission, Focused Assessment with Sonography for Trauma examination results, and change in therapy as a consequence of LTTE findings were examined. Data were collected prospectively to evaluate the utility of this test., Results: A total of 148 LTTEs were performed in consecutive patients from January to December 2011. Mean age was 46 years. Admission diagnosis was 80% blunt trauma, 16% penetrating trauma, and 4% burn. Subxyphoid window was obtained in all patients. Parasternal and apical windows were obtained in 96.5% and 11%, respectively. Flat inferior vena cava was associated with an increased incidence of ICU admission (p < 0.0076) and therapeutic operation (p < 0.0001). Of the 148 patients, 27 (18%) had LTTE results indicating euvolemia. The diagnosis in these cases was head injury (n = 14), heart dysfunction (n = 5), spinal shock (n = 4), pulmonary embolism (n = 3), and stroke (n = 1). Of the patients, 121 had LTTE results indicating hypovolemia. Twenty-eight hypovolemic patients had a negative or inconclusive Focused Assessment with Sonography for Trauma examination finding (n = 18 penetrating, n = 10 blunt), with 60% having blood in the abdomen confirmed by surgical exploration or computed tomographic scan. Therapy was modified as a result of LTTE in 41% of cases. Strikingly, in patients older than 65 years, LTTE changed therapy in 96% of cases., Conclusion: LTTE is a useful tool to guide therapy in hypotensive patients in the trauma bay., Level of Evidence: Diagnostic study, level III.

Flat inferior vena cava (IVC) on ultrasound examination has been shown to correlate with hypovolemic status. We hypothesize that a flat IVC on limited echocardiogram (LTTE) performed in the emergency room (ER) correlates with poor prognosis in acutely ill surgical patients. We conducted a retrospective review of all patients undergoing LTTE in the ER from September 2010 until June 2011. IVC diameter was estimated by subxiphoid window. Flat IVC was defined as diameter less than 2 cm. Fat IVC was defined as diameter greater than 2 cm. Need for intensive care unit admission, blood transfusion requirement, mortality, and need for emergent operation between patients with flat versus Fat IVC were compared. One hundred one hypotensive patients had LTTE performed in the ER. Average age was 38 years. Admission diagnosis was blunt trauma (n = 80), penetrating trauma (n = 13), acute care surgery pathology (n = 7), and burn (n = 1). Seventy-four patients had flat IVC on initial LTTE. Compared with those with fat IVC, flat patients were found have higher rates of intensive care unit admission (51.3 vs 14.8%; P = 0.001), blood transfusion requirement (12.2 vs 3.7%), and mortality (13.5 vs 3.7%). This population also underwent emergent surgery on hospital Day 1 more often (16.2 vs 0%; P = 0.033). Initial flat IVC on LTTE is an indicator of hypovolemia and a predictor of poor outcome.

Background: The use of prophylactic antibiotics in penetrating abdominal trauma has resulted in decreased infection rates. The Eastern Association for the Surgery of Trauma (EAST) first published its practice management guidelines (PMGs) for the use of prophylactic antibiotics in penetrating abdominal trauma in 1998. During the next decade, several new prospective studies were published on this topic. In addition, the practice of damage control laparotomy became widely used, and additional questions arose as to the role of prophylactic antibiotics in this setting. Thus, the EAST Practice Management Guidelines Committee set out to update the original PMG., Methods: A search of the National Library of Medicine and the National Institutes of Health MEDLINE databases was performed using PubMed (www.pubmed.gov) and specific key words. The search retrieved English language articles regarding the use of antibiotics in penetrating abdominal trauma published from 1973 to 2011. The topics investigated were the need for perioperative antibiotics, the duration of antibiotic therapy, the dose of antibiotics in patients presenting in hemorrhagic shock, and the appropriate duration of antibiotic therapy in the setting of damage control laparotomy., Results: Forty-four articles were identified for inclusion in this review., Conclusion: There is evidence to support a Level I recommendation that prophylactic antibiotics should only be administered for 24 hours in the presence of a hollow viscus injury. In addition, there are no data to support continuing prophylactic antibiotics longer than 24 hours in damage control laparotomy.

Inferior vena cava (IVC) diameter change on limited transthoracic echocardiogram (LTTE) can provide a useful guide of fluid status evaluation in critically ill patients. Institutional review board approval was obtained. Prospective evaluation of hemodynamic status was performed in hypotensive patients via LTTE. Images were obtained using an ultrasound machine without M-mode capability. Qualitative assessment of the IVC was obtained via subxyphoid window. FLAT IVC was defined as diameter less than 2 cm and FAT IVC when the vein was equal or larger than 2 cm. Collapsibility was assessed by observing respiratory variation of the vessel. Lactate was measured before and after therapy was initiated. A follow-up LTTE was obtained after fluid challenge. A total of 108 LTTE were performed. Patients' age ranged from 18 to 89 years with an average of 53. Admission diagnosis was blunt trauma in 66 patients, penetrating trauma in 17, whereas 25 had nontraumatic intra-abdominal emergency. Sixty-nine patients were receiving mechanical ventilation at time of LTTE. Seventy-three patients had a FLAT IVC, and received fluid challenge as therapy. All patients had a change in IVC volume from "FLAT" to "FAT" after the fluid challenge. Seventy-one patients (97%) had resolution of hypotension after the first fluid challenge. Two patients had persistent hypotension and received a second fluid challenge. Follow-up LTTE demonstrated a FAT IVC and lack of collapsibility. Lactate decreased in all 73 patients after therapy guided by LTTE (P < 0.00001) Evaluation of the IVC diameter via LTTE offers a rapid, non invasive way to evaluate fluid status in critically ill patients.

The factors contributing to the development of pneumothorax after removal of chest tube thoracostomy are not fully understood. We hypothesized that development of post pull pneumothorax (PPP) after chest tube removal would be significantly lower in those patients with thicker chest walls, due to the "protective" layer of adipose tissue. All patients on our trauma service who underwent chest tube thoracostomy from July 2010 to February 2011 were retrospectively reviewed. Patient age, mechanism of trauma, and chest Abbreviated Injury Scale score were analyzed. Thoracic CTs were reviewed to ascertain chest wall thickness (CW). Thickness was measured at the level of the nipple at the midaxillary line, as perpendicular distance between skin and pleural cavity. Chest X-ray reports from immediately prior and after chest tube removal were reviewed for interval development of PPP. Data are presented as average ± standard deviation. Ninety-one chest tubes were inserted into 81 patients. Patients who died before chest tube removal (n = 11), or those without thoracic CT scans (n = 13) were excluded. PPP occurred in 29.9 per cent of chest tube removals (20/67). When PPP was encountered, repeat chest tube was necessary in 20 per cent of cases (4/20). After univariate analysis, younger age, penetrating mechanism, and thin chest wall were found to be significant risk factors for development of PPP. Chest Abbreviated Injury Scale score was similar in both groups. Logistic regression showed only chest wall thickness to be an independent risk factor for development of PPP.

Academic surgery programs need to offer avenues not only to increase recruitment of women, but also to provide support so women can stay in the surgical field successfully. Virginia Commonwealth University has served to enable the growth of women surgeons in their careers. This article reviews the aspects in which this institution has provided with the necessary support for career and personal growth.

Background: Limited transthoracic echocardiogram (LTTE) represents an attractive alternative to formal transthoracic echocardiogram (TTE), because it does not require an echocardiogram machine. Our hypothesis is that trauma attendings can learn LTTE effectively with minimal training., Methods: Seven attendings at a Level I trauma center received didactic and hands-on training in LTTE and performed this test on hypotensive patients to evaluate for contractility, fluid status, and pericardial effusion. Therapy to improve perfusion (administration of fluids, ionotropes, or vasopressors) was guided by LTTE findings. Perfusion status was determined by serum lactate level before and 6 hours after LTTE. Findings were compared with cardiology-performed TTE., Results: Range of postresidency training was 1 year to 29 years. LTTE teaching entailed 70 minutes of didactics and 25 minutes of hands-on. In all, 52 LTTEs were performed; two patients were excluded due to blunt trauma arrest. Age ranged from 22 years to 89 years with an average of 55 years. Admission diagnosis was blunt trauma (n = 34), penetrating trauma (n = 3), and intra-abdominal sepsis (n = 13). Average time for LTTE was 4 minutes 38 seconds. Cardiology-performed TTE was obtained in all patients, and correlation with LTTE was 100%. A total of 37 patients received intravenous fluid, 9 received vasopressors, and 4 received ionotropes as guided by LTTE findings, with lactate reduction in all patients (p < 0.00001). Attendings scored a mean of 88% in a written test after training., Conclusions: Trauma attendings can successfully learn LTTE with minimal training and use the technique as a resuscitation tool in the hypotensive patient.

Background: Biliary leak after severe hepatic trauma is a complex problem requiring multidisciplinary care. We report on our experience with endoscopic management of posttraumatic bile leaks and clarify the role of endoscopic retrograde cholangiopancreatography (ERCP)., Methods: A retrospective analysis was performed on all patients who sustained liver injury and underwent ERCP from September 2003 to September 2009. Patients who had associated biliary leak were identified. Patient demographics, injury characteristics, liver operations, endoscopic treatment, and success of endoscopic intervention were reviewed. Liver injury was managed in an interdisciplinary fashion, including immediate or delayed operation or angiography or both for primary or adjunctive hemostasis. ERCP with stenting and sphincterotomy was used to treat biliary fistulae. Sequelae of liver injury including biloma or other perihepatic fluid collection were also managed by computed tomography scan-guided or ultrasound-guided drainage., Results: A total of 26 patients underwent ERCP for the management of biliary fistula as a result of severe hepatic trauma. There were 14 (54%) blunt injuries. In every patient (100%), ERCP with stenting and sphincterotomy was successful in controlling bile leak. All patients eventually had removal of stents and drains, with resolution of leak. Two patients had concomitant treatment of associated pancreatic ductal injury., Conclusion: ERCP is useful as both a diagnostic and therapeutic tool for the safe treatment of biliary ductal injuries after severe liver trauma and should be part of a multidisciplinary treatment algorithm.

The initial management of intra-abdominal hypertension (IAH) is medical measures to reduce intra-abdominal pressure (IAP). These, in combination with percutaneous drainage of peritoneal free fluid, may serve to reduce IAH. If these measures fail, surgical decompression of the abdomen by laparotomy is necessary to control the IAP, search for and treat inciting factors, and reduce the hypertension. The abdomen is usually left open with temporary abdominal closure techniques. Surgical decompression of IAH associated with acute pancreatitis or secondary abdominal compartment syndrome has other surgical options besides a complete celiotomy. Attention to detail in surgical technique and postoperative care is essential for optimal outcome.

Background: A transthoracic focused rapid echocardiographic evaluation (FREE) was developed to answer specific questions about treatment direction regarding the use of fluid versus ionotropes in trauma patients. Our objective was to evaluate the clinical utility of the information obtained by this diagnostic test., Methods: The FREE was performed by an ultrasonographer or an intensivist and interpreted by a surgical intensivist using a full service portable echo machine (Vivid i; GE Healthcare). The clinical team ordering the examination was surveyed before and after the test was performed., Results: During a 9-month study period, the FREE was performed in 53 patients admitted to our trauma critical care units. In 80% of patients, an estimated ejection fraction was obtained. Moderate and severe left ventricular dysfunction was diagnosed in 56% of patients, and right heart dysfunction was found in 25% of the patients. Inferior vena cava (IVC) diameter and IVC respiratory variation was visualized in 80% of patients. In 87% (46 of 53), the FREE was able to answer the clinical question asked by the primary team. Strikingly, in 54% of patients, the plan of care was modified as a result of the FREE examination., Conclusions: IVC diameter and IVC respiratory variation was able to be obtained in the majority of cases, giving an estimate of fluid status. Estimation of ejection fraction was useful in guiding the treatment plan regarding the requirement of fluid boluses versus ionotropic support. We conclude that the FREE can provide meaningful data in difficult to image critically ill trauma patients.

Necrotizing enterocolitis (NEC) is a common and often fatal inflammatory disorder affecting preterm infants that develops upon interaction of indigenous bacteria with the premature intestine. We now demonstrate that the developing mouse intestine shows reciprocal patterns of expression of TLR4 and TLR9, the receptor for bacterial DNA (CpG-DNA). Using a novel ultrasound-guided in utero injection system, we administered LPS directly into the stomachs of early and late gestation fetuses to induce TLR4 signaling and demonstrated that TLR4-mediated signaling within the developing intestine follows its expression pattern. Murine and human NEC were associated with increased intestinal TLR4 and decreased TLR9 expression, suggesting that reciprocal TLR4 and TLR9 signaling may occur in the pathogenesis of NEC. Enteral administration of adenovirus expressing mutant TLR4 to neonatal mice reduced the severity of NEC and increased TLR9 expression within the intestine. Activation of TLR9 with CpG-DNA inhibited LPS-mediated TLR4 signaling in enterocytes in a mechanism dependent upon the inhibitory molecule IRAK-M. Strikingly, TLR9 activation with CpG-DNA significantly reduced NEC severity, whereas TLR9-deficient mice exhibited increased NEC severity. Thus, the reciprocal nature of TLR4 and TLR9 signaling within the neonatal intestine plays a role in the development of NEC and provides novel therapeutic approaches to this disease.

The pathways that lead to the internalization of pathogens via phagocytosis remain incompletely understood. We now demonstrate a previously unrecognized role for the gap junction protein connexin43 (Cx43) in the regulation of phagocytosis by macrophages and in the host response to bacterial infection of the peritoneal cavity. Primary and cultured macrophages were found to express Cx43, which localized to the phagosome upon the internalization of IgG-opsonized particles. The inhibition of Cx43 using small interfering RNA or by obtaining macrophages from Cx43 heterozygous or knockout mice resulted in significantly impaired phagocytosis, while transfection of Cx43 into Fc-receptor expressing HeLa cells, which do not express endogenous Cx43, conferred the ability of these cells to undergo phagocytosis. Infection of macrophages with adenoviruses expressing wild-type Cx43 restored phagocytic ability in macrophages from Cx43 heterozygous or deficient mice, while infection with viruses that expressed mutant Cx43 had no effect. In understanding the mechanisms involved, Cx43 was required for RhoA-dependent actin cup formation under adherent particles, and transfection with constitutively active RhoA restored a phagocytic phenotype after Cx43 inactivation. Remarkably, mortality was significantly increased in a mouse model of bacterial peritonitis after Cx43 inhibition and in Cx43 heterozygous mice compared with untreated and wild-type counterparts. These findings reveal a novel role for Cx43 in the regulation of phagocytosis and rearrangement of the F-actin cytoskeleton, and they implicate Cx43 in the regulation of the host response to microbial infection.

Background: The early signaling events in the development of necrotizing enterocolitis (NEC) remain undefined. We have recently shown that the endotoxin (lipopolysaccharide [LPS]) receptor toll-like receptor 4 (TLR4) on enterocytes is critical in the pathogenesis of experimental NEC. Given that the membrane receptor CD14 is known to facilitate the activation of TLR4, we now hypothesize that endotoxemia induces an early upregulation of CD14 in enterocytes and that this participates in the early intestinal inflammatory response in the development of NEC., Methods: IEC-6 enterocytes were treated with LPS (50 microg/mL), and the subcellular localization of CD14 and TLR4 was assessed by confocal microscopy. C57/Bl6 or CD14-/- mice were treated with LPS (5 mg/kg), whereas experimental NEC was induced using a combination of gavage formula feeding and intermittent hypoxia. CD14 expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reverse transcriptase-polymerase chain reaction, and interleukin 6 was quantified by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction., Results: Exposure of IEC-6 enterocytes to LPS led to an initial, transient increase in CD14 expression. The early increase in CD14 expression was associated with internalization of CD14 to a perinuclear compartment where increased colocalization with TLR4 was noted. The in vivo significance of these findings is suggested as treatment of mice with LPS led to an early increase in CD14 expression in the intestinal mucosa, whereas the persistent endotoxemia of experimental NEC was associated with decreased CD14 expression within enterocytes., Conclusions: LPS signaling in the enterocyte is marked by an early, transient increase in expression of CD14 and redistribution of the receptor. This process may contribute to the early activation of the intestinal inflammatory response that is observed in the development of NEC.

Emerging evidence suggests that the innate immune system, comprised of Toll-like receptors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflammation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen recognition and bacterial clearance by leukocytes, their dysregulation and unique signaling effects within intestinal epithelia in the setting of inflammation may have devastating consequences. For instance, activation of TLR4 in enterocytes leads to an inhibition of enterocyte migration and proliferation as well as the induction of enterocyte apoptosis-factors that would be expected to promote intestinal injury while inhibiting intestinal repair. TLR signaling has been shown to be abnormal in several intestinal inflammatory diseases, including Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. This review serves to examine the evidence regarding the patterns of expression and signaling of TLRs in the intestinal mucosa at basal levels and during physiologic stressors to gain insights into the pathogenesis of intestinal inflammation. We conclude that the data reviewed suggest that epithelial TLR signaling-acting in concert with TLR signaling by leukocytes-participates in the development of intestinal inflammation. We further conclude that the evidence reviewed provides a rationale for the development of novel, epithelial-specific, TLR-based agents in the management of diseases of intestinal inflammation.

Enterocytes exist in close association with tissue macrophages, whose activation during inflammatory processes leads to the release of nitric oxide (NO). Repair from mucosal injury requires the migration of enterocytes into the mucosal defect, a process that requires connexin43 (Cx43)-mediated gap junction communication between adjacent enterocytes. Enterocyte migration is inhibited during inflammatory conditions including necrotizing enterocolitis, in part, through impaired gap junction communication. We now hypothesize that activated macrophages inhibit gap junctions of adjacent enterocytes and seek to determine whether NO release from macrophages was involved. Using a coculture system of enterocytes and macrophages, we now demonstrate that "activation" of macrophages with lipopolysaccharide and interferon reduces the phosphorylation of Cx43 in adjacent enterocytes, an event known to inhibit gap junction communication. The effects of macrophages on enterocyte gap junctions could be reversed by treatment of macrophages with the inducible nitric oxide synthase (iNOS) inhibitor l-Lysine omega-acetamidine hydrochloride (l-NIL) and by incubation with macrophages from iNOS(-/-) mice, implicating NO in the process. Activated macrophages also caused a NO-dependent redistribution of connexin43 in adjacent enterocytes from the cell surface to an intracellular location, further suggesting NO release may inhibit gap junction function. Treatment of enterocytes with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) markedly inhibited gap junction communication as determined using single cell microinjection of the gap junction tracer Lucifer yellow. Strikingly, activated macrophages inhibited enterocyte migration into a scraped wound, which was reversed by l-NIL pretreatment. These results implicate enterocyte gap junctions as a target of the NO-mediated effects of macrophages during intestinal inflammation, particularly where enterocyte migration is impaired.

Phagocytosis is the process by which microbial pathogens are engulfed by macrophages and neutrophils and represents the first line of defense against bacterial infection. The importance of phagocytosis for bacterial clearance is of particular relevance to systemic inflammatory diseases, which are associated with the development of hypoxia, yet the precise effects of hypoxia on phagocytosis remain largely unexplored. We now hypothesize that hypoxia inhibits phagocytosis in macrophages and sought to determine the mechanisms involved. Despite our initial prediction, hypoxia significantly increased the phagocytosis rate of particles in vitro by RAW264.7 and primary peritoneal macrophages and increased phagocytosis of labeled bacteria in vivo by hypoxic mice compared with normoxic controls. In understanding the mechanisms involved, hypoxia caused no changes in RhoA-GTPase signaling but increased the phosphorylation of p38-MAPK significantly. Inhibition of p38 reversed the effects of hypoxia on phagocytosis, suggesting a role for p38 in the hypoxic regulation of phagocytosis. Hypoxia also significantly increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in macrophages, which was reversed after p38 inhibition, suggesting a link between p38 activation and HIF-1alpha expression. It is striking that small interfering RNA knockdown of HIF-1alpha reversed the effects of hypoxia on phagocytosis, and overexpression of HIF-1alpha caused a surprising increase in phagocytosis compared with nontransfected controls, demonstrating a specific role for HIF-1alpha in the regulation of phagocytosis. These data indicate that hypoxia enhances phagocytosis in macrophages in a HIF-1alpha-dependent manner and shed light on an important role for HIF-1alpha in host defense.

Background: Peritoneal sepsis is a significant cause of mortality in infants with necrotizing enterocolitis, caused in part by impaired bacterial clearance. Recent studies have identified toll-like receptor-4 (TLR4) as a receptor for endotoxin (lipopolysaccharide [LPS]). We hypothesized that TLR4 regulates bacterial clearance from the peritoneal cavity and sought to investigate whether macrophage phagocytosis was involved., Methods: Peritoneal sepsis was induced in mice expressing either functional TLR4 (TLR4-wild-type [WT]) or mutant TLR4 by intraperitoneal injection of either live Escherichia coli or LPS. Phagocytosis was assessed by measuring the uptake of opsonized red cells. To assess bacterial clearance, we irrigated peritoneal cavities of injected animals with saline and plated it on gram-negative selective media., Results: LPS significantly increased the rate of phagocytosis by peritoneal macrophages from TLR4-WT mice, but not in those from TLR4-mutant mice, suggesting a role for TLR4 in phagocytosis. LPS also increased the rates of phagocytosis in cultured macrophages expressing TLR4, confirming these findings. The yield of gram-negative bacteria obtained from the peritoneal cavities of septic TLR4-WT mice was greater than that from TLR4 mutants, consistent with TLR4-dependent alterations in their septic course., Conclusions: We conclude that TLR4 plays a critical role in the response to intraperitoneal E. coli through effects on phagocytosis by macrophages, suggesting the possibility of using TLR4 as a therapeutic target in diseases of peritoneal sepsis.

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in neonates and is increasing in frequency because of recent advances in neonatal care. NEC develops in a stressed preterm infant in the setting of intestinal barrier disruption, systemic inflammation, and leads to, multisystem organ failure. The intestinal barrier lies at the interface between microbes within the intestinal lumen and the immune system of the host, and has both immunological and mechanical components. These components serve to protect the host from invading pathogens and, at the same time, provide a surface area for nutrient absorption. Factors that lead to impairments in the function of the intestinal barrier may predispose the host to the invasion of gut-derived microbes and to the development of systemic inflammatory disease. This process, termed "bacterial translocation," may be compounded during instances in which the mechanisms that regulate the repair of the intestinal barrier are disrupted. Bacterial translocation is of particular concern to the newborn patient, in which immaturity of the mechanical barrier and incomplete development of the host immune system combine to render the host at particular risk for the development of intestinal inflammation. This review will serve to provide an overview of recent evidence regarding the components of the intestinal barrier, and the mechanisms by which disruptions in barrier function may contribute to the pathogenesis of NEC.

Background: Intussusception is the most common cause of bowel obstruction in infants and children. Although early recurrence is not uncommon, recurrence years later is rare., Methods: A 13-year-old male with a history of recurrent intussusception at ages 2 and 5 presented with recurrent intussusception 8 years later. The diagnosis was made using computed tomography, and the patient underwent a laparoscopic ileocecectomy with an uneventful postoperative course., Results: The specimen was remarkable for findings of multiple enlarged lymph nodes over the serosal surface of the ileum and the terminal ileum with focal edema, prominent lymphoid hyperplasia and large hemorrhagic areas., Conclusion: This case highlights the fact that in a child with a delayed recurrence of intussusception, the presence of a lead point should be suspected, and operative therapy should be strongly considered over hydrostatic reduction. The current management of recurrent intussusception is reviewed and applied to this case.

The systemic inflammatory response syndrome initiated by infection shares many features in common with the trauma-induced systemic response. The toll-like receptors (TLRs) stand at the interface of innate immune activation in the settings of both infection and sterile injury by responding to a variety of microbial and endogenous ligands alike. Recently, a body of literature has evolved describing a key role for TLRs in acute injury using rodent models of hemorrhagic shock, ischemia and reperfusion, tissue trauma and wound repair, and various toxic exposures. This review will detail the observations implicating a TLR family member, TLR4, as a key component of the initial injury response.

Expression of the new 17beta-hydroxysteroid dehydrogenase (HSD), type 10 (17beta-HSD-10), formerly known as endoplasmic reticulum-associated amyloid-binding protein, has been investigated in the testes of various mammals under normal and perturbed conditions. Results show that 17beta-HSD-10 is a major product of both fetal and adult-type Leydig cells. In the former, protein persists until late in postnatal development; and in the short-day hamster model, it does not disappear when Leydig cells involute. During puberty in the rat, immunohistochemical staining for 17beta-HSD-10 in adult-type Leydig cells first becomes evident on d 20, increasing to maximal staining intensity by d 35. In the rat, but not in the mouse or any other species examined, there is also staining in late spermatids. Examination of testes from rats subjected to perinatal treatment with either a GnRH antagonist or low and high doses of diethylstilbestrol revealed that expression of 17beta-HSD-10 follows closely Leydig cell differentiation status, correlating with 3beta-HSD expression in a previous study. In aging (23 months) rat testes, Leydig cell (but not germ cell) immunostaining for 17beta-HSD-10 is markedly reduced. 17beta-HSD-10 seems to preferentially convert 3alpha-androstanediol into dihydrotestosterone, and estradiol to estrone. Thus, perinatal expression of this enzyme in fetal Leydig cells may contribute to protecting these cells from estrogens and encourage androgen formation.

We previously reported the presence of vascular endothelial growth factor (VEGF) in testicular cells, and high concentrations of VEGF have been measured in semen, although its role in male reproduction remains obscure. In the present study we focus on understanding the mechanism of VEGF production by mouse Leydig cells cultured in vitro. Production of VEGF protein in medium by testicular cells was markedly increased by the addition of hCG in a time- and dose-dependent manner. Gonadotropin-stimulated VEGF production was mediated by cAMP-dependent protein kinase A (PKA), as evidenced by the effect of hCG being mimicked by 8Br-cAMP and being abolished in the presence of a PKA-specific inhibitor, H-89. Protein kinase C was not involved, as evidenced by phorbol 12-myristate 13-acetate having no influence on VEGF production by Leydig cells. In addition to hCG, atrial natriuretic peptide was also able to stimulate VEGF production, suggesting that cGMP is able to cross-activate PKA. A specific Src kinase inhibitor, PP2, could completely block the stimulatory effects of both gonadotropin and 8Br-cAMP on VEGF production by Leydig cells, implying an involvement of the Src kinase pathway. Furthermore, addition of U0126, an inhibitor of MEK 1/2, abolished the increase in VEGF production stimulated by both hCG and 8Br-cAMP. A similar inhibitory effect was observed by the addition of SB203580, a p38 mitogen-activated protein kinase inhibitor. Thus, in conclusion, Leydig cells are able to produce VEGF by a process under gonadotropic control, and PKA plays a key role in this process. Downstream of PKA, it appears that both MEK 1/2 and Src kinase-dependent pathways are involved, although further research will be necessary to determine the precise link between PKA and other kinases involved.

Background: The objective of this study was to determine the likelihood of mortality after abdominal aortic aneurysm (AAA) repair in patients with thoracic or thoracoabdominal aortic dissection., Methods: Fourteen patients (11 men, three women) with known thoracic or thoracoabdominal aortic dissections underwent elective AAA repair from 1986 to 2001, including three patients with acute dissections (less than 14 days) and 11 patients with chronic dissections (14 days or longer). All 14 patients had type III aortic dissections. Stent graft exclusion of the aortic dissection was performed in one patient before AAA repair. Preoperative patient characteristics, intraoperative events, perioperative complications, and 30-day and 1-year mortality rates were assessed., Results: Elective AAA repair in the setting of thoracic or thoracoabdominal aortic dissection in this series was associated with no 30-day mortality and a 1-year mortality rate of 7.1%. Furthermore, preoperative patient characteristics, intraoperative events, and perioperative complications did not appear to be associated with late, 1-year, mortality., Conclusion: Elective AAA repair in the setting of acute or chronic aortic dissection is associated with mortality rates similar to those generally attributed to elective AAA repair without accompanying aortic dissection. Nevertheless, the conduct of the operation is usually complex, especially in the setting of an acute aortic dissection.