Endothelial cell-leukemia interactions remodel drug responses, uncovering T-ALL vulnerabilities.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and often incurable disease. To uncover therapeutic vulnerabilities, we first developed T-ALL patient-derived tumor xenografts (PDXs) and exposed PDX cells to a library of 433 clinical-stage compounds in vitro. We identified 39 broadly active drugs with antileukemia activity. Because endothelial cells (ECs) can alter drug responses in T-ALL, we developed an EC/T-ALL coculture system. We found that ECs provide protumorigenic signals and mitigate drug responses in T-ALL PDXs. Whereas ECs broadly rescued several compounds in most models, for some drugs the rescue was restricted to individual PDXs, suggesting unique crosstalk interactions and/or intrinsic tumor features. Mechanistically, cocultured T-ALL cells and ECs underwent bidirectional transcriptomic changes at the single-cell level, highlighting distinct "education signatures." These changes were linked to bidirectional regulation of multiple pathways in T-ALL cells as well as in ECs. Remarkably, in vitro EC-educated T-ALL cells transcriptionally mirrored ex vivo splenic T-ALL at single-cell resolution. Last, 5 effective drugs from the 2 drug screenings were tested in vivo and shown to effectively delay tumor growth and dissemination thus prolonging overall survival. In sum, we developed a T-ALL/EC platform that elucidated leukemia-microenvironment interactions and identified effective compounds and therapeutic vulnerabilities.

Gestalt clinical severity score (GCSS) as a predictor of patient severity of illness or injury.

OBJECTIVE: To determine if clinical judgement is accurate to predict the severity of injury or illness, and can be used at patient arrival when other formal scoring systems are not yet available. DESIGN: A multicenter pilot study using a prospective observational convenience sample of patients arriving by EMS to the emergency department (ED) or Trauma Center. SETTING: Two urban, Level 1 trauma centers at academic tertiary care hospitals. PATIENTS: Medical and trauma patients age 18 and older transported by EMS (N = 216). Exclusion criteria (prior to arrival): intubation, assisted ventilation (BVM or NPPV), CPR in progress, prisoners, or previously present motor or speech deficits. MEASUREMENTS: Completion of a novel 15-point scale of Verbal, Motor, and Facial Expression within 1-2 min of arrival by a clinician outside of the treatment team. Primary endpoint was the immediate disposition from the ED or Trauma Center: Home, Brief Observation (<24 h), Admission to Floor, ICU (OR and IR as surrogates since these patients ultimately go to the ICU), or Morgue. RESULTS: Univariate analysis revealed a strong, positive monotonic correlation between GCSS and disposition (Rho = 0.693, p < .0001). Multivariable logistic regression revealed the "best" model included GCSS and age (group 18-44 years old versus all the other age groups) (p < .0001). There was a 156% increase in the odds of being discharged home (versus being admitted) for a one-unit increase in GCSS (OR = 2.56, 95% CI 1.94, 3.37). CONCLUSIONS: Physicians can make accurate predictions of severity of injury and illness using a gestalt method and the scoring system we have developed as patient disposition correlates well with GCSS score. GCSS is most accurate with the 18-44 age group.

A catalog of Xenopus tropicalis transcription factors and their regional expression in the early gastrula stage embryo.

Gene regulatory networks (GRNs) involve highly combinatorial interactions between transcription factors and short sequence motifs in cis-regulatory modules of target genes to control cellular phenotypes. The GRNs specifying most cell types are largely unknown and are the subject of wide interest. A catalog of transcription factors is a valuable tool toward obtaining a deeper understanding of the role of these critical effectors in any biological setting. Here we present a comprehensive catalog of the transcription factors for the diploid frog Xenopus tropicalis. We identify 1235 genes encoding DNA-binding transcription factors, comparable to the numbers found in typical mammalian species. In detail, the repertoire of X. tropicalis transcription factor genes is nearly identical to human and mouse, with the exception of zinc finger family members, and a small number of species/lineage-specific gene duplications and losses relative to the mammalian repertoires. We applied this resource to the identification of transcription factors differentially expressed in the early gastrula stage embryo. We find transcription factor enrichment in Spemann's organizer, the ventral mesoderm, ectoderm and endoderm, and report 218 TFs that show regionalized expression patterns at this stage. Many of these have not been previously reported as expressed in the early embryo, suggesting thus far unappreciated roles for many transcription factors in the GRNs regulating early development. We expect our transcription factor catalog will facilitate myriad studies using Xenopus as a model system to understand basic biology and human disease.

Genome-wide view of TGFß/Foxh1 regulation of the early mesendoderm program.

Nodal/TGFß signaling regulates diverse biological responses. By combining RNA-seq on Foxh1 and Nodal signaling loss-of-function embryos with ChIP-seq of Foxh1 and Smad2/3, we report a comprehensive genome-wide interaction between Foxh1 and Smad2/3 in mediating Nodal signaling during vertebrate mesendoderm development. This study significantly increases the total number of Nodal target genes regulated by Foxh1 and Smad2/3, and reinforces the notion that Foxh1-Smad2/3-mediated Nodal signaling directly coordinates the expression of a cohort of genes involved in the control of gene transcription, signaling pathway modulation and tissue morphogenesis during gastrulation. We also show that Foxh1 may function independently of Nodal signaling, in addition to its role as a transcription factor mediating Nodal signaling via Smad2/3. Finally, we propose an evolutionarily conserved interaction between Foxh1 and PouV, a mechanism observed in Pou5f1-mediated regulation of pluripotency in human embryonic stem and epiblast cells.

Acoustic sensor versus electrocardiographically derived respiratory rate in unstable trauma patients.

Respiratory rate (RR) is important in many patient care settings; however, direct observation of RR is cumbersome and often inaccurate, and electrocardiogram-derived RR (RRECG) is unreliable. We asked how data derived from the first 15 min of RR recording after trauma center admission using a novel acoustic sensor (RRa) would compare to RRECG and to end-tidal carbon dioxide-based RR ([Formula: see text]) from intubated patients, the "gold standard" in predicting life-saving interventions in unstable trauma patients. In a convenience sample subset of trauma patients admitted to our Level 1 trauma center, enrolled in the ONPOINT study, and monitored with RRECG, some of whom also had [Formula: see text] data, we collected RRa using an adhesive sensor with an integrated acoustic transducer (Masimo RRa™). Using Bland-Altman analysis of area under the receiver operating characteristic (AUROC) curves, we compared the first 15 min of continuous RRa and RRECG to [Formula: see text] and assessed the performance of these three parameters compared to the Revised Trauma Score (RTS) in predicting blood transfusion 3, 6, and 12 h after admission. Of the 1200 patients enrolled in ONPOINT from December 2011 to May 2013, 1191 had RRECG data recorded in the first 15 min, 358 had acoustic monitoring, and 14 of the latter also had [Formula: see text]. The three groups did not differ demographically or in mechanism of injury. RRa showed less bias (0.8 vs. 6.9) and better agreement than RRECG when compared to [Formula: see text]. At [Formula: see text] 10-29 breaths per minute, RRa was more likely to be the same as [Formula: see text] and assign the same RTS. In predicting transfusion, features derived from RRa and RRECG gave AUROCs 0.59-0.66 but with true positive rate 0.70-0.89. RRa monitoring is a non-invasive option to glean valid RR data to assist clinical decision making and could contribute to prediction models in non-intubated unstable trauma patients.

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

MDCT diagnosis of post-traumatic hepatic arterio-portal fistulas.

The purpose of this study is to evaluate the performance of multidetector computed tomography (MDCT) in diagnosing arterioportal fistulas (APF) in high-grade liver injury. A retrospective analysis of catheter-based hepatic angiograms performed for major penetrating and blunt liver injuries identified 11 patients with APFs. Using the trauma registry, two additional demographically matched groups with and without liver injury were formed. A randomized qualitative consensus review of 33 MDCTs was performed by three trauma radiologists for the following MDCT findings of APF: transient hepatic parenchymal attenuation differences (THPAD), early increased attenuation of a peripheral or central portal vein compared with the main portal vein, and the "double-barrel" or "rail tract" signs. THPAD was the most sensitive finding and also had a high specificity for diagnosing APF. Both the early increased attenuation of a peripheral or central portal vein compared with the main portal vein and the double-barrel or rail tract signs had a100% specificity and a sensitivity of 64% and 36%, respectively. Measurement of differences in attenuation values between the APF and the contralateral central portal vein was most sensitive and specific in diagnosing APF. Traumatic APF of the liver can be optimally diagnosed with arterial phase imaging of solid organ using MDCT.

Full of sound and fury, signifying nothing: burden of transient noncritical monitor alarms in a trauma resuscitation unit.

We examined the types of patient monitor alarms encountered in the trauma resuscitation unit of a major level 1 trauma center. Over a 1-year period, 316688 alarms were recorded for 6701 trauma patients (47 alarms/patient). Alarms were more frequent among patients with a Glasgow Coma Scale of 8 or less. Only 2.4% of all alarms were classified as "patient crisis," with the rest in the presumably less critical categories "patient advisory," "patient warning," and "system warning." Nearly half of alarms were ≤5 seconds in duration. In this patient population, a 2-second delay would reduce alarms by 25%, and a delay of 5 seconds would reduce all alarms by 49%.

Contributions of Surgical Critical Care Program Directors Society to the training of surgeons.

BACKGROUND: In 1986, Surgical Critical Care (SCC) was formally recognized as a specialty by the American Board of Surgery (ABS), however it took another two decades to develop a formal national training structure in SCC. In 2003, the program directors of SCC fellowships began to meet and the Surgical Critical Care Program Directors Society (SCCPDS) was officially formed in 2004, with recognition of the SCCPDS as a non-profit organization in 2008. Over the next several years, and in conjunction with other interested groups, such as the American Association for the Surgery of Trauma (AAST) and the Society of Critical Care Medicine (SCCM), SCCPDS created a formal curriculum, developed a unified system for the fellowship application process, and increased recruitment and match such that now approximately 1 in 6 general surgery graduates are pursuing training in SCC. In discussion with past and present leadership of SCCPDS, there are several ongoing initiatives to further improve the educational opportunities of the fellows and increase inclusion of other organizations and other specialties interested in SCC. The purpose of this article is to discuss the role of SCCPDS in the development and evolution of SCC and Acute Care Surgery (ACS) training. LEVEL OF EVIDENCE: Expert Opinion; Level V.

Survey of surgical critical care applicant and program director views on virtual interviews for fellowship training: a Surgical Critical Care Program Directors Society sponsored study.

Background: The COVID-19 pandemic forced postgraduate interview processes to move to a virtual platform. There are no studies on the opinions of faculty and applicants regarding this format. The aim of this study was to assess the opinions of surgical critical care (SCC) applicants and program directors regarding the virtual versus in-person interview process. Methods: An anonymous survey of the SCC Program Director's Society members and applicants to the 2019 (in-person) and 2020 (virtual) interview cycles was done. Demographic data and Likert scale based responses were collected using Research Electronic Data Capture. Results: Fellowship and program director responses rates were 25% (137/550) and 58% (83/143), respectively. Applicants in the 2020 application cycle attended more interviews. The majority of applicants (57%) and program faculty (67%) strongly liked/liked the virtual interview format but felt an in-person format allows better assessment of the curriculum and culture of the program. Both groups felt that an in-person format allows applicants and faculty to establish rapport better. Only 9% and 16% of SCC program directors wanted a purely virtual or purely in-person interview process, respectively. Applicants were nearly evenly split between preferring a purely in-person versus virtual interviews in the future. Discussion: The virtual interview format allows applicants and program directors to screen a larger number of programs and applications. However, the virtual format is less useful than an in-person interview format for describing unique aspects of a training program and for allowing faculty and applicants to establish rapport. Future strategies using both formats may be optimal, but such an approach requires further study. Level of evidence: Epidemiologic level IV.

A disturbing trend: An analysis of the decline in surgical critical care fellowship training of Black and Hispanic surgeons.

BACKGROUND: Underrepresented minorities in medicine (URiMs) are disproportionally represented in surgery training programs. Rates of URiMs applying to and completing General Surgery residency remain low. We hypothesized that the patterns of URiMs disparities would persist into surgical critical care (SCC) fellowship applicants, matriculants, and graduates. METHODS: We performed a retrospective analysis of SCC applicants, matriculants, and graduates from 2005 to 2020 using the graduate medical education resident survey and analyzed applicant characteristics using the Surgical Critical Care and Acute Care Surgery Fellowship Application Service from 2018 to 2020. The data were stratified by race/ethnicity and sex. Indicator variables were created for Asian, Hispanic, White, and Black trainees. Yearly proportions for each race/ethnicity and sex categories completing or enrolling in a program were calculated and plotted over time with Loess smoothing lines and overlying 95% confidence bands. The yearly rate and statistical significance of change over time were tested with linear regression models with race/ethnicity and sex proportion as the dependent variables and year as the explanatory variable. RESULTS: From 2005 to 2020, there were a total of 2,481 graduates. Black men accounted for 4.7% of male graduates with a significant decline of 0.3% per year for the study period of those completing the fellowship (p = 0.02). Black women comprised 6.4% of female graduates and had a 0.6% decline each year (p < 0.01). A similar trend was seen with Hispanic men, who comprised 3.2% of male graduates and had a 0.3% annual decline (p = 0.02). White men had a significant increase in both matriculation to and graduation from SCC fellowships during the same interval. Similarly, Black and Hispanic applicants declined from 2019 to 2020, while the percentage of White applicants increased. CONCLUSION: Disparities in URiMs representation remain omnipresent in surgery and extend from residency training to SCC fellowship. Efforts to enhance the recruitment and retention of URiMs in SCC training are warranted. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; level IV.

Vaccination after spleen embolization: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Angioembolization is an important adjunct in the non-operative management of adult trauma patients with splenic injury. Multiple studies have shown that angioembolization may increase the non-operative splenic salvage rate for patients with high-grade splenic injuries. We performed a systematic review and developed evidence-based recommendations regarding the need for post-splenectomy vaccinations after splenic embolization in trauma patients. METHODS: A systematic review and meta-analysis of currently available evidence were performed utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Nine studies were identified and analyzed. A total of 240 embolization patients were compared to 443 control patients who neither underwent splenectomy nor were embolized. There was no statistical difference between the splenic immune function of embolized and control patients. In addition, a total of 3974 splenectomy patients was compared with 686 embolization patients. Embolization patients had fewer infectious complications and a greater degree of preserved splenic immune function. CONCLUSION: In adult trauma patients who have undergone splenic angioembolization, we conditionally recommend against routine post-splenectomy vaccinations. STUDY TYPE: systematic review/meta-analysis Level of evidence: level III.

Impact of trauma centre capacity and volume on the mortality risk of incoming new admissions.

INTRODUCTION: Trauma centre capacity and surge volume may affect decisions on where to transport a critically injured patient and whether to bypass the closest facility. Our hypothesis was that overcrowding and high patient acuity would contribute to increase the mortality risk for incoming admissions. METHODS: For a 6-year period, we merged and cross-correlated our institutional trauma registry with a database on Trauma Resuscitation Unit (TRU) patient admissions, movement and discharges, with average capacity of 12 trauma bays. The outcomes of overall hospital and 24 hours mortality for new trauma admissions (NEW) were assessed by multivariate logistic regression. RESULTS: There were 42 003 (mean=7000/year) admissions having complete data sets, with 36 354 (87%) patients who were primary trauma admissions, age ≥18 and survival ≥15 min. In the logistic regression model for the entire cohort, NEW admission hospital mortality was only associated with NEW admission age and prehospital Glasgow Coma Scale (GCS) and Shock Index (SI) (all p<0.05). When TRU occupancy reached ≥16 patients, the factors associated with increased NEW admission hospital mortality were existing patients (TRU >1 hour) with SI ≥0.9, recent admissions (TRU ≤1 hour) with age ≥65, NEW admission age and prehospital GCS and SI (all p<0.05). CONCLUSION: The mortality of incoming patients is not impacted by routine trauma centre overcapacity. In conditions of severe overcrowding, the number of admitted patients with shock physiology and a recent surge of elderly/debilitated patients may influence the mortality risk of a new trauma admission.

Training dedicated emergency physicians in surgical critical care: knowledge acquisition and workforce collaboration for the care of critically ill trauma/surgical patients.

BACKGROUND: The Leapfrog Group initiative has led to an increasing public demand for dedicated intensivists providing critical care services. The Acute Care Surgery training initiative promotes an expansion of trauma/surgical care and operative domain, redirecting some of our focus from critical care. Will we be able to train and enforce enough intensivists to care for critically ill surgical patients? METHODS: We have been training emergency physicians (EPs) alongside surgeons in our country's largest Trauma/Surgical Critical Care Fellowship Program annually for more than a decade. We reviewed our Society of Critical Care Medicine Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP, critical care in-training examination) scores from 2006 to 2009 (4 years). The MCCKAP, administered during the ninth month of a Critical Care Fellowship, is the only known standardized objective examination available in this country to compare critical care knowledge acquisition across different specialties. Subsequent workforce outcome for these Emergency Medicine Critical Care Fellowship graduates was analyzed. RESULTS: Over the 4-year period, we trained 42 Fellows in our Program who qualified for this study (30 surgeons and 12 EPs). Surgeons and EP performance scores on the MCCKAP examination were not different. The mean National Board Equivalent score was 419 ± 61 (mean ± standard deviation) for surgeons and 489 ± 87 for EPs. The highest score was achieved by an EP. The lowest score was not achieved by an EP. Ten of 12 (83%) EP Critical Care Fellowship graduates are practicing inpatient critical care in intensive care units with attending physician level responsibilities. CONCLUSIONS: EPs training in a Surgical Critical Care Fellowship can acquire critical care knowledge equivalent to that of surgeons. EPs trained in a Surgical Critical Care paradigm can potentially expand the intensive care unit workforce for Surgical Critical Care patients.

Seven-Year Follow-Up of an Online Critical Care Curriculum.

Background: In July of 2013, the University of Maryland launched MarylandCCProject.com. This free-access educational website delivers asynchronous high-quality multidisciplinary critical care education targeted at critical care trainees. The lectures, presented in real time on-site, are recorded and available on the website or as a podcast on iTunes or Android. Thus, the curriculum can be easily accessed around the world.Objective: We sought to identify the impact this website has on current and former University of Maryland critical care trainees.Methods: A 32-question survey was generated using a standard survey generation tool. The survey was e-mailed in the fall of 2019 to the University of Maryland Multi-Departmental Critical Care current and graduated trainees from the prior 7 years. Survey data were collected through December 2019. The questions focused on user demographics, overall experience with the website, scope of website use, and clinical application of the content. Anonymous responses were electronically gathered.Results: A total of 186 current trainees and graduates were surveyed, with a 39% (n = 72) response rate. Of responders, 76% (55) use the website for ongoing medical education. The majority use the website at least monthly. Most users (63%, n = 35) access the lectures directly through the website. All 55 current users agree that the website has improved their medical knowledge and is a useful education resource. Platform use has increased and includes users from around the world.Conclusion: Based on our current data, the MarylandCCProject remains a valuable and highly used educational resource, impacting patient care both during and after critical care fellowship training.

Practice management guidelines for selective nonoperative management of penetrating abdominal trauma.

BACKGROUND: : Although there is no debate that patients with peritonitis or hemodynamic instability should undergo urgent laparotomy after penetrating injury to the abdomen, it is also clear that certain stable patients without peritonitis may be managed without operation. The practice of deciding which patients may not need surgery after penetrating abdominal wounds has been termed selective management. This practice has been readily accepted during the past few decades with regard to abdominal stab wounds; however, controversy persists regarding gunshot wounds. Because of this, the Eastern Association for the Surgery of Trauma Practice Management Guidelines Committee set out to develop guidelines to analyze which patients may be managed safely without laparotomy after penetrating abdominal trauma. A secondary goal of this committee was to find which diagnostic adjuncts are useful in the determination of the need for surgical exploration. METHODS: : A search of the National Library of Medicine and the National Institutes of Health MEDLINE database was performed using PubMed (www.pubmed.gov). RESULTS: : The search retrieved English language articles concerning selective management of penetrating abdominal trauma and related topics from the years 1960 to 2007. These articles were then used to construct this set of practice management guidelines. CONCLUSIONS: : Although the rate of nontherapeutic laparotomies after penetrating wounds to the abdomen should be minimized, this should never be at the expense of a delay in the diagnosis and treatment of injury. With this in mind, a routine laparotomy is not indicated in hemodynamically stable patients with abdominal stab wounds without signs of peritonitis or diffuse abdominal tenderness. Likewise, it is also not routinely indicated in stable patients with abdominal gunshot wounds if the wounds are tangential and there are no peritoneal signs. Abdominopelvic computed tomography should be considered in patients selected for initial nonoperative management to facilitate initial management decisions. The majority of patients with penetrating abdominal trauma managed nonoperatively may be discharged after 24 hours of observation in the presence of a reliable abdominal examination and minimal to no abdominal tenderness. Diagnostic laparoscopy may be considered as a tool to evaluate diaphragmatic lacerations and peritoneal penetration in an effort to avoid unnecessary laparotomy.

Practice management guidelines for the diagnosis and management of injury in the pregnant patient: the EAST Practice Management Guidelines Work Group.

Trauma during pregnancy has presented very unique challenges over the centuries. From the first report of Ambrose Pare of a gunshot wound to the uterus in the 1600s to the present, there have existed controversies and inconsistencies in diagnosis, management, prognostics, and outcome. Anxiety is heightened by the addition of another, smaller patient. Trauma affects 7% of all pregnancies and requires admission in 4 of 1000 pregnancies. The incidence increases with advancing gestational age. Just over half of trauma during pregnancy occurs in the third trimester. Motor vehicle crashes comprise 50% of these traumas, and falls and assaults account for 22% each. These data were considered to be underestimates because many injured pregnant patients are not seen at trauma centers. Trauma during pregnancy is the leading cause of nonobstetric death and has an overall 6% to 7% maternal mortality. Fetal mortality has been quoted as high as 61% in major trauma and 80% if maternal shock is present. The anatomy and physiology of pregnancy make diagnosis and treatment difficult.

Mapping the increasing interest in acute care surgery-Who, why and which fellowship?

BACKGROUND: Interest in acute care surgery (ACS) has increased over the past 10 years as demonstrated by the linear increase in fellowship applicants to the different fellowships leading to ACS careers. It is unclear why interest has increased, whether various fellowship pathways attract different applicants or whether fellowship choice correlates with practice patterns after graduation. METHODS: An online survey was distributed to individuals previously registered with the Surgical critical care and Acute care surgery Fellowship Application Service. Fellowship program directors were also asked to forward the survey to current and former fellows to increase the response rate. Data collected included demographics, clinical interests and motivations, publications, and postfellowship practice patterns. Fisher's exact and Pearson's χ were used to determine significance. RESULTS: Trauma surgery was the primary clinical interest for all fellowship types (n = 273). Fellowship type had no impact on academic productivity or practice patterns. Most fellows would repeat their own fellowship. The 2-year American Association for the Surgery of Trauma-approved fellowship was nearly uniformly reported as the preferred choice among those who would perform a different fellowship. Career motivations were similar across fellowships and over time though recent trainees were more likely to consider predictability of schedule a significant factor in career choice. Respondents reported graduated progression to full responsibility, further exposure to trauma care and additional operative technical training as benefits of a second fellowship year. CONCLUSION: American Association for the Surgery of Trauma-approved 2-year fellows appear to be the most satisfied with their fellowship choice. No differences were noted in academic productivity or practice between fellowships. Future research should focus on variability in trauma training and operative experience during residency and in practice to better inform how a second fellowship year would improve training for ACS careers. LEVEL OF EVIDENCE: Descriptive, mixed methods, Level IV.

Clinical practice guideline: red blood cell transfusion in adult trauma and critical care.

OBJECTIVE: To develop a clinical practice guideline for red blood cell transfusion in adult trauma and critical care. DESIGN: Meetings, teleconferences and electronic-based communication to achieve grading of the published evidence, discussion and consensus among the entire committee members. METHODS: This practice management guideline was developed by a joint taskforce of EAST (Eastern Association for Surgery of Trauma) and the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM). We performed a comprehensive literature review of the topic and graded the evidence using scientific assessment methods employed by the Canadian and U.S. Preventive Task Force (Grading of Evidence, Class I, II, III; Grading of Recommendations, Level I, II, III). A list of guideline recommendations was compiled by the members of the guidelines committees for the two societies. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by the EAST Board of Directors, the Board of Regents of the ACCM and the Council of SCCM. RESULTS: Key recommendations are listed by category, including (A) Indications for RBC transfusion in the general critically ill patient; (B) RBC transfusion in sepsis; (C) RBC transfusion in patients at risk for or with acute lung injury and acute respiratory distress syndrome; (D) RBC transfusion in patients with neurologic injury and diseases; (E) RBC transfusion risks; (F) Alternatives to RBC transfusion; and (G) Strategies to reduce RBC transfusion. CONCLUSIONS: Evidence-based recommendations regarding the use of RBC transfusion in adult trauma and critical care will provide important information to critical care practitioners.

Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel with plasma adrenocorticotropin during sepsis in the rat.

Loss of appetite occurs in the cecal ligation and puncture (CLP) model of sepsis in conjunction with the activation of central neural stress pathways. Neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus is upregulated by several stressors and is stimulatory to feeding. To examine the response of NPY messenger RNA in the arcuate nucleus to sepsis, we used biotinylated RNA probes and a quantitative non-isotopic in situ hybridization approach in cryo-preserved sections from rats made septic by CLP. The mRNA in arcuate neurons was upregulated from the first day after CLP. By the afternoon of the third day through the morning of the fourth day, the average grey level of NPY mRNA clusters was 30% greater after CLP than after sham surgery (P<0.05), and the integrated optical density based on both the grey level and the amount of area with detectable mRNA was 60% greater after CLP than after sham surgery (P<0.03). Both the average grey level and area with detectable staining were positively correlated to plasma ACTH (r=0.953 and 0.917, respectively, n=10 and P<0.01 in each case). Thus sepsis increases the expression of the mRNA for NPY in the arcuate nucleus in proportion to the magnitude of the stress response. However, the suppression of feeding behavior in the CLP model suggests that sepsis activates additional mechanisms that negate the orexigenic contribution of the neuronal increase in NPY mRNA.