Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. Objective: To determine whether adding sigh breaths improves clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. Main Outcomes and Measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). Conclusions and Relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02582957.

Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality.

BACKGROUND: Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation. STUDY DESIGN: A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors. RESULTS: A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with >70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03). CONCLUSIONS: Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury.

Value in acute care surgery, part 2: Defining and measuring quality outcomes.

ABSTRACT: The prior article in this series delved into measuring cost in acute care surgery, and this subsequent work explains in detail how quality is measured. Specifically, objective quality is based on outcome measures, both from administrative and clinical registry databases from a multitude of sources. Risk stratification is key in comparing similar populations across diseases and procedures. Importantly, a move toward focusing on subjective outcomes like patient-reported outcomes measures and financial well-being are vital to evolving surgical quality measures for the 21st century.

Data resources for evaluating the economic and financial consequences of surgical care in the United States.

ABSTRACT: Evaluating the relationship between health care costs and quality is paramount in the current health care economic climate, as an understanding of value is needed to drive policy decisions. While many policy analyses are focused on the larger health care system, there is a pressing need for surgically focused economic analyses. Surgical care is costly, and innovative technology is constantly introduced into the operating room, and surgical care impacts patients' short- and long-term physical and economic well-being. Unfortunately, significant knowledge gaps exist regarding the relationship between cost, value, and economic impact of surgical interventions. Despite the plethora of health care data available in the forms of claims databases, discharge databases, and national surveys, no single source of data contains all the information needed for every policy-relevant analysis of surgical care. For this reason, it is important to understand which data are available and what can be accomplished with each of the data sets. In this article, we provide an overview of databases commonly used in surgical health services research. We focus our review on the following five categories of data: governmental claims databases, commercial claims databases, hospital-based clinical databases, state and national discharge databases, and national surveys. For each, we present a summary of the database sampling frame, clinically relevant variables, variables relevant to economic analyses, strengths, weaknesses, and examples of surgically relevant analyses. This review is intended to improve understanding of the current landscape of data available, as well as stimulate novel analyses among surgical populations. Ongoing debates over national health policy reforms may shape the delivery of surgical care for decades to come. Appropriate use of available data resources can improve our understanding of the economic impact of surgical care on our health care system and our patients. LEVEL OF EVIDENCE: Regular Review, Level V.

Value in acute care surgery, Part 1: Methods of quantifying cost.

BACKGROUND: With health care expenditures continuing to increase rapidly, the need to understand and provide value has become more important than ever. In order to determine the value of care, the ability to accurately measure cost is essential. The acute care surgeon leader is an integral part of driving improvement by engaging in value increasing discussions. Different approaches to quantifying cost exist depending on the purpose of the analysis and available resources. Cost analysis methods range from detailed microcosting and time-driven activity-based costing to less complex gross and expenditure-based approaches. An overview of these methods and a practical approach to costing based on the needs of the acute care surgeon leader is presented.

Multidisciplinary Management of Severe Traumatic Hepatic Injury Involving Interventional Radiology Embolization, Trauma Laparotomy, and Liver Transplantation.

This report describes liver transplantation as a successful strategy in the management of a young man who presented to a local emergency room following catastrophic traumatic hepatic vascular injuries. Expeditious multidisciplinary management, including interventional radiology, trauma surgery, and ultimately transplant surgery, provided the patient with definitive therapy following his injuries and early return to normal activity. Our experience highlights the importance of prompt referral of select hepatic trauma patients for liver transplant evaluation as part of their complex trauma management.

Results and lessons from a hospital-wide initiative incentivised by delivery system reform to improve infection prevention and sepsis care.

BACKGROUND: An academic safety-net hospital leveraged the federally funded state Delivery System Reform Incentive Payment programme to implement a hospital-wide initiative to reduce healthcare-associated infections (HAIs) and improve sepsis care. METHODS: The study period was from 2013 to 2017. The setting is a 770-bed urban hospital with six intensive care units and a large emergency department. Key interventions implemented were (1) awareness campaign and clinician engagement, (2) implementation of HAI and sepsis bundles, (3) education of clinical personnel using standardised curriculum on bundles, (4) training of key managers, leaders and personnel in quality improvement methods, and (5) electronic medical record-based clinical decision support. Throughout the 5-year period, staff received frequent, clear, visible and consistent messages from leadership regarding the importance of their participation in this initiative, performing hand hygiene and preventing potential regulatory failures. Several process measures including bundle compliance, hand hygiene and culture of safety were monitored. The primary outcomes were rates of central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI) and sepsis mortality. RESULTS: From 2013 to 2017, the hospital-wide rates of HAI reduced: CLABSI from 1.6 to 0.8 per 1000 catheter-days (Poisson regression estimate: -0.19; 95% CI -0.29 to -0.09; p=0.0002), CAUTI from 4.7 to 1.3 per 1000 catheter-days (-0.34; -0.43 to -0.26; p<0.0001) and SSI after 18 types of procedures from 3.4% to 1.3% (-0.29; -0.34 to -0.24; p<0.0001). Mortality of patients presenting to emergency department with sepsis reduced from 9.4% to 2.9% (-0.42; -0.49 to -0.36; p<0.0001). Adherence to bundles of care and hand hygiene and the hospital culture of patient safety improved. Results were sustained through 2019. CONCLUSION: A hospital-wide initiative incentivised by the Delivery System Reform Incentive Payment programme succeeded in reducing HAI and sepsis mortality over 5 years in a sustainable manner.

Fast track pathway provides safe, value based care on busy acute care surgery service.

BACKGROUND: Fast track (FT) pathways have been adopted across a multitude of elective surgeries but have been slow to be adopted into the acute care surgery realm. We hypothesized that an FT pathway for acute cholecystitis patients would decrease patient length of stay and resource utilization. METHODS: All patients at two hospitals, one with an FT pathway and one with a traditional pathway, who underwent an urgent laparoscopic cholecystectomy for acute cholecystitis between May 1, 2019, and October 31, 2019, were queried using CPT codes. Exclusion criteria were conversion to open or partial cholecystectomy. Retrospective chart review was used to gather demographics, operative, hospital course, and outcomes. Time to operating room, hospital length of stay, and resource utilization were the primary outcomes. RESULTS: There was a total of 479 urgent laparoscopic cholecystectomies performed, 430 (89.8%) were performed under the FT pathway. The median (interquartile range [IQR]) time to the operating room was not different: 14.1 hours (IQR, 8.3-29.0 hours) for FT and 18.5 hours (IQR, 11.9-25.9 hours) for traditional (p = 0.316). However, the median length of stay was shorter by 15.9 hours in the FT cohort (22.6 hours; IQR, 14.2-40.4 hours vs. 38.5 hours; IQR, 28.3-56.3 hours; p < 0.001). Under the FT pathway, 33.0% of patients were admitted to the hospital and 75.6% were discharged from the postanesthesia care unit, compared with 91.8% and 12.2% on the traditional pathway (both p < 0.001). There were 59.6% of the FT patients that received a phone call follow up, as opposed to 100% of the traditional patients having clinic follow up (p < 0.001). The emergency department bounce back rate, readmission rates, and complication rates were similar (p > 0.2 for all). On multivariate analysis, having a FT pathway was an independent predictor of discharge within 24 hours of surgical consultation (odds ratio, 7.65; 95% confidence interval< 2.90-20.15; p < 0.001). CONCLUSION: Use of a FT program for patients with acute cholecystitis has a significant positive impact on resource utilization without compromise of clinical outcomes. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Comparison of Appendectomy for Perforated Appendicitis With and Without Abscess: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: Outcomes of appendectomy stratified by type of complicated appendicitis (CA) features are poorly researched, and the evidence to guide operative versus nonoperative management for CA is lacking. This study aimed to determine laparoscopic-to-open conversion risk, postoperative abscess risk, unplanned readmission risk, and length of hospital stay (LOS) associated with appendectomy in patients with perforated appendicitis without abscess (PA) and perforated appendicitis with abscess (PAWA) compared with a control cohort of nonperforated appendicitis (NPA). METHODS: The 2016-2017 National Surgical Quality Improvement Program Appendectomy-targeted database identified 12,537 (76.1%) patients with NPA, 2142 (13.0%) patients with PA, and 1799 (10.9%) patients with PAWA. Chi-squared analysis and analysis of variance were used to compare categorical and continuous variables. Binary logistic and linear regression models were used to compare risk-adjusted outcomes. RESULTS: Compared with NPA, PA and PAWA had higher rates of conversion (0.8% versus 4.9% and 6.5%, respectively; P < 0.001), postoperative abscess requiring intervention (0.6% versus 4.8% and 7.0%, respectively; P < 0.001), readmission (2.8% versus 7.7% and 7.6%, respectively; P < 0.001), and longer median LOS (1 day versus 2 days and 2 days, respectively; P < 0.001). PA and PAWA were associated with increased odds of postoperative abscess (odds ratio [OR]: 7.18, 95% confidence interval [CI]: 5.2-9.8 and OR: 9.94, 95% CI: 7.3-13.5, respectively), readmission (OR: 2.70, 95% CI: 2.1-3.3 and OR: 2.66, 95% CI: 2.2-3.3, respectively), and conversion (OR: 5.51, 95% CI: 4.0-7.5 and OR: 7.43, 95% CI: 5.5-10.1, respectively). PA was associated with an increased LOS of 1.7 days and PAWA with 1.9 days of LOS (95% CI: 1.5-1.8 and 1.7-2.1, respectively). CONCLUSIONS: Individual features of CA were independently associated with outcomes. Further research is needed to determine if surgical management is superior to nonoperative management for CA.

Benchmarking the value of care: Variability in hospital costs for common operations and its association with procedure volume.

BACKGROUND: Efforts to improve health care value (quality/cost) have become a priority in the United States. Although many seek to increase quality by reducing variability in adverse outcomes, less is known about variability in costs. In conjunction with the American Association for the Surgery of Trauma Healthcare Economics Committee, the objective of this study was to examine the extent of variability in total hospital costs for two common procedures: laparoscopic appendectomy (LA) and laparoscopic cholecystectomy (LC). METHODS: Nationally weighted data for adults 18 years and older was obtained for patients undergoing each operation in the 2014 and 2016 National Inpatient Sample. Data were aggregated at the hospital-level to attain hospital-specific median index hospital costs in 2019 US dollars and corresponding annual procedure volumes. Cost variation was assessed using caterpillar plots and risk-standardized observed/expected cost ratios. Correlation analysis, variance decomposition, and regression analysis explored costs' association with volume. RESULTS: In 2016, 1,563 hospitals representing 86,170 LA and 2,276 hospitals representing 230,120 LC met the inclusion criteria. In 2014, the numbers were similar (1,602 and 2,259 hospitals). Compared with a mean of US $10,202, LA median costs ranged from US $2,850 to US $33,381. Laparoscopic cholecystectomy median costs ranged from US $4,406 to US $40,585 with a mean of US $12,567. Differences in cost strongly associated with procedure volume. Volume accounted for 9.9% (LA) and 12.4% (LC) of variation between hospitals, after controlling for the influence of other hospital (8.2% and 5.0%) and patient (6.3% and 3.7%) characteristics and in-hospital complications (0.8% and 0.4%). Counterfactual modeling suggests that were all hospitals to have performed at or below their expected median cost, one would see a national cost savings of greater than US $301.9 million per year (95% confidence interval, US $280.6-325.5 million). CONCLUSION: Marked variability of median hospital costs for common operations exists. Differences remained consistent across changing coding structures and database years and were strongly associated with volume. Taken together, the findings suggest room for improvement in emergency general surgery and a need to address large discrepancies in an often-overlooked aspect of value. LEVEL OF EVIDENCE: Epidemiological, level III.

Clinical Diagnosis of Infection in Surgical Intensive Care Unit: You're Not as Good as You Think!

Background: Because of the everincreasing costs and the complexity of institutional medical reimbursement policies, the necessity for extensive laboratory work-up of potentially infected patients has come into question. We hypothesized that intensivists are able to differentiate between infected and non-infected patients clinically, without the need to pan-culture, and are able to identify the location of the infection clinically in order to administer timely and appropriate treatment. Methods: Data collected prospectively on critically ill patients suspected of having an infection in the surgical intensive care unit (SICU) was obtained over a six-month period in a single tertiary academic medical center. Objective evidence of infection derived from laboratory or imaging data was compared with the subjective answers of the three most senior physicians' clinical diagnoses. Results: Thirty-nine critically ill surgical patients received 52 work-ups for suspected infections on the basis of signs and symptoms (e.g., fever, altered mental status). Thirty patients were found to be infected. Clinical diagnosis differentiated infected and non-infected patients with only 61.5% accuracy (sensitivity 60.3%; specificity 64.4%; p = 0.0049). Concordance between physicians was poor (κ = 0.33). Providers were able to predict the infectious source correctly only 60% of the time. Utilization of culture/objective data and SICU antibiotic protocols led to overall 78% appropriate initiation of antibiotics compared with 48% when treatment was based on clinical evaluation alone. Conclusion: Clinical diagnosis of infection is difficult, inaccurate, and unreliable in the absence of culture and sensitivity data. Infection suspected on the basis of signs and symptoms should be confirmed via objective and thorough work-up.

Macroeconomic trends and practice models impacting acute care surgery.

Acute care surgery (ACS) diagnoses are responsible for approximately a quarter of the costs of inpatient care in the US government, and individuals will be responsible for a larger share of the costs of this healthcare as the population ages. ACS as a specialty thus has the opportunity to meet a significant healthcare need, and by optimizing care delivery models do so in a way that improves both quality and value. ACS practice models that have maintained or added emergency general surgery (EGS) and even elective surgery have realized more operative case volume and surgeon satisfaction. However, vulnerabilities exist in the ACS model. Payer mix in a practice varies by geography and distribution of EGS, trauma, critical care, and elective surgery. Critical care codes constitute approximately 25% of all billing by acute care surgeons, so even small changes in reimbursement in critical care can have significant impact on professional revenue. Staffing an ACS practice can be challenging depending on reimbursement and due to uneven geographic distribution of available surgeons. Empowered by an understanding of economics, using team-oriented leadership inherent to trauma surgeons, and in partnership with healthcare organizations and regulatory bodies, ACS surgeons are positioned to significantly influence the future of healthcare in the USA.

Significant Reduction of Pulmonary Embolism in Orthopaedic Trauma Patients.

OBJECTIVES: To report results of a protocol to lessen incidence of pulmonary embolism (PE) among orthopaedic trauma patients. DESIGN: Retrospective review. SETTING: Level 1 trauma center. PATIENT/PARTICIPANTS: Orthopaedic trauma inpatients were included in the study. INTERVENTION: On arrival, an orthopaedic trauma patient's PE risk is calculated using a previously developed tool. If possible, patients at high risk are given their first dose of enoxaparin before leaving the emergency room. If other injuries preclude enoxaparin, then chemoprophylaxis is held for 24 hours. Twenty-four hours after arrival, the patient's ability to receive enoxaparin is reassessed. If possible, enoxaparin is started, with dosing twice a day. If enoxaparin is still contraindicated, a removable inferior vena cava filter is placed. Adequacy of enoxaparin dosing is tested using anti-factor Xa assay, drawn 4 hours after the third dose of enoxaparin. If the anti-factor Xa result is less than 0.2 IU/mL, a removable inferior vena cava filter is placed. If the result is 0.2-0.5 IU/mL, enoxaparin dosing is continued. If greater than 0.5 IU/mL, the dose of enoxaparin is reduced. OUTCOME MEASURE: The main outcome measure was rate of PE. RESULTS: From September 1, 2015 to December 31, 2015, our hospital admitted 420 orthopaedic trauma patients. Fifty-one patients were classed as high risk for PE. In September through December 2015, 9 sustained PE, 1 of which was fatal. From September 1, 2016 to December 31, 2016, our hospital admitted 368 orthopaedic trauma patients with comparable age and Injury Severity Score to 2015. Forty patients were at high risk for PE, 1 sustained a nonfatal PE. PE incidence from September to December 2016 was significantly lower than in 2015 (P = 0.02). Overall, 26 patients managed under the new protocol had IVCFs placed, 21 had their filters removed, and 3 died with filters in place. There were no complications during filter placement or removal. One patient had hemorrhage felt to be attributable to enoxaparin. CONCLUSIONS: Our protocol emphasizes more robust enoxaparin dosing, and more frequent use of IVCF, but only among those at high risk. We lessened the incidence of PE, with a low complication rate. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Prospective validation of the Parkland Grading Scale for Cholecystitis.

BACKGROUND: The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes. METHODS: Eleven surgeons took pictures of and prospectively graded the initial view of 317 GBs using PGS while performing LC (LIVE) between 9/2016 and 3/2017. Three independent surgeon raters retrospectively graded these saved GB images (STORED). The Intraclass Correlation Coefficient (ICC) statistic assessed rater reliability. Fisher's Exact, Jonckheere-Terpstra, or ANOVA tested association between peri-operative data and gallbladder grade. RESULTS: ICC between LIVE and STORED PGS grades demonstrated excellent reliability (ICC = 0.8210). Diagnosis of acute cholecystitis, difficulty of surgery, incidence of partial and open cholecystectomy rates, pre-op WBC, length of operation, and bile leak rates all significantly increased with increasing grade. CONCLUSIONS: PGS is a highly reliable, simple, operative based scale that can accurately predict outcomes after LC. TABLE OF CONTENTS SUMMARY: The Parkland Grading Scale for Cholecystitis was found to be a reliable and accurate predictor of laparoscopic cholecystectomy outcomes. Diagnosis of acute cholecystitis, surgical difficulty, incidence of partial and open cholecystectomy rates, pre-op WBC, operation length, and bile leak rates all significantly increased with increasing grade.

The economic footprint of acute care surgery in the United States: Implications for systems development.

BACKGROUND: Acute care surgery (ACS) comprises trauma, surgical critical care, and emergency general surgery (EGS), encompassing both operative and nonoperative conditions. While the burden of EGS and trauma has been separately considered, the global footprint of ACS has not been fully characterized. We sought to characterize the costs and scope of influence of ACS-related conditions. We hypothesized that ACS patients comprise a substantial portion of the US inpatient population. We further hypothesized that ACS patients differ from other surgical and non-surgical patients across patient characteristics. METHODS: We queried the National Inpatient Sample 2014, a nationally representative database for inpatient hospitalizations. To capture all adult ACS patients, we included adult admissions with any International Classification of Diseases-9th Rev.-Clinical Modification diagnosis of trauma or an International Classification of Diseases-9th Rev.-Clinical Modification diagnosis for one of the 16 AAST-defined EGS conditions. Weighted patient data were presented to provide national estimates. RESULTS: Of the 29.2 million adult patients admitted to US hospitals, approximately 5.9 million (20%) patients had an ACS diagnosis. ACS patients accounted for US $85.8 billion, or 25% of total US inpatient costs (US $341 billion). When comparing ACS to non-ACS inpatient populations, ACS patients had higher rates of health care utilization with longer lengths of stay (5.9 days vs. 4.5 days, p < 0.001), and higher mean costs (US $14,466 vs. US $10,951, p < 0.001. Of all inpatients undergoing an operative procedure, 27% were patients with an ACS diagnosis. Overall, 3,186 (70%) of US hospitals cared for both trauma and EGS patients. CONCLUSION: Acute care surgery patients comprise 20% of the inpatient population, but 25% of total inpatient costs in the United States. In addition to being costly, they overall have higher health care utilization and worse outcomes. This suggests that there is an opportunity to improve clinical trajectory for ACS patients that in turn, can affect the overall US health care costs. LEVEL OF EVIDENCE: Epidemiologic, level III.

Variations of the lung microbiome and immune response in mechanically ventilated surgical patients.

Mechanically ventilated surgical patients have a variety of bacterial flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To address this clinical problem, the microbiome profile and host inflammatory response in bronchoalveolar lavage samples from the surgical intensive care unit were examined relative to clinical pathology diagnoses. The hypothesis was tested that clinical diagnosis of respiratory tract flora were similar to culture positive lavage samples in both microbiome and inflammatory profile. Bronchoalveolar lavage samples were collected in the surgical intensive care unit as standard of care for intubated individuals with a clinical pulmonary infection score of >6 or who were expected to be intubated for >48 hours. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel. The microbiome of the samples was sequenced for the 16S rRNA region using the Ion Torrent. Microbiome diversity analysis showed the culture-positive samples had the lowest levels of diversity and culture negative with the highest based upon the Shannon-Wiener index (culture positive: 0.77 ± 0.36, respiratory tract flora: 2.06 ± 0.73, culture negative: 3.97 ± 0.65). Culture-negative samples were not dominated by a single bacterial genera. Lavages classified as respiratory tract flora were more similar to the culture-positive in the microbiome profile. A comparison of cytokine expression between groups showed increased levels of cytokines (IFN-g, IL-17F, IL-1B, IL-31, TNF-a) in culture-positive and respiratory tract flora groups. Culture-positive samples exhibited a more robust immune response and reduced diversity of bacterial genera. Lower cytokine levels in culture-negative samples, despite a greater number of bacterial species, suggest a resident nonpathogenic bacterial community may be indicative of a normal pulmonary environment. Respiratory tract flora samples were most similar to the culture-positive samples and may warrant classification as culture-positive when considering clinical treatment.

Beclin-1-Dependent Autophagy Protects the Heart During Sepsis.

BACKGROUND: Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. METHODS: Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. RESULTS: LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mammalian target of rapamycin activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mammalian target of rapamycin signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for beclin 1 resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial danger-associated molecular patterns, and promoted mitophagy via PTEN-induced putative kinase 1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, attenuated inflammation, and rescued the phenotypes caused by beclin 1 deficiency in LPS-challenged mice. CONCLUSIONS: These results suggest that Beclin-1 protects the heart during sepsis and that the targeted induction of Beclin-1 signaling may have important therapeutic potential.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Can CT imaging of the chest, abdomen, and pelvis identify all vertebral injuries of the thoracolumbar spine without dedicated reformatting?

BACKGROUND: The main objective of this study was to compare detection rates of clinically significant thoracolumbar spine (TLS) fracture between computed tomography (CT) imaging of the chest, abdomen, and spine (CT CAP) and CT for the thoracolumbar spine (CT TL). METHODS: We retrospectively identified patients at our institution with a TLS fracture over a two-year period that had both CT CAP and reformatted CT TL imaging. The sensitivity of CT CAP to identify fracture was calculated for each fracture type. RESULTS: A total of 516 TLS fractures were identified in 125 patients using reformatted CT TL spine imaging. Overall, 69 of 512 fractures (13%) were missed on CT CAP that were identified on CT TL. Of those, there were no clinically significant missed fractures. CONCLUSIONS: CT CAP could potentially be used as a screening tool for clinically significant TLS injuries.