In-person radiologist to review the trauma panscan: a high-fidelity simulation training program for radiology trainees at an academic level 1 trauma center.

BACKGROUND: Radiology trainees were uncomfortable going to the CT scanner to review trauma panscans and interacting with trauma surgeons. OBJECTIVE: This study aims to determine if radiology residents can be trained to accurately identify injuries requiring immediate surgical attention at the CT scanner. METHODS: A high-fidelity simulation model was created to provide an immersive training experience. Between February 2015 and April 2017, 62 class 1 trauma panscans were read at the CT scanner by 11 PGY-3 radiology residents. Findings made at the scanner were compared to resident preliminary and attending radiology reports and correlated with clinical outcomes. Timestamps were recorded and analyzed. Surveys were administered to assess the impact of training on radiology residents' self-confidence and to assess trauma surgeons' preference for radiology at the scanner. Significance level was set at p < 0.05. RESULTS: The mean time to provide results at the CT scanner was 11.1 min. Mean time for the preliminary report for CT head and cervical spine was 24.4 ± 9.8 min, and for the CT chest, abdomen, and pelvis was 16.3 ± 6.9 min. 53 traumatic findings on 62 panscans were identified at the scanner and confirmed at preliminary and final reports, for a concordance rate of 85%, compared to 72% for the control group. Radiology residents agreed or strongly agreed the training prepared them for trauma panscan reporting. Trauma surgeons shifted in favor of radiology presence at the scanner. CONCLUSION: Radiology residents can be trained to accurately and rapidly identify injuries requiring immediate surgical attention at the CT scanner. CLINICAL IMPACT: These findings support the value-added of an in-person radiologist at the CT scanner for whole-body trauma panscans to facilitate timely detection of life-threatening injuries and improve professional relations between radiologists and trauma surgeons.

Impact of Obesity on Tranexamic Acid Efficacy in Adult Patients With Major Bleeding.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic used for prophylaxis and treatment of acute bleeding. Although fixed dosing is often used in practice, weight-based dosing is sometimes used in the operating room (OR). The efficacy and safety of fixed-dose TXA is not well established in patients with above average weight or body mass index. OBJECTIVE: To characterize the efficacy and safety of intravenous TXA in obese patients with major bleeding. METHODS: This was a retrospective review of 165 patients receiving fixed-dose TXA for acute bleeding outside the OR. Blood product administration (BPA) before and after TXA was collected, along with demographic and bleed-related information. Thrombotic events were the major safety end point. A prespecified subgroup analysis was conducted in patients weighing at least 100 kg compared with a lower weight. Logistic regression was performed to determine whether an association exists between body weight and blood product requirement after TXA administration. RESULTS: In the 24 hours after TXA, patients received an average of 4.17 units of blood product. Patients weighing at least 100 kg averaged 4.04 total units, compared with 4.19 units in the lower weight group (P = 0.603). Administration of individual blood products did not differ between groups, and thrombotic events were similar. Regression analysis did not associate weight with total BPA. CONCLUSION AND RELEVANCE: In patients receiving fixed-dose TXA, weight does not appear to alter blood product requirements or rates of adverse thrombotic events. These data support continued use of fixed-dose TXA for treatment of acute major bleeding in obese patients.

Toward a hemorrhagic trauma severity score: fusing five physiological biomarkers.

BACKGROUND: To introduce the Hemorrhage Intensive Severity and Survivability (HISS) score, based on the fusion of multi-biomarker data; glucose, lactate, pH, potassium, and oxygen tension, to serve as a patient-specific attribute in hemorrhagic trauma. MATERIALS AND METHODS: One hundred instances of Sensible Fictitious Rationalized Patient (SFRP) data were synthetically generated and the HISS score assigned by five clinically active physician experts (100 [5]). The HISS score stratifies the criticality of the trauma patient as; low(0), guarded(1), elevated(2), high(3) and severe(4). Standard classifier algorithms; linear support vector machine (SVM-L), multi-class ensemble bagged decision tree (EBDT), artificial neural network with bayesian regularization (ANN:BR) and possibility rule-based using function approximation (PRBF) were evaluated for their potential to similarly classify and predict a HISS score. RESULTS: SVM-L, EBDT, ANN:BR and PRBF generated score predictions with testing accuracies (majority vote) corresponding to 0.91 ± 0.06, 0.93 ± 0.04, 0.92 ± 0.07, and 0.92 ± 0.03, respectively, with no statistically significant difference (p > 0.05). Targeted accuracies of 0.99 and 0.999 could be achieved with SFRP data size and clinical expert scores of 147[7](0.99) and 154[9](0.999), respectively. CONCLUSIONS: The predictions of the data-driven model in conjunction with an adjunct multi-analyte biosensor intended for point-of-care continual monitoring of trauma patients, can aid in patient stratification and triage decision-making.

Electroporation-mediated delivery of FER gene enhances innate immune response and improves survival in a murine model of pneumonia.

Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae. After inoculation, a plasmid encoding human FER was delivered by EP into the lung (PNA/pFER-EP). Survival of FER-treated vs. controls (PNA; PNA/EP-pcDNA) was recorded. In parallel cohorts, bronchial alveolar lavage (BAL) and lung were harvested at 24 and 72 h with markers of infection measured. FER-EP-treated animals reduced bacterial counts and had better 5-day survival compared to controls (80 vs. 20 vs. 25%; p < 0.05). Pre-treatment resulted in 100% survival. With FER, inflammatory monocytes were quickly recruited into BAL. These cells had increased surface expression for Toll-receptor 2 and 4, and increased phagocytic and myeloperoxidase activity at 24 h. Samples from FER electroporated animals had increased phosphorylation of STAT transcription factors, varied gene expression of IL1ß, TNFα, Nrf2, Nlrp3, Cxcl2, HSP90 and increased cytokine production of TNF-α, CCL-2, KC, IFN-γ, and IL-1RA. In a follow-up experiment, using Methicillin-resistant Staphylococcus aureus (MRSA) similar bacterial reduction effects were obtained with FER gene delivery. We conclude that FER overexpression improves survival through STAT activation enhancing innate immunity and accelerating bacterial clearance in the lung. This constitutes a novel mechanism of inflammatory regulation with therapeutic potential in the setting of hospital-acquired pneumonia.

Molecular Characterization of Hypoxic Alveolar Epithelial Cells After Lung Contusion Indicates an Important Role for HIF-1α.

OBJECTIVE: To understand the fate and regulation of hypoxic type II alveolar epithelial cells (AECs) after lung contusion (LC). BACKGROUND: LC due to thoracic trauma is a major risk factor for the development of acute respiratory distress syndrome. AECs have recently been implicated as a primary driver of inflammation in LC. The main pathological consequence of LC is hypoxia, and a key mediator of adaptation to hypoxia is hypoxia-inducible factor (HIF)-1. We have recently published that HIF-1α is a major driver of acute inflammation after LC through type II AEC. METHODS: LC was induced in wild-type mice (C57BL/6), luciferase-based hypoxia reporter mice (ODD-Luc), and HIF-1α conditional knockout mice. The degree of hypoxia was assessed using hypoxyprobe and in vivo imaging system. The fate of hypoxic AEC was evaluated by luciferase dual staining with caspases-3 and Ki-67, terminal deoxynucleotidyl transferase dUTP nick end labeling, and flow cytometry with ApoStat. NLRP-3 expression was determined by western blot. Laser capture microdissection was used to isolate AECs in vivo, and collected RNA was analyzed by Q-PCR for HIF-related pathways. RESULTS: Global hypoxia was present after LC, but hypoxic foci were not uniform. Hypoxic AECs preferentially undergo apoptosis. There were significant reductions in NLRP-3 in HIF-1α conditional knockout mice. The expression of proteins involved in HIF-related pathways and inflammasome activation were significantly increased in hypoxic AECs. CONCLUSIONS: These are the first in vivo data to identify, isolate, and characterize hypoxic AECs. HIF-1α regulation through hypoxic AECs is critical to the initiation of acute inflammation after LC.

Double-Stranded RNA Interacts With Toll-Like Receptor 3 in Driving the Acute Inflammatory Response Following Lung Contusion.

OBJECTIVES: Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. We set to determine the role of toll-like receptor 3 and the binding of double-stranded RNA in the pathogenesis of sterile injury following lung contusion. DESIGN: Toll-like receptor 3 expression was analyzed in postmortem lung samples from patients with lung contusion. Unilateral lung contusion was induced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-ß (-/-), and wild-type mice. Subsequently, lung injury and inflammation were evaluated. Apoptotic indices, phagocytic activity, and phenotypic characterization of the macrophages were determined. Double-stranded RNA in bronchoalveolar lavage and serum samples following lung contusion was measured. A toll-like receptor 3/double-stranded RNA ligand inhibitor was injected into wild-type mice prior to lung contusion. MEASUREMENTS AND MAIN RESULTS: Toll-like receptor 3 expression was higher in patients and wild-type mice with lung contusion. The degree of lung injury, inflammation, and macrophage apoptosis was reduced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-ß (-/-), and wild-type mice with toll-like receptor 3 antibody neutralization. Alveolar macrophages from toll-like receptor 3 (-/-) mice had a lower early apoptotic index, a predominant M2 phenotype and increased surface translocation of toll-like receptor 3 from the endosome to the surface. When compared with viral activation pathways, lung injury in lung contusion demonstrated increased p38 mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 phosphorylation with inflammasome activation without a corresponding increase in nuclear factor-κB or type-1 interferon production. Additionally, pretreatment with toll-like receptor 3/double-stranded RNA ligand inhibitor led to a reduction in injury, inflammation, and macrophage apoptosis. CONCLUSIONS: We conclude that the interaction of double-stranded RNA from injured cells with toll-like receptor 3 drives the acute inflammatory response following lung contusion.

Improvement in acute care surgery medical student education and clerkships: use of feedback and loop closure.

BACKGROUND: The unpredictable and sometimes chaotic environment present in acute care surgery services (trauma, burn, surgical critical care, and nontrauma emergency surgery) can cause high levels of anxiety and stress that could impact a medical students' experience during their third year of medical school surgical clerkship. This negative perception perhaps is a determinant influence in diverting talented students into other medical subspecialties. We sought out to objectively identify potential areas of improvement through direct feedback and implement programmatic changes to address these areas. We hypothesized that as the changes were made, students' perception of the rotation would improve. MATERIALS AND METHODS: Review of end of clerkship third year of medical school trauma burn surgery rotation evaluations and comments was performed for the 2010-2011 academic year. Trends in negative feedback were identified and categorized into five areas for improvement as follows: logistics, student expectations, communication, team integration, and feedback. A plan was designed and implemented for each category. Feedback on improvements to the rotation was monitored via surveys and during monthly end of rotation face-to-face student feedback sessions with the rotation faculty facilitator and surgery clerkship director. Data were compiled and reviewed. RESULTS: Perceptions of the rotation markedly improved within the first month of the changes and continued to improve over the study time frame (2011-2013) in all five categories. We also observed an increase in the number of students selecting a surgical residency in the National Resident Matching Program match from a low of 8% in 2009-2010 before any interventions to 25% after full implementation of the improvement measures in 2011-2012. CONCLUSIONS: A systematic approach using direct feedback from students to address service-specific issues improves perceptions of students on the educational value of a busy trauma-burn acute care surgery service and may have a positive influence on students considering surgical careers to pursue a surgical specialty.

Activation of hypoxia-inducible factor-1α in type 2 alveolar epithelial cell is a major driver of acute inflammation following lung contusion.

OBJECTIVE: Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. Hypoxia-inducible factor-1α is the primary transcription factor that is responsible for regulating the cellular response to changes in oxygen tension. We set to determine if hypoxia-inducible factor-1α plays a role in the pathogenesis of acute inflammatory response and injury in lung contusion. DESIGN: Nonlethal closed-chest unilateral lung contusion was induced in a hypoxia reporter mouse model and type 2 cell-specific hypoxia-inducible factor-1α conditional knockout mice. The mice were killed at 5-, 24-, 48-, and 72-hour time points, and the extent of systemic and tissue hypoxia was assessed. In addition, injury and inflammation were assessed by measuring bronchoalveolar lavage cells (flow cytometry and cytospin), albumin (permeability injury), and cytokines (inflammation). Isolated type 2 cells from the hypoxia-inducible factor-1α conditional knockout mice were isolated and evaluated for proinflammatory cytokines following lung contusion. Finally, the role of nuclear factor-κB and interleukin-1ß as intermediates in this interaction was studied. RESULTS: Lung contusion induced profound global hypoxia rapidly. Increased expression of hypoxia-inducible factor-1α from lung samples was observed as early as 60 minutes, following the insult. The extent of lung injury following lung contusion was significantly reduced in conditional knockout mice at all the time points, when compared with the wild-type littermate mice. Release of proinflammatory cytokines, such as interleukin-1ß, interleukin-6, macrophage inflammatory protein-2, and keratinocyte chemoattractant, was significantly lower in conditional knockout mice. These actions are in part mediated through nuclear factor-κB. Hypoxia-inducible factor-1α in lung epithelial cells was shown to regulate interleukin-1ß promoter activity. CONCLUSION: Activation of hypoxia-inducible factor-1α in type 2 cell is a major driver of acute inflammation following lung contusion.

Beyond American College of Surgeons Verification: Quality Metrics Associated with High Performance at Level I and II Trauma Centers.

INTRODUCTION: The American College of Surgeons (ACS) Committee on Trauma has established a framework for trauma center quality improvement. Despite efforts, recent studies show persistent variation in patient outcomes across national trauma centers. We aimed to investigate whether risk-adjusted mortality varies at the hospital level and if high-performing centers demonstrate better adherence to ACS Verification, Review, and Consultation (VRC) program quality measures. METHODS: We analyzed data from the 2018-2021 ACS TQIP Participant Use Files, focusing on adult admissions at ACS-verified Level I or II trauma centers for blunt, penetrating, or isolated traumatic brain injury. We used mixed-effects models to assess center-specific risk-adjusted mortality and identified high-performing centers (HPTC), defined as those with the lowest decile of overall risk-adjusted mortality. We compared patient and hospital characteristics, outcomes, and adherence to ACS-VRC quality measures between HPTC and non-HPTC. RESULTS: Over the study period, 1,498,602 patients across 442 Level I and II trauma centers met inclusion criteria: 65.3% presenting with blunt injury, 9.3% with penetrating injury, and 25.4% with isolated TBI. Management at HPTC was associated with lower odds of major complications, failure-to-rescue and takeback. Furthermore, HPTC status was associated with increased odds of adherence to several ACS-VRC quality measures, including balanced resuscitation (Odds Ratio [OR] 1.40, 95%Confidence Interval [CI] 1.29-1.51), appropriate pediatric admissions (OR 1.88, 95%CI 1.07-3.68), and substance abuse screening (AOR 1.14, 95%CI 1.12-1.16). CONCLUSION: Significant variation in risk-adjusted mortality persists across trauma centers. Given the association between adherence to quality measures and high-performance, multidisciplinary efforts to refine and implement guidelines are warranted.

Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.

Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2(-/-) mice when compared with the wild-type (WT) mice. We also found increased release of IL-1ß, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2(-/-) mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2(-/-) mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.

Different Surgeon, Different Duration: Lack of Consensus on the Appropriate Duration of Antimicrobial Prophylaxis and Therapy in Surgical Practice.

Background: The principles of antimicrobial stewardship promote the appropriate prescribing of agents with respect to efficacy, safety, duration, and cost. Antibiotic resistance often results from inappropriate use (e.g., indication, selection, duration). We evaluated practice variability in duration of antimicrobials in surgical infection treatment (Rx) or prophylaxis (Px). Hypothesis: There is lack of consensus regarding the duration of antibiotic Px and Rx for many common indications. Methods: A survey was distributed to the Surgical Infection Society (SIS) regarding the use of antimicrobial agents for a variety of scenarios. Standard descriptive statistics were used to compare survey responses. Heterogeneity among question responses were compared using the Shannon Index, expressed as natural units (nats). Results: Sixty-three SIS members responded, most of whom (67%) have held a leadership position within the SIS or contributed as an annual meeting moderator or discussant; 76% have been in practice for more than five years. Regarding peri-operative Px, more than 80% agreed that a single dose is adequate for most indications, with the exceptions of gangrenous cholecystitis (40% single dose, 38% pre-operative +24 hours) and inguinal hernia repair requiring a bowel resection (70% single dose). There was more variability regarding the use of antibiotic Px for various bedside procedures with respondents split between none needed (range, 27%-66%) versus a single dose (range, 31%-67%). Opinions regarding the duration of antimicrobial Rx for hospitalized patients who have undergone a source control operation or procedure varied widely based on indication. Only two of 20 indications achieved more than 60% consensus despite available class 1 evidence: seven days for ventilator-associated pneumonia (77%), and four plus one days for perforated appendicitis (62%). Conclusions: Except for peri-operative antibiotic Px, there is little consensus regarding antibiotic duration among surgical infection experts, despite class 1 evidence and several available guidelines. This highlights the need for further high-level research and better dissemination of guidelines.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. Design, Setting, and Participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. Interventions: Appendectomy vs antibiotics. Main Outcomes and Measures: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. Results: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, -1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. Conclusions and Relevance: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Surgical Infection Society Research Priorities: A Narrative Review of Fourteen Years of Progress.

Background: In 2006, the Surgical Infection Society (SIS) utilized a modified Delphi approach to define 15 specific priority research questions that remained unanswered in the field of surgical infections. The aim of the current study was to evaluate the scientific progress achieved during the ensuing period in answering each of the 15 research questions and to determine if additional research in these fields is warranted. Methods: For each of the questions, a literature search using the National Center for Biotechnology Information (NCBI) was performed by the Scientific Studies Committee of the SIS to identify studies that attempted to address each of the defined questions. This literature was analyzed and summarized. The data on each question were evaluated by a surgical infections expert to determine if the question was answered definitively or remains unanswered. Results: All 15 priority research questions were studied in the last 14 years; six questions (40%) were definitively answered and 9 questions (60%) remain unanswered in whole or in part, mainly because of the low quality of the studies available on this topic. Several of the 9 unanswered questions were deemed to remain research priorities in 2020 and warrant further investigation. These included, for example, the role of empiric antimicrobial agents in nosocomial infections, the use of inotropes/vasopressors versus volume loading to raise the mean arterial pressure, and the role of increased antimicrobial dosing and frequency in the obese patient. Conclusions: Several surgical infection-related research questions prioritized in 2006 remain unanswered. Further high-quality research is required to provide a definitive answer to many of these priority knowledge gaps. An updated research agenda by the SIS is warranted at this time to define research priorities for the future.

Resonance Raman Spectroscopy Derived Tissue Hemoglobin Oxygen Saturation in Critically Ill and Injured Patients.

BACKGROUND: In this study, we examined the ability of resonance Raman spectroscopy to measure tissue hemoglobin oxygenation (R-StO2) noninvasively in critically ill patients and compared its performance with conventional central venous hemoglobin oxygen saturation (ScvO2). METHODS: Critically ill patients (n = 138) with an indwelling central venous or pulmonary artery catheter in place were consented and recruited. R-StO2 measurements were obtained by placing a sensor inside the mouth on the buccal mucosa. R-StO2 was measured continuously for 5 min. Blood samples were drawn from the distal port of the indwelling central venous catheter or proximal port of the pulmonary artery catheter at the end of the test period to measure ScvO2 using standard co-oximetry analyzer. A regression algorithm was used to calculate the R-StO2 based on the observed spectra. RESULTS: Mean (SD) of pooled R-StO2 and ScvO2 were 64(7.6) % and 65(9.2) % respectively. A paired t test showed no significant difference between R-StO2 and ScvO2 with a mean(SD) difference of -1(7.5) % (95% CI: -2.2, 0.3%) with a Clarke Error Grid demonstrating 84.8% of the data residing within the accurate and acceptable grids. Area under the receiver operator curve for R-StO2's was 0.8(0.029) (95% CI: 0.7, 0.9 P < 0.0001) at different thresholds of ScvO2 (≤60%, ≤65%, and ≤70%). Clinical adjudication by five clinicians to assess the utility of R-StO2 and ScvO2 yielded Fleiss' Kappa agreement of 0.45 (P < 0.00001). CONCLUSIONS: R-StO2 has the potential to predict ScvO2 with high precision and might serve as a faster, safer, and noninvasive surrogate to these measures.

Surgical Infections and the Future of Research: Re-Defining the Research Agenda for the Surgical Infection Society.

Background: Infections represent a major component of surgical practice. Risk mitigation, seeking eradication and optimal patient outcomes, require a concerted, multifocal effort to understand disease and microbiology, prevent infections, and treat them. The present study was undertaken to re-define the Surgical Infection Society (SIS) research agenda for the next decade. Hypothesis: We utilized the expertise of the SIS membership to identify research questions regarding surgical infections, hypothesizing that consensus among participants could be used to re-define the future research agenda. Methods: Members of the SIS were surveyed using a modified Delphi. The three rounds of the survey were targeted at: question generation; question ranking; and reaching consensus. Each of the 15 questions to emerge was evaluated according to level of consensus, feasibility, and data availability. Results: One hundred twenty-four participants contributed. Initially, 226 questions were generated that were condensed to 35 unique questions for consideration in the subsequent two rounds. The 35 questions encompassed several research themes, with antibiotic prophylaxis (n = 8), prevention of surgical site infections (SSIs; n = 6), and improved diagnostics (n = 5) being most common. Standard deviation of importance scores was inversely proportional to the question rank, indicating greater consensus among higher ranking questions. All 15 questions had a feasibility score of greater than three (five-point Likert scale), and the majority (12/15) had a mean data availability score of less than three. In the final round of the survey, the top three topics for further research surrounded non-antimicrobial treatments, optimal treatment duration for bacteremia, and treatment duration for necrotizing soft tissue infections. Conclusions: Using a modified Delphi process, 15 research questions addressing surgical infections were identified. Such questions can assist the SIS and the SIS Foundation for Research and Education in prioritizing and enabling research efforts, and development of a strategic research plan for the next decade.

One-Year Functional, Cognitive, and Psychological Outcomes Following the Use of Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019: A Prospective Study.

To prospectively describe 1-year outcomes, with a focus on functional outcome, cognitive outcome, and the burden of anxiety, depression, and post-traumatic stress disorder, in coronavirus disease 2019 patients managed with extracorporeal membrane oxygenation. DESIGN: Prospective case series. SETTING: Tertiary extracorporeal membrane oxygenation center in the United States. PATIENTS: Adult coronavirus disease 2019 acute respiratory distress syndrome patients managed with extracorporeal membrane oxygenation March 1, 2020, to July 31, 2020. INTERVENTIONS: Baseline variables, treatment measures, and short-term outcomes were obtained from the medical record. Survivors were interviewed by telephone, a year following the index intensive care admission. Functional outcome was assessed using the modified Rankin Scale and the World Health Organization Disability Assessment Scale 2.0. Cognitive status was assessed with the 5-minute Montreal Cognitive Assessment. The Hospital Anxiety and Depression Scale was used to screen for anxiety and depression. Screening for post-traumatic stress disorder was performed with the Posttraumatic Stress Disorder Checklist 5 instrument. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients were managed with extracorporeal membrane oxygenation, 14 (61%) survived to hospital discharge. Thirteen (57%) were alive at 1 year. One patient was dependent on mechanical ventilation, another intermittently required supplemental oxygen at 1 year. The median modified Rankin Scale score was 2 (interquartile range, 1-2), median World Health Organization Disability Assessment Scale 2.0 impairment score was 21% (interquartile range, 6-42%). Six of 12 previously employed individuals (50%) had returned to work, and 10 of 12 (83%) were entirely independent in activities of daily living. The median Montreal Cognitive Assessment score was 14 (interquartile range, 13-14). Of 10 patients assessed with Hospital Anxiety and Depression Scale, 4 (40%) screened positive for depression and 6 (60%) for anxiety. Four of 10 (40%) screened positive for post-traumatic stress disorder. CONCLUSIONS: Functional impairment was common a year following the use of extracorporeal membrane oxygenation in coronavirus disease 2019, although the majority achieved independence in daily living and about half returned to work. Long-term anxiety, depression, and post-traumatic stress disorder were common, but cognitive impairment was not.