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.

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.

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.

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.

STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery.

INTRODUCTION: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. METHODS: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. RESULTS: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. CONCLUSION: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

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.

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.

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.

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.

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.

Validation of the American Association for the Surgery of Trauma grading system for acute appendicitis severity.

OBJECTIVE: The American Association for the Surgery of Trauma (AAST) developed an anatomic grading system to assess disease severity through increasing grades of inflammation. Severity grading can then be utilized in risk-adjustment and stratification of patient outcomes for clinical benchmarking. We sought to validate the AAST appendicitis grading system by examining the ability of AAST grade to predict clinical outcomes used for clinical benchmarking. METHODS: Surgical quality program data were prospectively collected on all adult patients undergoing appendectomy for acute appendicitis at our institution between December 2013 and May 2018. The AAST acute appendicitis grade from 1 to 5 was assigned for all patients undergoing open or laparoscopic appendectomy. Primary outcomes were occurrence of major complications, any complications, and index hospitalization length of stay. Multivariable models were constructed for each outcome without and with inclusion of the AAST grade as an ordinal variable. We also developed models using International Classification of Diseases, 9th or 10th Rev.-Clinical Modification codes to determine presence of perforation for comparison. RESULTS: A total of 734 patients underwent appendectomy for acute appendicitis. The AAST score distribution included 561 (76%) in grade 1, 49 (6.7%) in grade 2, 79 (10.8%) in grade 3, 33 (4.5%) in grade 4, and 12 (1.6%) in grade 5. The mean age was 35.3 ± 14.7 years, 47% were female, 20% were nonwhite, and 69% had private insurance. Major complications, any complications, and hospital length of stay were all positively associated with AAST grade (p < 0.05). Risk-adjustment model fit improved after including AAST grade in the major complications, any complications, and length of stay multivariable regression models. The AAST grade was a better predictor than perforation status derived from diagnosis codes for all primary outcomes studied. CONCLUSION: Increasing AAST grade is associated with higher complication rates and longer length of stay in patients with acute appendicitis. The AAST grade can be prospectively collected and improves risk-adjusted modeling of appendicitis outcomes. LEVEL OF EVIDENCE: Prospective/Epidemiologic, Level III.

TLR3 absence confers increased survival with improved macrophage activity against pneumonia.

Toll-like receptor 3 (TLR3) is a pathogen recognition molecule associated with viral infection with double-stranded RNA (dsRNA) as its ligand. We evaluated the role of TLR3 in bacterial pneumonia using Klebsiella pneumoniae (KP). WT and TLR3-/- mice were subjected to a lethal model of KP. Alveolar macrophage polarization, bactericidal activity, and phagocytic capacity were compared. RNA-sequencing was performed on alveolar macrophages from the WT and TLR3-/- mice. Adoptive transfers of alveolar macrophages from TLR3-/- mice to WT mice with KP were evaluated for survival. Expression of TLR3 in postmortem human lung samples from patients who died from gram-negative pneumonia and pathological grading of pneumonitis was determined. Mortality was significantly lower in TLR3-/-, and survival improved in WT mice following antibody neutralization of TLR3 and with TLR3/dsRNA complex inhibitor. Alveolar macrophages from TLR3-/- mice demonstrated increased bactericidal and phagocytic capacity. RNA-sequencing showed an increased production of chemokines in TLR3-/- mice. Adoptive transfer of alveolar macrophages from the TLR3-/- mice restored the survival in WT mice. Human lung samples demonstrated a good correlation between the grade of pneumonitis and TLR3 expression. These data represent a paradigm shift in understanding the mechanistic role of TLR3 in bacterial pneumonia.

Complications and resource utilization in trauma patients with diabetes.

Diabetes is associated with poor outcomes in critically ill populations. The goal of this study was to determine if diabetic patients suffer poorer outcomes following trauma. Collaborative trauma patient data from 2012-2018 was analyzed. Patients with no signs-of-life, Injury Severity Score (ISS) <5, age <16 years, and hospitalization <1 day were excluded. Multivariable logistic and linear regression were used to compare patients with and without diabetes for selected outcomes. Risk-adjustment variables included demographics, physiology, comorbidities, and injury scoring. Of 106,141 trauma patients, 14,150 (13%) had diabetes. On admission, diabetes was associated with significantly increased risk of any, serious, infectious, urinary tract, sepsis, pneumonia, and cardiac complications. Diabetes was also associated with increased ventilator days (7.5 vs. 6.6 days, p = 0.003), intensive care unit days (5.8 vs. 5.3 days, p<0.001), and hospital length of stay (5.7 vs. 5.3 days, p<0.001). Subgroup analysis revealed the least injured diabetic category (ISS 5-15) suffered higher odds of hospital mortality and any, serious, infectious and cardiac complications. The association between diabetes, hospital mortality and complication rates in mild traumatic injury is independent of age. Trauma patients with diabetes experience higher rates of complications and resource utilization. The largest cohort of diabetics experience the least severe injuries and suffer the greatest in hospital mortality and complication rates. A better understanding of the physiologic derangements associated with diabetes is necessary to develop novel approaches to reduce excess trauma morbidity, mortality and resource consumption.