Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.

AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell-mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day-1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.

Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.

Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5 capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A. No FVIII inhibitors were detected following administration of valoctocogene roxaparvovec. Immune responses were predominantly directed toward the AAV5 capsid, with all participants developing durable anti-AAV5 antibodies. Cellular immune responses specific for the AAV5 capsid were detected in most participants by interferon-ᵧ enzyme-linked immunosorbent spot assay 2 weeks following dose administration and declined or reverted to negative over the first 52 weeks. These responses were weakly correlated with alanine aminotransferase elevations and showed no association with changes in FVIII activity. FVIII-specific cellular immune responses were less frequent and more sporadic compared with those specific for AAV5 and showed no association with safety or efficacy parameters.

Long-term safety and efficacy outcomes of valoctocogene roxaparvovec gene transfer up to 6 years post-treatment.

INTRODUCTION: Valoctocogene roxaparvovec uses an adeno-associated virus serotype 5 (AAV5) vector to transfer a factor VIII (FVIII) coding sequence to individuals with severe haemophilia A, providing bleeding protection. AIM: To assess safety and efficacy of valoctocogene roxaparvovec 5-6 years post-treatment. METHODS: In a phase 1/2 trial, adult male participants with severe haemophilia A (FVIII ≤1 IU/dL) without FVIII inhibitors or anti-AAV5 antibodies received valoctocogene roxaparvovec and were followed for 6 (6 × 1013 vg/kg; n = 7) and 5 (4 × 1013 vg/kg; n = 6) years. Safety, including investigation of potential associations between a malignancy and gene therapy, and efficacy are reported. RESULTS: No new treatment-related safety signals emerged. During year 6, a participant in the 6 × 1013  vg/kg cohort was diagnosed with grade 2 parotid gland acinar cell carcinoma; definitive treatment was uncomplicated parotidectomy with lymph node dissection. Target enrichment sequencing of tumour and adjacent healthy tissue revealed low vector integration (8.25 × 10-5 per diploid cell). Integrations were not elevated in tumour samples, no insertions appeared to drive tumorigenesis, and no clonal expansion of integration-containing cells occurred. During all follow-ups, >90% decreases from baseline in annualised treated bleeds and FVIII infusion rates were maintained. At the end of years 6 and 5, mean FVIII activity (chromogenic assay) was 9.8 IU/dL (median, 5.6 IU/dL) and 7.6 IU/dL (median, 7.1 IU/dL) for the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, representing proportionally smaller year-over-year declines than earlier timepoints. CONCLUSIONS: Valoctocogene roxaparvovec safety and efficacy profiles remain largely unchanged; genomic investigations showed no association with a parotid tumour.

Pain management in trauma: the need for trauma-informed opioid prescribing guidelines.

Background/objectives: Surgical populations and particularly injury survivors often present with complex trauma that elevates their risk for prolonged opioid use and misuse. Changes in opioid prescribing guidelines during the past several years have yielded mixed results for pain management after trauma, with a limiting factor being the heterogeneity of clinical populations and treatment needs in individuals receiving opioids. The present analysis illuminates this gap between clinical guidelines and clinical practice through qualitative feedback from hospital trauma providers and unit staff members regarding current opioid prescribing guidelines and practices in the setting of traumatic injury. Methods: The parent study aimed to implement a pilot screening tool for opioid misuse in four level I and II trauma hospitals throughout Wisconsin. As part of the parent study, focus groups were conducted at each study site to explore the facilitators and barriers of implementing a novel screening tool, as well as to examine the current opioid prescribing guidelines, trainings, and resources available for trauma and acute care providers. Focus group transcripts were independently coded and analyzed using a modified grounded theory approach to identify themes related to the facilitators and barriers of opioid prescribing guidelines in trauma and acute care. Results: Three major themes were identified as impactful to opioid-related prescribing and care provided in the setting of traumatic injury; these include (1) acute treatment strategies; (2) patient interactions surrounding pain management; and (3) the multifactorial nature of trauma on pain management approaches. Conclusion: Providers and staff at four Wisconsin trauma centers called for trauma-specific opioid prescribing guidelines in the setting of trauma and acute care. The ubiquitous prescription of opioids and challenges in long-term pain management in these settings necessitate additional community-integrated research to inform development of federal guidelines. Level of evidence: Therapeutic/care management, level V.

Is nonoperative management of appendicitis safe and effective in multi-morbid patients?

BACKGROUND: The purpose of this study was to (1) compare post-treatment outcomes of operative and nonoperative management of acute appendicitis in multi-morbid patients and (2) evaluate the generalizability of prior clinical trials by determining whether outcomes differ in multi-morbid patients compared to the young and healthy patients who resemble prior clinical trial participants. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample from 2004 to 2017. We included 368,537 patients with acute, uncomplicated appendicitis who were classified as having 0 or 2+ comorbidities. We compared inpatient morbidity, mortality, length of stay, and costs using propensity scores. Unmeasured confounding was addressed with probabilistic sensitivity analysis. RESULTS: Overall, 5% of patients without comorbidities were treated nonoperatively versus 20% of multi-morbid patients. Compared to surgery, nonoperative management was associated with a 3.5% decrease in complications (95% confidence interval 3%-4%) for multi-morbid patients, but there was no significant difference for patients without comorbidity. However, nonoperative management was associated with a 1.5% increase in mortality for multimorbid patients (95% confidence interval 1.3%-1.7%). Costs and length of stay were lower for all patients treated with surgery. Probabilistic sensitivity analysis showed that results were robust to the effects of unmeasured confounding. CONCLUSION: Our results raise concerns about the generalizability of clinical trials that compared nonoperative and operative management of appendicitis because (1) those trials enrolled mostly young and healthy patients, and (2) results in multi-morbid patients differ from outcomes in younger and healthier patients.

The Use of Parenteral Nutrition and Disparities in Its Allocation Following Traumatic Injury.

INTRODUCTION: Severe traumatic injury requires rapid and extensive deployment of resources to save the lives of the critically injured. The sequelae of traumatic injuries frequently require extensive intervention obligating patients to a complicated recovery process devoid of meaningful nutrition. In this setting, parenteral nutrition (PN) is key in enabling appropriate wound healing, recovery, and rehabilitation. We sought to examine the use of PN in adult trauma management and to highlight any disparities in the utilization of PN in adult trauma patients. METHODS: We queried the 2017-2019 Trauma Quality Improvement Program (TQIP) for adult patients (aged > 18 y) who sustained blunt or penetrating traumatic injuries and received PN as part of their hospitalization. We compared time to PN administration based on demographics. We then used a multivariable logistic regression model to identify factors associated with the use of PN. We hypothesized that PN would be less commonly employed in the uninsured and minority groups. RESULTS: We identified 2,449,498 patients with sufficient data for analysis. Of these, 1831 patients were treated with PN. On univariate analysis, PN patients were more commonly male (74.7% PN versus 60.2% non-PN; P < 0.001). PN use was more frequent in the Black population (24.3% PN versus 15.5% non-PN; P < 0.001) and less frequent in the White population (72.7% PN versus 81.2% non-PN; P < 0.001). PN use was also much more common among patients covered by Medicaid. Penetrating trauma was over twice as common among PN recipients relative to non-PN patients (% PN versus % non-PN). PN patients had higher injury severity scores (ISSs), more intensive care unit days, longer hospitalizations, and increased mortality compared to non-PN patients. PN patients were half as likely to discharge home and twice as likely to discharge to a long-term care facility. Multivariable analysis including age, race, trauma mechanism, primary payer, and ISS, demonstrated an association of PN use with increasing age (OR 1.01, P < 0.001), cases of penetrating trauma (odds ratio [OR], 2.47; P < 0.001), and patients with high ISS (OR, 0.1.06; P < 0.001). There was decreased use in Uninsured patient (OR, 0.54; P < 0.001). CONCLUSIONS: PN use following traumatic injury is rarely required. Patients treated with PN typically have a resource-intense hospital course. More severe injuries, penetrating trauma, and increased age are more likely to result in PN use. Variations in PN use are apparent based on insurance payer, further examination into allocation of hospital and intensive care resources, as it pertains to patient socioeconomic status, is warranted in light of these findings.

Current status of research on emergency surgery score in trauma patients: a bibliometric analysis.

Background: The use of a relevant emergency score can provide an accurate assessment of the patient's condition and prognosis. However, the status of related studies remains unclear. The current study analyzed the research status of emergency surgery score (ESS) of trauma patients by using bibliometric methods. Methods: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection (WOSCC) was searched using keywords "trauma" and "emergency surgery score". All records from the search results and cited references were exported to Excel, duplicate literature records were removed, information for the same author and organization in different signature forms were merged. The resulting literatures were analyzed by year of publication, citation, discipline, countries and research institutions, journals, authors, and use of keywords. The cooperation among countries, institutions, and authors was also examined. Results: A total of 2,175 document were retrieved. The number of published literature and the number of citations per year increased annually. The number of published documents (n=1,029) and research cooperation (centrality score, 0.44) in the United States were significantly ahead of those in other countries. The ten research institutions with the largest number of published documents were all from the United States, with much cooperation between research institutions and authors. There were many publications from China (n=108), but with few cooperations (centrality score, 0.22). The journals with the largest number of published articles were professional in the fields of trauma, emergency, and critical care. Keyword analysis showed that infection and shock were important issues besides surgery in the research related to ESS of trauma patients. Conclusions: Research related to ESS of trauma patients has been mainly conducted in the United States, and Chinese researchers should increase their level of cooperation.

Development of a prospective biliary dashboard to compare performance and surgical cost.

BACKGROUND: Transparency around surgeon level data may align healthcare delivery with quality care for patients. Biliary surgery includes numerous procedures performed by both general surgeons and subspecialists alike. Cholecystectomy is a common surgical procedure and an optimal cohort to measure quality outcomes within a healthcare system. METHODS: Data were collected for 5084 biliary operations performed by 68 surgeons in 11 surgical divisions in a health system including a tertiary academic hospital, two regional community hospitals, and two ambulatory surgery centers. A privacy protected dashboard was developed to compare surgeon performance and cost between July 2018 and June 2022. A sample cohort of patients ≥ 18 years who underwent cholecystectomy were compared by operative time, cost, and 30-day outcomes. RESULTS: Over 4 years, 4568 cholecystectomy procedures were performed by 57 surgeons. Operations were done by 57 surgeons in four divisions and included 3846 (84.2%) laparoscopic cholecystectomies, 601 (13.2%) laparoscopic cholecystectomies with cholangiogram, and 121 (2.6%) open cholecystectomies. Patients were admitted from the emergency room in 2179 (47.7%) cases while 2389 (52.3%) cases were performed in the ambulatory setting. Individual surgeons were compared to peers for volume, intraoperative data, cost, and outcomes. Cost was lowest at ambulatory surgery centers, yet only 4.2% of elective procedures were performed at these facilities. Prepackaged kits with indocyanine green were more expensive than cholangiograms that used iodinated contrast. The rate of emergency department visits was lowest when cases were performed at ambulatory surgery centers. CONCLUSION: Data generated from clinical dashboards can inform surgeons as to how they compare to peers regarding quality metrics such as cost, time, and complications. In turn, this may guide strategies to standardize care, optimize efficiency, provide cost savings, and improve outcomes for cholecystectomy procedures. Future application of clinical dashboards can assist surgeons and administrators to define value-based care.

Prospective, multicenter study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (XenMatrix™ AB Surgical Graft) for hernia repair in all centers for disease control and prevention wound classes: 24-month follow-up cohort.

Prospective, multicenter, single-arm study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (AC-PDM) in a cohort involving all centers for disease control and prevention wound classes in ventral/incisional midline hernia repair (VIHR). Materials and methods: Seventy-five patients (mean age 58.6±12.7 years; BMI 31.3±4.9 kg/m2) underwent ventral/incisional midline hernia repair with AC-PDM. Surgical site occurrence (SSO) was assessed in the first 45 days post-implantation. Length of stay, return to work, hernia recurrence, reoperation, quality of life, and SSO were assessed at 1, 3, 6, 12, 18, and 24 months. Results: 14.7% of patients experienced SSO requiring intervention within 45 days post-implantation, and 20.0% thereafter (>45 d post-implantation). Recurrence (5.8%), definitely device-related adverse events (4.0%), and reoperation (10.7%) were low at 24 months; all quality-of-life indicators were significantly improved compared to baseline. Conclusion: AC-PDM exhibited favourable results, including infrequent hernia recurrence and definitely device-related adverse events, with reoperation and SSO comparable to other studies, and significantly improved quality of life.

Quality care is equitable care: a call to action to link quality to achieving health equity within acute care surgery.

Health equity is defined as the sixth domain of healthcare quality. Understanding health disparities in acute care surgery (defined as trauma surgery, emergency general surgery and surgical critical care) is key to identifying targets that will improve outcomes and ensure delivery of high-quality care within healthcare organizations. Implementing a health equity framework within institutions such that local acute care surgeons can ensure equity is a component of quality is imperative. Recognizing this need, the AAST (American Association for the Surgery of Trauma) Diversity, Equity and Inclusion Committee convened an expert panel entitled 'Quality Care is Equitable Care' at the 81st annual meeting in September 2022 (Chicago, Illinois). Recommendations for introducing health equity metrics within health systems include: (1) capturing patient outcome data including patient experience data by race, ethnicity, language, sexual orientation, and gender identity; (2) ensuring cultural competency (eg, availability of language services; identifying sources of bias or inequities); (3) prioritizing health literacy; and (4) measuring disease-specific disparities such that targeted interventions are developed and implemented. A stepwise approach is outlined to include health equity as an organizational quality indicator.

Non-surgical management and analgesia strategies for older adults with multiple rib fractures: A systematic review, meta-analysis, and joint practice management guideline from the Eastern Association for the Surgery of Trauma and the Chest Wall Injury Society.

BACKGROUND: Chest wall injury in older adults is a significant cause of morbidity and mortality. Optimal nonsurgical management strategies for these patients have not been fully defined regarding level of care, incentive spirometry (IS), noninvasive positive pressure ventilation (NIPPV), and the use of ketamine, epidural, and other locoregional approaches to analgesia. METHODS: Relevant questions regarding older patients with significant chest wall injury with patient population(s), intervention(s), comparison(s), and appropriate selected outcomes were chosen. These focused on intensive care unit (ICU) admission, IS, NIPPV, and analgesia including ketamine, epidural analgesia, and locoregional nerve blocks. A systematic literature search and review were conducted, our data were analyzed qualitatively and quantitatively, and the quality of evidence was assessed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. No funding was used. RESULTS: Our literature review (PROSPERO 2020-CRD42020201241, MEDLINE, EMBASE, Cochrane, Web of Science, January 15, 2020) resulted in 151 studies. Intensive care unit admission was qualitatively not superior for any defined cohort other than by clinical assessment. Poor IS performance was associated with prolonged hospital length of stay, pulmonary complications, and unplanned ICU admission. Noninvasive positive pressure ventilation was associated with 85% reduction in odds of pneumonia ( p < 0.0001) and 81% reduction in odds of mortality ( p = 0.03) in suitable patients without risk of airway loss. Ketamine use demonstrated no significant reduction in pain score but a trend toward reduced opioid use. Epidural and other locoregional analgesia techniques did not affect pneumonia, length of mechanical ventilation, hospital length of stay, or mortality. CONCLUSION: We do not recommend for or against routine ICU admission. We recommend use of IS to inform ICU status and conditionally recommend use of NIPPV in patients without risk of airway loss. We offer no recommendation for or against ketamine, epidural, or other locoregional analgesia. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level IV.

Antibiotic prophylaxis for tube thoracostomy placement in trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma.

Background: Antibiotic prophylaxis is routinely administered for most operative procedures, but their utility for certain bedside procedures remains controversial. We performed a systematic review and meta-analysis and developed evidence-based recommendations on whether trauma patients receiving tube thoracostomy (TT) for traumatic hemothorax or pneumothorax should receive antibiotic prophylaxis. Methods: Published literature was searched through MEDLINE (via PubMed), Embase (via Elsevier), Cochrane Central Register of Controlled Trials (via Wiley), Web of Science and ClinicalTrials.gov databases by a professional librarian. The date ranges for our literature search were January 1900 to March 2020. A systematic review and meta-analysis of currently available evidence were performed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Results: Fourteen relevant studies were identified and analyzed. All but one were prospective, with eight being prospective randomized control studies. Antibiotic prophylaxis protocols ranged from a single dose at insertion to 48 hours post-TT removal. The pooled data showed that patients who received antibiotic prophylaxis were significantly less likely to develop empyema (OR 0.47, 95% CI 0.25 to 0.86, p=0.01). The benefit was greater in patients with penetrating injuries (penetrating OR 0.25, 95% CI 0.10 to 0.59, p=0.002, vs blunt OR 0.25, 95% CI 0.06 to 1.12, p=0.07). Administration of antibiotic prophylaxis did not significantly affect pneumonia incidence or mortality. Discussion: In adult trauma patients who require TT insertion, we conditionally recommend antibiotic prophylaxis be given at the time of insertion to reduce incidence of empyema. PROSPERO registration number: CRD42018088759.

Incidence and Diagnostic Challenges of Bowel Ischemia after Continuous-flow Left Ventricular Assist Device Therapy.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

Underutilization of Acetaminophen in Older Adult Trauma Patients.

INTRODUCTION: Older adults are more vulnerable to opioid-associated morbidity. The purpose of this study was to determine the frequency and timing of acetaminophen and opioid use in the postoperative period. METHODS: Older adult trauma patients (≥65 years) with hip fractures requiring femur or hip fixation were reviewed (Premier Database 2008-2014). We examined rates of acetaminophen use on the day of surgery and prior to receipt of oral opioids. Mixed-effects linear regression models were used to examine the effects of an acetaminophen-first approach on opioid use the day prior to and on the day of discharge. RESULTS: Of the 192 768 patients, 81.6% were Caucasian; 74.0% were female; and the mean age was 82.0 years [± 7.0]. Only 16.8% (32 291) of patients received acetaminophen prior to being prescribed opioids. 27.4% (52 779) received an acetaminophen-opioid combination, and 9.2% (17 730) received opioids without acetaminophen first. Acetaminophen first was associated with reduced opioid use on the day prior to and on the day of discharge (3.52 parenteral morphine equivalent doses (PMEs) less [95% CI: 3.33, 3.70]; P < .0001). A statistically but not clinically significant reduction in length of stay was observed in the acetaminophen-first group. CONCLUSION: Nearly 37% of older adult patients did not receive acetaminophen as first-line analgesia after hip surgery. Multimodal analgesia, including non-opioid medications as first-line, should be encouraged.

Bovine versus porcine acellular dermal matrix for abdominal wall herniorrhaphy or bridging.

BACKGROUND: The management of complicated ventral hernias (CVH), namely ventral hernias in actively or recently infected/contaminated operative fields, and open abdomens in which the native fascia cannot be primarily reapproximated, pose a surgical challenge. Fetal Bovine and Porcine Acellular Dermal Matrix (BADM and PADM) biologic meshes are being increasingly used in these scenarios. A comparison, however, of clinically relevant outcomes between the two is lacking. With this investigation, we aim to review and compare clinically relevant outcomes in patients that underwent abdominal wall herniorrhaphy with either BADM or PADM at a tertiary urban academic institution over a 5-year period. METHODS: Patients who had a BADM or PADM implanted during CVH over a 5-year period at a tertiary urban academic hospital were identified. Baseline clinical and hernia characteristics, as well as postoperative outcomes were compared after a retrospective chart review. Phone interviews were also conducted to assess for recurrence, followed by in-person visits as indicated. Cox Proportional Hazard regression was fitted to identify risk factors for recurrence. RESULTS: Of the 140 patients who underwent biologic mesh implantation for CVH, 109 were for ventral hernia repair and 31 for open abdomen bridging. Mean age was 52.7 ± 14.2 and males constituted 57.9% of our sample, while 25.1% had undergone > 5 prior abdominal operations. Thirty percent were active smokers, and another 30% required emergency surgery. Only immunosuppression was a risk factor for recurrence [HR 13.3 (1.04-169.2), p = 0.047] on Cox Proportional Hazard regression, while mesh selection had no effect. CONCLUSIONS: Both BADM and PADM meshes perform well in CVH, with satisfactory recurrence rates, only slightly higher compared to traditional synthetic mesh repairs.

Revision of the AAST grading scale for acute cholecystitis with comparison to physiologic measures of severity.

BACKGROUND: Grading systems for acute cholecystitis are essential to compare outcomes, improve quality, and advance research. The American Association for the Surgery of Trauma (AAST) grading system for acute cholecystitis was only moderately discriminant when predicting multiple outcomes and underperformed the Tokyo guidelines and Parkland grade. We hypothesized that through additional expert consensus, the predictive capacity of the AAST anatomic grading system could be improved. METHODS: A modified Delphi approach was used to revise the AAST grading system. Changes were made to improve distribution of patients across grades, and additional key clinical variables were introduced. The revised version was assessed using prospectively collected data from an AAST multicenter study. Patient distribution across grades was assessed, and the revised grading system was evaluated based on predictive capacity using area under receiver operating characteristic curves for conversion from laparoscopic to an open procedure, use of a surgical "bail-out" procedure, bile leak, major complications, and discharge home. A preoperative AAST grade was defined based on preoperative, clinical, and radiologic data, and the Parkland grade was also substituted for the operative component of the AAST grade. RESULTS: Using prospectively collected data on 861 patients with acute cholecystitis the revised version of the AAST grade has an improved distribution across all grades, both the overall grade and across each subscale. A higher AAST grade predicted each of the outcomes assessed (all p ≤ 0.01). The revised AAST grade outperformed the original AAST grade for predicting operative outcomes and discharge disposition. Despite this improvement, the AAST grade did not outperform the Parkland grade or the Emergency Surgery Score. CONCLUSION: The revised AAST grade and the preoperative AAST grade demonstrated improved discrimination; however, a purely anatomic grade based on chart review is unlikely to predict outcomes without addition of physiologic variables. Follow-up validation will be necessary. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.

Acute Respiratory Distress Syndrome (ARDS) after trauma: Improving incidence, but increasing mortality.

PURPOSE: Acute Respiratory Distress Syndrome (ARDS) is an infrequent, yet morbid inflammatory complication in injury victims. With the current project we sought to estimate trends in incidence, determine outcomes, and identify risk factors for ARDS and related mortality. MATERIALS & METHODS: The national Trauma Quality Improvement Program dataset (2010-2014) was queried. Demographics, injury characteristics and outcomes were compared between patients who developed ARDS and those who did not. Logistic regression models were fitted for the development of ARDS and mortality respectively, adjusting for relevant confounders. RESULTS: In the studied 808,195 TQIP patients, incidence of ARDS decreased over the study years (3-1.1%, p < 0.001), but related mortality increased (18.-21%, p = 0.001). ARDS patients spent an additional 14.7 ± 10.3 days in the hospital, 9.7 ± 7.9 in the ICU, and 6.6 ± 9.4 on mechanical ventilation (all p < 0.001). Older age, male gender, African American race increased risk for ARDS. Age, male gender, lower GCS and higher ISS also increased mortality risk among ARDS patients. Several pre-existing comorbidities including chronic alcohol use, diabetes, smoking, and respiratory disease also increased risk. CONCLUSION: Although the incidence of ARDS after trauma appears to be declining, mortality is on the rise.

Massive Transfusion Protocol Predictive Modeling in the Modern Electronic Medical Record.

Objectives: Integrate a predictive model for massive transfusion protocol (MTP) activation and delivery in the electronic medical record (EMR) using prospectively gathered data; externally validate the model and assess the accuracy and precision of the model over time. Background: The Emory model for predicting MTP using only four input variables was chosen to be integrated into our hospital's EMR to provide a real time clinical decision support tool. The continuous variable output allows for periodic re-calibration of the model to optimize sensitivity and specificity. Methods: Prospectively collected data from level 1 and 2 trauma activations were used to input heart rate, systolic blood pressure, base excess (BE) and mechanism of injury into the EMR-integrated model for predicting MTP activation and delivery. MTP delivery was defined as: 6 units of packed red blood cells/6 hours (MTP1) or 10 units in 24 hours (MTP2). The probability of MTP was reported in the EMR. ROC and PR curves were constructed at 6, 12, and 20 months to assess the adequacy of the model. Results: Data from 1162 patients were included. Areas under ROC for MTP activation, MTP1 and MTP2 delivery at 6, 12, and 20 months were 0.800, 0.821, and 0.831; 0.796, 0.861, and 0.879; and 0.809, 0.875, and 0.905 (all P < 0.001). The areas under the PR curves also improved, reaching values at 20 months of 0.371, 0.339, and 0.355 for MTP activation, MTP1 delivery, and MTP2 delivery. Conclusions: A predictive model for MTP activation and delivery was integrated into our EMR using prospectively collected data to externally validate the model. The model's performance improved over time. The ability to choose the cut-points of the ROC and PR curves due to the continuous variable output of probability of MTP allows one to optimize sensitivity or specificity.

Evaluation of malnutrition via modified GLIM criteria for in patients undergoing emergent gastrointestinal surgery.

BACKGROUND: Malnutrition remains a critical public health issue in the US, particularly in surgery where perioperative malnutrition is commonly underdiagnosed and undertreated. In 2016, the Global Leadership Initiative on Malnutrition (GLIM) proposed a set of consensus criteria for the diagnosis of malnutrition. Our project aims to assess the post-operative outcomes of patients meeting a modified GLIM-defined (mGLIM) malnutrition criteria undergoing emergent gastrointestinal surgery (EGS) in the NSQIP database. Current GLIM-criteria were modified with addition of admission albumin (a NSQIP-defined malnutrition variable). METHODS: Adapting NSQIP data, mGLIM criteria are (1) BMI of ≤20 for age ≤ 70 and BMI ≤22 for age ≥ 71, (2) weight loss > 10% within the past 6 months, (3) admission albumin ≤ 3.5, and (4) emergent bowel surgery as etiologic criteria of acute disease/injury. All patients undergoing emergent small bowel, colon, and rectal procedures were extracted from the NSQIP database and included in the study. Multivariate linear and logistic regression models controlling for relevant covariates were developed to evaluate mGLIM criteria on length of stay (LOS), mortality, and overall complication rates. RESULTS: We included 31,029 patients who underwent emergent bowel surgeries from years 2011-2016. Demographically, 53.6% (n = 16,622) were female, 13.0% (n = 4023) were African American, and 78.3% (n = 24,292) were Caucasian. Case composition included 71.5% colon operations, 28.0% small bowel, and 0.5% rectal cases. Overall, 1.7% (n = 517) had data necessary to qualify as malnourished as per mGLIM. Controlling for covariates, multivariate linear and logistic regression analyses show that these patients have significantly higher mortality for both colon (p < 0.001, CI 1.55 | 2.61) and small bowel (p = 0.022, CI 1.08 | 2.67) procedures, longer LOS for colon (p < 0.001, CI 1.93 | 4.33) operations, and higher post-operative complications for both colon (p < 0.001, CI 1.61 | 2.62) and small bowel (p < 0.001, CI 1.57 | 3.37) cases. CONCLUSION: This analysis shows that mGLIM criteria malnutrition is associated with poor clinical outcomes following EGS affecting LOS and mortality. Our data indicates the new mGLIM criteria can be a powerful and simple predictive score for malnutrition that can be used to predict malnutrition-related risk of poor outcomes after EGS.