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 the 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.

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.

Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A.

INTRODUCTION: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation. AIM: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec. METHODS: To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time-course data for participants in GENEr8-1. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4 weeks after valoctocogene roxaparvovec infusion. RESULTS: Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4 weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8-1 participants are presented to illustrate how decisions may vary among individuals. CONCLUSION: Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy-derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec.

Racial and ethnic demographics in malnutrition related deaths.

BACKGROUND AND AIMS: Currently, 40 million Americans are food insecure. They are forced to skip meals and buy non-nutritious food, leading to health disparities for those of low socioeconomic status. This study aims to investigate relationships between malnutrition deaths and sociodemographic groups. METHODS: This cross-sectional study from 2009 to 2018 used aggregate data from the CDC Wide-ranging Online Data for Epidemiologic Research (CDC Wonder). Patients with known race, gender, and Hispanic origin age ≥18 who died from malnutrition (E40-E46) were included. Place of death was grouped into home, inpatient medical facility, hospice facility, nursing facility/long-term care, other (including outpatient, ED, and DOA), and unknown. Crude rates of malnutrition deaths per 100,000 persons for race, gender, and Hispanic origin were calculated using US census estimates. Gross proportions of total deaths were calculated for each place of death. RESULTS: Between 2009 and 2018, there were 46,517 malnutrition deaths in the US. Death rates for Black (1.8) and White Americans (2) were twice as high compared to Native Americans (1.1) and Asians or Pacific Islanders (0.7). Death rates among females (2.3) were higher than males (1.5). Death rates among non-Hispanics (2.1) were twice as high compared to Hispanics (0.7). Most people who died of malnutrition died in hospitals (37 %). CONCLUSION: Malnutrition deaths occur at greater rates among White, Black, non-Hispanic Americans, and females. Despite reported disparities in food access, Black and White Americans have similar malnutrition mortality rates, raising concerns that malnutrition is under-diagnosed among Black patients. Given the existing nutrition literature, this finding requires further investigation.

Systematic Literature Review of Health-Related Quality-of-Life Measures for Caregivers of Older Adult Trauma Patients.

INTRODUCTION: As the older adult population increases, hospitals treat more older adults with injuries. After leaving, these patients suffer from decreased mobility and independence, relying on care from others. Family members often assume this responsibility, mostly informally and unpaid. Caregivers of other older adult populations have increased stress and decreased caregiver-related quality of life (CRQoL). Validated CRQoL measures are essential to capture their unique experiences. Our objective was to review existing CRQoL measures and their validity in caregivers of older adult trauma patients. METHODS: A professional librarian searched published literature from the inception of databases through August 12, 2022 in MEDLINE (via PubMed), Embase (via Elsevier), and CINAHL Complete (via EBSCO). We identified 1063 unique studies of CRQoL in caregivers for adults with injury and performed a systematic review following COnsensus-based Standards for the selection of health Measurement Instruments guidelines for CRQoL measures. RESULTS: From the 66 studies included, we identified 54 health-related quality-of-life measures and 60 domains capturing caregiver-centered concerns. The majority (83%) of measures included six or fewer CRQoL content domains. Six measures were used in caregivers of older adults with single-system injuries. There were no validated CRQoL measures among caregivers of older adult trauma patients with multisystem injuries. CONCLUSIONS: While many measures exist to assess healthcare-related quality of life, few, if any, adequately assess concerns among caregivers of older adult trauma patients. We found that CRQoL domains, including mental health, emotional health, social functioning, and relationships, are most commonly assessed among caregivers. Future measures should focus on reliability and validity in this specific population to guide interventions.

Outcomes by time-to-OR for penetrating abdominal trauma patients.

INTRODUCTION: Time-To-OR is a critical process measure for trauma performance. However, this measure has not consistently demonstrated improvement in outcome. STUDY DESIGN: Using TQIP, we identified facilities by 75th percentile time-to-OR to categorize slow, average, and fast hospitals. Using a GEE model, we calculated odds of mortality for all penetrating abdominal trauma patients, firearm injuries only, and patients with major complication by facility speed. We additionally estimated odds of mortality at the patient level. RESULTS: Odds of mortality for patients at slow facilities was 1.095; 95% CI: 0.746, 1.608; p = 0.64 compared to average. Fast facility OR = 0.941; 95% CI: 0.780, 1.133; p = 0.52. At the patient-level each additional minute of time-to-OR was associated with 1.5% decreased odds of in-hospital mortality (OR 0.985; 95% CI:0.981, 0.989; p < 0.001). For firearm-only patients, facility speed was not associated with odds of in-hospital mortality (p-value = 0.61). Person-level time-to-OR was associated with 1.8% decreased odds of in-hospital mortality (OR 0.982; 95% CI: 0.977, 0.987; p < 0.001) with each additional minute of time-to-OR. Similarly, failure-to-rescue analysis showed no difference in in-hospital mortality at the patient level (p = 0.62) and 0.4% decreased odds of in-hospital mortality with each additional minute of time-to-OR at the patient level (OR 0.996; 95% CI: 0.993, 0.999; p = 0.004). CONCLUSION: Despite the use of time-to-OR as a metric of trauma performance, there is little evidence for improvement in mortality or complication rate with improved time-to-OR at the facility or patient level. Performance metrics for trauma should be developed that more appropriately approximate patient outcome.

Efficacy of BETTER transitional care intervention for diverse patients with traumatic brain injury and their families: Study protocol of a randomized controlled trial.

OBJECTIVE: The purpose of this study is to examine the efficacy of BETTER (Brain Injury, Education, Training, and Therapy to Enhance Recovery) vs. usual transitional care management among diverse adults with traumatic brain injury (TBI) discharged home from acute hospital care and families. METHODS: This will be a single-site, two-arm, randomized controlled trial (N = 436 people, 218 patient/family dyads, 109 dyads per arm) of BETTER, a culturally- and linguistically-tailored, patient- and family-centered, TBI transitional care intervention for adult patients with TBI and families. Skilled clinical interventionists will follow a manualized protocol to address patient/family needs. The interventionists will co-establish goals with participants; coordinate post-hospital care, services, and resources; and provide patient/family education and training on self- and family-management and coping skills for 16 weeks following hospital discharge. English- and Spanish-speaking adult patients with mild-to-severe TBI who are discharged directly home from the hospital without inpatient rehabilitation or transfer to other settings (community discharge) and associated family caregivers are eligible and will be randomized to treatment or usual transitional care management. We will use intention-to-treat analysis to determine if patients receiving BETTER have a higher quality of life (primary outcome, SF-36) at 16-weeks post-hospital discharge than those receiving usual transitional care management. We will conduct a descriptive, qualitative study with 45 dyads randomized to BETTER, using semi-structured interviews, to capture perspectives on barriers and facilitators to participation. Data will be analyzed using conventional content analysis. Finally, we will conduct a cost/budget impact analysis, evaluating differences in intervention costs and healthcare costs by arm. DISCUSSION: Findings will guide our team in designing a future, multi-site trial to disseminate and implement BETTER into clinical practice to enhance the standard of care for adults with TBI and families. The new knowledge generated will drive advancements in health equity among diverse adults with TBI and families. TRIAL REGISTRATION: NCT05929833.

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.

Factors Associated with Discharge to Skilled Nursing Facility Following Gunshot Wounds.

INTRODUCTION: Firearm injury is a public health crisis. Most victims are minorities in underserved neighborhoods. Measuring firearm injury by mortality underestimates its impact, as most victims survive to discharge. This study was done to determine if race and insurance status are associated with discharge disposition for gunshot wound (GSW)-related trauma. METHODS: Using the 2019 Trauma Quality Improvement Program database, we identified GSW patients with Abbreviated Injury Scale (AIS) = 1-3. Exclusion criteria included patients who died in hospital and routine home discharge. We compared discharge patterns of patients based on demographics (age, gender, race, ethnicity, payor, AIS, hospital designation, and length of stay [LOS]) and injury severity. Multivariable logistic regression models identified factors associated with discharge disposition. RESULTS: Our sample included 2437 patients with GSWs. On univariable analysis, Black patients were more likely to discharge to home with home health (64.1% Black versus 34.7% White; P < 0.001). White patients were more likely to discharge to skilled nursing facility (SNF) (51.4% White versus 44.6% Black; P < 0.001). Controlling for age, race, Latin ethnicity, primary payor, LOS, AIS severity, and injury severity score factors independently associated with discharge to SNF included age (0.0462, P < 0.001), Medicaid (1.136, P < 0.0003), Medicare (1.452, P < 0.001), and LOS (0.03745, P < 0.001). CONCLUSIONS: Postacute care following traumatic injuries is essential to recovery. Black GSW victims are more likely to be discharged to home health than White patients, who are more likely to be discharged to SNF. Targeted programs to reduce barriers to appropriate aftercare are necessary to eliminate this bias and improve the care of underserved populations.

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.

The BETTER Traumatic Brain Injury Transitional Care Intervention: A Feasibility Study.

This study aimed to investigate the feasibility, acceptability, and clinical outcome measures of BETTER (Brain Injury Education, Training, and Therapy to Enhance Recovery), a culturally tailored traumatic brain injury (TBI) transitional care intervention, among diverse younger adult patients with TBI (age 18-64) and their caregivers. Trained clinical interventionists addressed patient/family needs; established goals; coordinated post-hospital care and resources; and provided patient/family training on self- and family-management coping skills. Fifteen dyads enrolled (N = 31, 15 patients, 16 caregivers). All completed baseline data; 74.2% (n = 23; 10 patients, 13 caregivers) completed 8-week data; 83.8% (n = 26; 13 each) completed 16-week data. Approximately 38% (n = 12, 3 patients, 9 caregivers) completed acceptability data, showing positive experiences (mean = 9.25, range 0-10; SD = 2.01). Overall and mental quality of life (QOL) scores did not differ over time but physical QOL scores did improve over time (baseline: 30.3, 8 weeks: 46.5, 16 weeks: 61.6; p = 0.0056), which was considered to be a suitable outcome measure for a future trial. BETTER is a promising intervention with implications to improve TBI care standards. Research is needed to determine efficacy in a randomized trial.

A National Comparison of Volume and Acuity for Adult and Pediatric Trauma: A Trauma Quality Improvement Program Cohort Study.

INTRODUCTION: Most injured children receive trauma care outside of a pediatric trauma center. Differences in physiology, dosing, and injury pattern limit extrapolation of adult trauma principles to pediatrics. We compare US trauma center experience with pediatric and adult trauma resuscitation. MATERIALS AND METHODS: We queried the 2019 Trauma Quality Improvement Program to describe the experience of US trauma centers with pediatric (<15 y) and adult trauma. We quantified blunt, penetrating, burn, and unspecified traumas and compared minor, moderate, severe, and critical traumas (ISS 1-8 Minor, ISS 9-14 Moderate, ISS 15-24 Severe, ISS 25+ Critical). We estimated center-level volumes for adults and children. Institutional identifiers were generated based on unique center specific factors including hospital teaching status, hospital type, verification level, pediatric verification level, state designation, state pediatric designation, and bed size. RESULTS: A total of 755,420 adult and 76,449 pediatric patients were treated for traumatic injuries. There were 21 times as many critical or major injuries in adults compared to children, 17 times more moderate injuries, and 6 times more minor injuries. Children and adults presented with similar rates of blunt trauma, but penetrating injuries were more common in adults and burn injuries were more common in children. Comparing center-level data, adult trauma exceeded pediatric for every severity and mechanism. CONCLUSIONS: There is relatively limited exposure to high-acuity pediatric trauma at US centers. Investigation into pediatric trauma resuscitation education and simulation may promote pediatric readiness and lead to improved outcomes.

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.