Effects of an Intervention to Improve Evidence-Based Care for People With Diabetes and Cardiovascular Disease Across Sex, Race, and Ethnicity Subgroups: Insights From the COORDINATE-Diabetes Trial.

BACKGROUND: Results from the COORDINATE-Diabetes trial (Coordinating Cardiology Clinics Randomized Trial of Interventions to Improve Outcomes - Diabetes) demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity. METHODS: COORDINATE-Diabetes, a cluster randomized trial, recruited participants from 43 US cardiology clinics (20 randomized to intervention and 23 randomized to usual care). The primary outcome was the proportion of participants prescribed all 3 groups of evidence-based therapy (high-intensity statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide 1 receptor agonist) at last trial assessment (6 to 12 months). In this prespecified analysis, mixed-effects logistic regression models were used to assess the outcome by self-reported sex, race, and ethnicity in the intervention and usual care groups, with adjustment for baseline characteristics, medications, comorbidities, and site location. RESULTS: Among 1045 participants with type 2 diabetes and atherosclerotic cardiovascular disease, the median age was 70 years, 32% were female, 16% were Black, and 9% were Hispanic. At the last trial assessment, there was an absolute increase in the proportion of participants prescribed all 3 groups of evidence-based therapy in women (36% versus 15%), Black participants (41% versus 18%), and Hispanic participants (46% versus 18%) with the intervention compared with usual care, with consistent benefit across sex (male versus female; Pinteraction=0.44), race (Black versus White; Pinteraction=0.59), and ethnicity (Hispanic versus Non-Hispanic; Pinteraction= 0.78). CONCLUSIONS: The COORDINATE-Diabetes intervention successfully improved delivery of evidence-based care, regardless of sex, race, or ethnicity. Widespread dissemination of this intervention could improve equitable health care quality, particularly among women and minority communities who are frequently underrepresented in clinical trials. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03936660.

Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future.

Among newer classes of drugs for type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are incretin-based agents that lower both blood sugar levels and promote weight loss. They do so by activating pancreatic GLP-1 receptors (GLP-1R) to promote glucose-dependent insulin release and inhibit glucagon secretion. They also act on receptors in the brain and gastrointestinal tract to suppress appetite, slow gastric emptying, and delay glucose absorption. Phase 3 clinical trials have shown that GLP-1 RAs improve cardiovascular outcomes in the setting of T2DM or overweight/obesity in people who have, or are at high risk of having atherosclerotic cardiovascular disease. This is largely driven by reductions in ischemic events, although emerging evidence also supports benefits in other cardiovascular conditions, such as heart failure with preserved ejection fraction. The success of GLP-1 RAs has also seen the evolution of other incretin therapies. Tirzepatide has emerged as a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, with more striking effects on glycemic control and weight reduction than those achieved by isolated GLP-1R agonism alone. This consists of lowering glycated hemoglobin levels by more than 2% and weight loss exceeding 15% from baseline. Here, we review the pharmacological properties of GLP-1 RAs and tirzepatide and discuss their clinical effectiveness for T2DM and overweight/obesity, including their ability to reduce adverse cardiovascular outcomes. We also delve into the mechanistic basis for these cardioprotective effects and consider the next steps in implementing existing and future incretin-based therapies for the broader management of cardiometabolic disease.

Fusogenic vesicular stomatitis virus combined with natural killer T cell immunotherapy controls metastatic breast cancer.

BACKGROUND: Metastatic breast cancer is a leading cause of cancer death in woman. Current treatment options are often associated with adverse side effects and poor outcomes, demonstrating the need for effective new treatments. Immunotherapies can provide durable outcomes in many cancers; however, limited success has been achieved in metastatic triple negative breast cancer. We tested whether combining different immunotherapies can target metastatic triple negative breast cancer in pre-clinical models. METHODS: Using primary and metastatic 4T1 triple negative mammary carcinoma models, we examined the therapeutic effects of oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express reovirus-derived fusion associated small transmembrane proteins p14 (VSV-p14) or p15 (VSV-p15). These viruses were delivered alone or in combination with natural killer T (NKT) cell activation therapy mediated by adoptive transfer of α-galactosylceramide-loaded dendritic cells. RESULTS: Treatment of primary 4T1 tumors with VSV-p14 or VSV-p15 alone increased immunogenic tumor cell death, attenuated tumor growth, and enhanced immune cell infiltration and activation compared to control oncolytic virus (VSV-GFP) treatments and untreated mice. When combined with NKT cell activation therapy, oncolytic VSV-p14 and VSV-p15 reduced metastatic lung burden to undetectable levels in all mice and generated immune memory as evidenced by enhanced in vitro recall responses (tumor killing and cytokine production) and impaired tumor growth upon rechallenge. CONCLUSION: Combining NKT cell immunotherapy with enhanced oncolytic virotherapy increased anti-tumor immune targeting of lung metastasis and presents a promising treatment strategy for metastatic breast cancer.

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant.

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.

Less Is More: Dissecting Trauma Centers by Procedural Volume.

OBJECTIVE: This study aims to examine the relationship between procedural volume and annual trauma volume (ATV) of ACS Level I trauma centers (TC). BACKGROUND: Although ATV is a hard criterion for TC verification, importance of procedural interventions as a potential quality indicator is understudied. METHODS: Patients managed at ACS level I TCs were identified from ACS-TQIP 2017-2021. TCs were identified using facility keys and stratified into quartiles based on ATV into low, low-medium, medium-high, and high volume. TCs were also stratified into tertiles [low (LV), medium (MV), high (HV)] based on procedural volume by assessing annual number of laparotomies, thoracotomies, craniotomies/craniectomies, angioembolizations, vascular repairs, and long bone fixations performed at each center. The Cohen κ statistic was used to assess concordance between ATV and procedural volume. RESULTS: A total of 182 Level I TCs were identified: 76 low, 47 low-medium, 35 high-medium, and 24 high volume. Long bone fixation, laparotomy, and craniotomy/craniectomy were the most performed procedures with a median of 65, 59, and 46 cases/center/year, respectively. Overall, 31% of HV laparotomy centers, 31% of HV thoracotomy centers, 22% of HV craniotomy/craniectomy centers, 22% of HV vascular repair centers, 32% of HV long bone fixation centers, and 33% of HV angioembolization centers contributed to the overall number of low-medium and low-volume TCs. The Cohen κ statistic demonstrated poor concordance between ATV and procedural volumes for all procedures (overall procedural volume-κ=0.378, laparotomy-κ=0.270, thoracotomy-κ=0.202, craniotomy/craniectomy-κ=0.394, vascular repair-κ=0.298, long bone fixation-κ=0.277, angioembolization-κ=0.286). CONCLUSIONS: ATV does not reflect the procedural interventions performed. Combination of procedural and ATV may provide a more accurate picture of the clinical experience at any given TC. LEVEL OF EVIDENCE: Level III.

Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN.

BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. CONCLUSION: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders.

The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.

How Will Our Practice Change After the CLEAR Outcomes Trial?

PURPOSE OF REVIEW: Bempedoic acid is a novel therapeutic agent that is designed to reduce levels of low-density lipoprotein cholesterol (LDL-C). The purpose of this review is to provide the background for development of bempedoic acid, findings from clinical trials and to discuss clinical implications. RECENT FINDINGS: Bempedoic acid inhibits ATP citrate lyase within the liver and reduces cholesterol synthesis, with the potential to avoid muscle symptoms experienced by patients treated with statins. Early clinical studies demonstrated that administration of bempedoic acid resulted in lowering of LDL-C by 20-30% as monotherapy and by 40-50% when combined with ezetimibe, in addition to lowering of high sensitivity C-reactive protein by 20-30%. The CLEAR Outcomes trial of high cardiovascular risk patients, with elevated LDL-C levels and either unable or unwilling to take statins demonstrated that bempedoic acid reduced the rate of major adverse cardiovascular events. A greater incidence of elevation of hepatic transaminase and creatinine, gout, and cholelithiasis were consistently observed in bempedoic acid-treated patients. Bempedoic acid presents an additional therapeutic option to achieve more effective lowering of LDL-C levels and reduction in cardiovascular risk.

What Is Going on in Our Schools? Review of Injuries Among School Children Across the United States.

INTRODUCTION: Children spend most of their time at school and participate in many activities that have the potential for causing injury. This study aims to describe the nationwide epidemiology of pediatric trauma sustained in school settings in the United States. METHODS: In the 3-y analysis of 2017-2019 American College of Surgeons-Trauma Quality Program, all pediatric trauma patients (≤18 y) injured in a school setting were included and stratified based on place of injury, into elementary, middle, and high school (HS) groups. Descriptive statistics and multivariable logistic regression analysis were performed to identify the independent predictors of intentional injuries. RESULTS: 23,215 pediatric patients were identified, of which 15,264 patients were injured at elementary (57.6%), middle (17.5%), and high (25%) schools. The mean age was 9.5 y, 66.9% were male, 63.9% were white, the median injury severity score was 2 [1-4], and 95.6% had a blunt injury. Elementary school students were more likely to sustain falls (85%) and humerus fractures (43%) whereas HS students were more likely to be injured by assaults (17%). Overall, 7% of the students sustained intentional injuries. On multivariable logistic regression, male gender (odds ratio [OR] 1.54), Black race (OR 2.94), American Indian race (OR 1.88), Hispanic ethnicity (OR 1.77), positive drug screen (OR 4.9), middle (OR 5.2), and HSs (OR 10.6) were identified as independent predictors of intentional injury (all P < 0.01). CONCLUSIONS: Injury patterns vary across elementary, middle, and HSs. Racial factors appear to influence intentional injuries along with substance abuse. Further studies to understand these risk factors and efforts to reduce school injuries are warranted to provide a safe learning environment for children.

Diagnostic Laparoscopy in Trauma Patients: Do We Need to Open and See if We Can See Without Opening?

BACKGROUND: Diagnostic laparoscopy (DL) has been advocated to reduce the incidence of nontherapeutic laparotomies (NL) among stable trauma patients. This study aimed to compare the outcomes of hemodynamically stable trauma patients undergoing DL versus NL. METHODS: This is a retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database over 4 y (2017-2020). Hemodynamically stable (systolic blood pressure >90 & heart rate < 120) adult (≥18 y) trauma patients undergoing DL or NL were included. Patients were stratified into DL and NL and substratified based on the mechanism of injury (blunt versus penetrating) and compared. RESULTS: Over 4 y, 3801 patients were identified, of which, 997 (26.2%) underwent DL. Overall, 25.6% sustained blunt injuries. The mean (SD) age was 39 (16) and 79.5% were male. The median injury severity score and abdominal abbreviated injury scale were 4 [4-9] and 1 [1-2], with no difference among study groups (P ≥ 0.05). The overall mortality and major complication rates were 2.8% and 13.2%, respectively. After controlling for potential confounding factors, DL was independently associated with lower odds of mortality (adjusted odds ratio: 0.10, 95% CI [0.04-0.29], P < 0.001) and major complications (adjusted odds ratio: 0.38, 95% CI [0.29-0.50], P < 0.001) and shorter hospital length of stay (ß: -1.22, 95% CI [-1.78 to -0.67], P < 0.001). The trends toward improved outcomes in the DL group remained the same in the subanalysis of patients with penetrating and blunt injuries. CONCLUSIONS: With advances in minimally invasive surgery, unnecessary exploratory laparotomy can be avoided in many trauma patients. Our study shows that hemodynamically stable patients undergoing DL had superior outcomes compared to those with NL.

Failure to Rescue in Geriatric Ground-Level Falls: The Role of Frailty on Not-So-Minor Injuries.

INTRODUCTION: The measure of mortality following a major complication (failure to rescue [FTR]) provides a quantifiable assessment of the level of care provided by trauma centers. However, there is a lack of data on the effects of patient-related factors on FTR incidence. The aim of this study was to identify the role of frailty on FTR incidence among geriatric trauma patients with ground-level falls (GLFs). METHODS: This is a retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database (2017-2020). All geriatric (aged ≥ 65 ys) trauma patients with GLFs admitted to a level I trauma center were included. Transferred patients, those with severe head injuries (head abbreviated injury scale ≥ 3), and those who died within 24 h of admission or whose length of stay was ≤1 d were excluded. FTR was defined as death following a major complication (cardiac arrest, myocardial infarction, sepsis, acute respiratory distress syndrome, unplanned intubation, acute renal failure, cerebrovascular accident, ventilator-associated pneumonia, or pulmonary embolism). Patients were stratified into frail (F) and nonfrail (NF) based on the 11-Factor Modified Frailty Index. Multivariable regression analyses were performed to identify the independent effect of frailty on the incidence of FTR. RESULTS: Over 4 ys, 34,100 geriatric patients with GLFs were identified, of whom 9140 (26.8%) were F. The mean (standard deviation) age was 78 (7) years and 65% were female. The median injury severity score was 9 (5-10) with no difference among F and NF groups (P = 0.266). Overall, F patients were more likely to develop major complications (F: 3.6% versus NF: 2%, P < 0.001) and experience FTR (F: 1.8%% versus NF: 0.6%, P < 0.001). Moreover, among patients with major complications, F patients were more likely to die (F: 47% versus NF: 27%, P < 0.001). On multivariable regression analysis, frailty was identified as an independent predictor of major complications (adjusted odds ratio: 1.98, 95% confidence interval [1.70-2.29], P < 0.001) and FTR (adjusted odds ratio: 2.26, 95% confidence interval [1.68-3.05], P < 0.001). CONCLUSIONS: Among geriatric trauma patients with GLFs, frailty increases the risk-adjusted odds of FTR by more than two times. One in every two F patients with a major complication does not survive to discharge. Future efforts should concentrate on improving patient-related and hospital-related factors to decrease the risk of FTR among these vulnerable populations.

The Role of Whole Blood Hemostatic Resuscitation in Bleeding Geriatric Trauma Patients.

INTRODUCTION: Whole blood (WB) has recently gained increased popularity as an adjunct to the resuscitation of hemorrhaging civilian trauma patients. We aimed to assess the nationwide outcomes of using WB as an adjunct to component therapy (CT) versus CT alone in resuscitating geriatric trauma patients. METHODS: We performed a 5-y (2017-2021) retrospective analysis of the Trauma Quality Improvement Program. We included geriatric (age, ≥65 y) trauma patients presenting with hemorrhagic shock (shock index >1) and requiring at least 4 units of packed red blood cells in 4 h. Patients with severe head injuries (head Abbreviated Injury Scale ≥3) and transferred patients were excluded. Patients were stratified into WB-CT versus CT only. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications. Multivariable regression analysis was performed, adjusting for potential confounding factors. RESULTS: A total of 1194 patients were identified, of which 141 (12%) received WB. The mean ± standard deviation age was 74 ± 7 y, 67.5% were male, and 83.4% had penetrating injuries. The median [interquartile range] Injury Severity Score was 19 [13-29], with no difference among study groups (P = 0.059). Overall, 6-h, 24-h, and in-hospital mortality were 16%, 23.1%, and 43.6%, respectively. On multivariable regression analysis, WB was independently associated with reduced 24-h (odds ratio, 0.62 [0.41-0.94]; P = 0.024), and in-hospital mortality (odds ratio, 0.60 [0.40-0.90]; P = 0.013), but not with major complications (odds ratio, 0.78 [0.53-1.15]; P = 0.207). CONCLUSIONS: Transfusion of WB as an adjunct to CT is associated with improved early and overall mortality in geriatric trauma patients presenting with severe hemorrhage. The findings from this study are clinically important, as this is an essential first step in prioritizing the selection of WB resuscitation for geriatric trauma patients presenting with hemorrhagic shock.

Trauma Laparotomy for the Cirrhotic Patient: An Outcome-Based Analysis.

INTRODUCTION: There is a lack of large-scale data on outcomes of cirrhotic patients undergoing trauma laparotomy. We aimed to compare outcomes of cirrhotic versus noncirrhotic trauma patients undergoing laparotomy. METHODS: We analyzed 2018 American College of Surgeons Trauma Quality Improvement Program. We included blunt trauma patients (≥18 y) who underwent a laparotomy. Patients who were transferred, dead on arrival, or had penetrating injuries were excluded. Patients were matched in a 1:2 ratio (cirrhotic and noncirrhotic). Outcomes included mortality, complications, failure to rescue, transfusion requirements, and hospital and intensive care unit (ICU) lengths of stay. Multivariable backward stepwise regression analysis was performed. RESULTS: Four hundred and seventy-one patients (cirrhotic, 157; noncirrhotic, 314) were matched. Mean age was 57 ± 15 y, 78% were male, and median injury severity score was 24. Cirrhotic patients had higher rates of mortality (60% versus 30%, P value <0.001), complications (49% versus 37%; P value = 0.01), failure to rescue (66% versus 36%, P value<0.001), and pRBC (units, median, 11 [7-18] versus 7 [4-11], P value <0.001) transfusion requirements. There were no significant differences in hospital and intensive care unit (ICU) lengths of stay (P value ≥0.05). On multivariate analysis, increasing age (adjusted odds ratio [aOR] 1.02, P value <0.001), Glasgow Coma Scale score ≤8 at presentation (aOR 3.3, P value <0.001), and total splenectomy (aOR 5.7, P value <0.001) were associated with higher odds of mortality. Platelet transfusion was associated with lower odds of mortality (aOR 0.84, P value = 0.044). CONCLUSIONS: On a national scale, mortality following trauma laparotomy is twice as high for cirrhotic patients compared to noncirrhotic patients with higher rates of major complications and failure to rescue. Our finding of a protective effect of platelet transfusion may be explained by the platelet dysfunction associated with cirrhosis. Liver cirrhosis among trauma patients warrants heightened surveillance.

Should We Keep or Transfer Our Severely Injured Geriatric Patients to Higher Levels of Care?

INTRODUCTION: Interfacility transfer to higher levels of care is becoming increasingly common. This study aims to evaluate the association between transfer to higher levels of care and prolonged transfer times with outcomes of severely injured geriatric trauma patients compared to those who are managed definitively at lower-level trauma centers. METHODS: Severely injured (Injury Severity Score >15) geriatric (≥60 y) trauma patients in the 2017-2018 American College of Surgeons Trauma Quality Improvement Program database managing at an American College of Surgeons/State Level III trauma center or transferring to a level I or II trauma center were included. Outcome measures were 24-h and in-hospital mortality and major complications. RESULTS: Forty thousand seven hundred nineteen patients were identified. Mean age was 75 ± 8 y, 54% were male, 98% had a blunt mechanism of injury, and the median Injury Severity Score was 17 [16-21]. Median transfer time was 112 [79-154] min, and the most common transport mode was ground ambulance (82.3%). Transfer to higher levels of care within 90 min was associated with lower 24-h mortality (adjusted odds ratio [aOR]: 0.493, P < 0.001) and similar odds of in-hospital mortality as those managed at level III centers. However, every 30-min delay in transfer time beyond 90 min was progressively associated with increased odds of 24-h (aOR: 1.058, P < 0.001) and in-hospital (aOR: 1.114, P < 0.001) mortality and major complications (aOR: 1.127, P < 0.001). CONCLUSIONS: Every 30-min delay in interfacility transfer time beyond 90 min is associated with 6% and 11% higher risk-adjusted odds of 24-h and in-hospital mortality, respectively. Estimated interfacility transfer time should be considered while deciding about transferring severely injured geriatric trauma patients to a higher level of care.

From Procedure to Prognosis: The Association Between Obesity and Outcomes of Iliac Artery Injuries.

INTRODUCTION: The management of injuries to the iliac artery presents a challenging clinical scenario due to the impeded anatomical access. Obesity is a common comorbid condition known to affect the outcomes of trauma patients; however, there is a paucity of data on the association of obesity with the treatment and outcomes of iliac artery injuries. The aim of this study was to assess the association between body mass index (BMI) on the management and outcomes of patients with iliac artery injuries. METHODS: This is a retrospective analysis of the American College of Surgeons-Trauma Quality Improvement Program (2017-2020). All adult (aged ≥18 y) trauma patients with iliac artery injuries who underwent open or endovascular repair were included. Patients were divided based on BMI (normal: BMI <25 kg/m2, overweight: BMI ≥25-30 kg/m2, obese: BMI ≥30 kg/m2) and compared. Outcomes included rates of open and endovascular repair, in-hospital mortality, and complications. Multivariable regression analysis was performed for these outcomes. RESULTS: A total of 380 patients were identified who underwent repair (Open: 61%, Endovascular: 39%) for iliac artery injuries. The mean (standard deviation) age was 41 (19) y and 74% were male. There was no difference in the rates of open or endovascular repair among the BMI categories (P = 0.332). The median (interquartile range) injury severity score was 22 (9-29) with no difference among the BMI categories (P = 0.244). On univariate analysis, the rates of mortality and major complications were higher among obese patients compared to overweight and normal BMI groups (P < 0.05) (Table). On multivariable regression analysis, increasing BMI was not a predictor of open or endovascular repair of the iliac arteries; however, increasing BMI was independently associated with higher odds of major complications (adjusted odds ratio [aOR]: 1.09, 95% confidence interval [CI] [1.02-1.16], P = 0.007), acute kidney injury (aOR: 1.13, 95% CI [1.02-1.24], P = 0.015), acute respiratory distress syndrome (aOR: 1.18, 95% CI [1.01-1.38], P = 0.031), and mortality (aOR: 1.30, 95% CI [1.06-1.59], P = 0.009). CONCLUSIONS: Although BMI was not identified as a predictor of the type of repair for iliac artery injuries, increasing BMI was significantly associated with mortality, complications, and acute kidney injury in patients who undergo repair of the iliac arteries. Future research is warranted to identify the optimal management approach for obese patients to improve the outcomes.

The Synergy Factor: Trauma and Cancer.

INTRODUCTION: Trauma and cancer are the leading causes of death in the US. There is a paucity of data describing the impact of cancer on trauma patients. We aimed to determine the influence of cancer on outcomes of trauma patients. METHODS: In this retrospective analysis of American College of Surgeons-Trauma Quality Improvement Program 2019-2021, we included all adult trauma patients (≥18 y) and excluded patients with severe head injuries and nonmelanomatous skin cancers. Patients were stratified into cancer (C), and no cancer (No-C). Propensity score matching (1:3) was performed. Outcomes were complications and mortality. RESULTS: A matched cohort of 3236 patients (C, 809; No-C, 2427) was analyzed. The mean age was 70 y, 50.5% were males, and the median injury severity score was 8 (4-10). There were no differences in terms of receiving thromboprophylaxis (C 51%: No-C 50%, P = 0.516). Compared to No-C group, the C group had higher rates of deep vein thrombosis (C 1.1% versus No-C 0.3%, P = 0.004), but there was no difference in terms of overall complications. Patients in the C group had higher mortality (C 7.5% versus No-C 2.7%, P < 0.001). CONCLUSIONS: Trauma patients with cancer have nearly 4 times higher odds of deep vein thrombosis and 3 times higher odds of mortality. Developing pathways specific to cancer patients might be necessary to improve the outcomes of trauma patients with cancer.

Endovascular Versus Open Repair in Adolescent Patients With Difficult-to-Access Vascular Injuries.

INTRODUCTION: Management of subclavian artery injuries (SAI) and iliac artery injuries (IAI) in adolescent trauma patients poses a considerable challenge due to their complex anatomical locations. The aim of our study was to determine the association between the injury mechanism and type of repair with the outcomes of patients with traumatic SAI and IAI. METHODS: In this retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database2017-2020, adolescent (<18 y) patients with SAI and IAI undergoing either endovascular or open repair were included. Patients were stratified by mechanism (blunt versus penetrating) and type of repair (endovascular [E] versus open [O]) and compared. Outcomes measured were mortality and major complications. Multivariable logistic regression analyses were performed. RESULTS: Over 4 y, 170 pediatric patients were identified, of which 73 (43%) sustained an SAI and 97 (57%) had IAI. The mean age was 15 and 79% were male. Overall, 39% were managed endovascularly. Both groups had comparable median injury severity score (E: 23 versus O: 25, P = 0.278). For patients with blunt injury (n = 60), the type of repair was neither associated with major complications (E: 39% versus O: 33%, P = 0.694) nor mortality (E: 2.6% versus O: 4.8%, P = 0.651). For patients with penetrating injuries (n = 110), the endovascular repair had significantly lower morbidity (19% versus 41%, P = 0.034) and mortality (3.7% versus 21%, P = 0.041). On multivariable logistic regression, endovascular repair was identified as the only modifiable risk factor associated with reduced mortality (adjusted odds ratio: 0.201, 95% confidence interval [0.14-0.76], P = 0.038). CONCLUSIONS: Difficult-to-access vascular injuries result in significant morbidity and mortality. Endovascular repair was found to be the only modifiable factor associated with decreased mortality of patients with penetrating injury, whereas the type of repair was not associated with mortality in those with blunt injury.

The Harsh Reality: Outcomes of Patients With Operatively Managed Lung Injuries.

INTRODUCTION: Most traumatic lung injuries are managed non-operatively. There is a paucity of recent data on the outcomes of operatively managed lung injuries. The aim of our study is to determine the survival rates of operatively managed traumatic lung injury patients on a nationwide scale. METHODS: We performed a retrospective analysis of the ACS-TQIP 2017-2020. We included all adult trauma patients with lung injuries that underwent operative management. Patients were stratified based on type of surgery into 3 groups (wedge resection, lobectomy, pneumonectomy). The outcome was mortality. Multivariable logistic regression analysis was performed to identify the independent predictors of mortality. RESULTS: We identified a total of 170,377 patients with lung injuries, out of which 2159 (1.3%) patients underwent operative management (Wedge resection [61%], Lobectomy [31%], Pneumonectomy [8%]). Among operatively managed patients, the mean (SD) age was 37 (16) years, and 86% were male. Overall, 65% sustained penetrating injuries, with a median [IQR] ISS of 25 [16 - 33], and median [IQR] lung injury AIS severity of 4 [3 - 4]. About 7% of the patients suffered hilar injuries. The mean (SD) SBP on arrival was 108 (43) and the median [IQR] time to surgery was 177 [52 - 5351] minutes. The median hospital LOS was 10 [1 - 19] days, and overall mortality rate was 30%. On univariate analysis, patients undergoing pneumonectomy had the highest mortality (54%), followed by lobectomy (33%), and wedge resection (25%). On multivariable regression analysis, hilar injuries (aOR 1.9, 95%CI = 1.06 - 2.80, P = 0.029), increasing age (aOR 1.02, 95%CI = 1.01 - 1.03, P = 0.001), concomitant head (aOR 1.34, 95%CI = 1.22 - 1.47, P < 0.001) and abdominal injuries (aOR 1.42, 95%CI = 1.31 - 1.54, P < 0.001) were independent predictors of mortality. CONCLUSIONS: Nearly 1 in 3 patients with lung injuries who were managed operatively did not survive their index admission. These findings highlight that operatively managed lung injuries still carry a high risk of mortality and should be reserved for selected patients. The decision for surgery in patients with concomitant head or abdominal injuries must be taken on a case-to-case basis.

Development and Validation of Futility of Resuscitation Measure in Older Adult Trauma Patients.

INTRODUCTION: This study aimed to develop and validate Futility of Resuscitation Measure (FoRM) for predicting the futility of resuscitation among older adult trauma patients. METHODS: This is a retrospective analysis of the American College of Surgeons-Trauma Quality Improvement Program database (2017-2018) (derivation cohort) and American College of Surgeons level I trauma center database (2017-2022) (validation cohort). We included all severely injured (injury severity score >15) older adult (aged ≥60 y) trauma patients. Patients were stratified into decades of age. Injury characteristics (severe traumatic brain injury [Glasgow Coma Scale ≤ 8], traumatic brain injury midline shift), physiologic parameters (lowest in-hospital systolic blood pressure [≤1 h], prehospital cardiac arrest), and interventions employed (4-h packed red blood cell transfusions, emergency department resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta, emergency laparotomy [≤2 h], early vasopressor requirement [≤6 h], and craniectomy) were identified. Regression coefficient-based weighted scoring system was developed using the Schneeweiss method and subsequently validated using institutional database. RESULTS: A total of 5562 patients in derivation cohort and 873 in validation cohort were identified. Mortality was 31% in the derivation cohort and FoRM had excellent discriminative power to predict mortality (area under the receiver operator characteristic = 0.860; 95% confidence interval [0.847-0.872], P < 0.001). Patients with a FoRM score of >16 had a less than 10% chance of survival, while those with a FoRM score of >20 had a less than 5% chance of survival. In validation cohort, mortality rate was 17% and FoRM had good discriminative power (area under the receiver operator characteristic = 0.76; 95% confidence interval [0.71-0.80], P < 0.001). CONCLUSIONS: FoRM can reliably identify the risk of futile resuscitation among older adult patients admitted to our level I trauma center.