Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

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). SUMMARY BACKGROUND DATA: 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. Cohen's κ statistic was used to assess concordance between ATV and procedural volume. RESULTS: 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. 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. Cohen's 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). CONCLUSION: 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.

Predicting the time of mortality among older adult trauma patients: Is frailty the answer?

INTRODUCTION: This study aims to evaluate the temporal trends of mortality among frail versus non-frail older adult trauma patients during index hospitalization. METHODS: We performed a 3-year (2017-2019) analysis of ACS-TQIP. We included all older adult (age ≥65 years) trauma patients. Patients were stratified into two groups (Frail vs. Non-Frail). Outcomes were acute (<24 â€‹h), early (24-72 â€‹h), intermediate (72 hours-1 week), and late (>1 week) mortality. RESULTS: A total of 1,022,925 older adult trauma patients were identified, of which 19.7 â€‹% were frail. The mean(SD) age was 77(8) years and 57.4 â€‹% were female. Median[IQR] ISS was 9[4-10] and both groups had comparable injury severity (p â€‹= â€‹0.362). On multivariable analysis, frailty was not associated with acute (aOR 1.034; p â€‹= â€‹0.518) and early (aOR 1.190; p â€‹= â€‹0.392) mortality, while frail patients had independently higher odds of intermediate (aOR 1.269; p â€‹= â€‹0.042) and late (aOR 1.835; p â€‹< â€‹0.001) mortality. On sub-analysis, our results remained consistent in mild, moderate, and severely injured patients. CONCLUSION: Frailty is an independent predictor of mortality in older adult trauma patients who survive the initial 3 days of admission, regardless of injury severity.

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.

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.

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.

Impact of Resuscitation Adjuncts on Post-Intubation Hypotension in Patients with Isolated TBI.

INTRODUCTION: Post-intubation hypotension (PIH) is a risk factor of endotracheal intubation (ETI) after injury. For those with traumatic brain injury (TBI), one episode of hypotension can potentiate that injury. This study aims to identify the resuscitation adjuncts which may decrease the incidence of PIH in this patient population. METHODS: This is a 4-year (2019-2022) prospective observational study at a level I trauma center. Adult (≥18) patients with isolated TBI requiring ETI in the trauma bay were included. Blood pressures were measured 15 minutes pre- and post-intubation. Primary outcome was PIH, defined as a decrease in SBP ≥ 20% from baseline or to<80 mmHg, or any decrease in MAP to ≤60 mmHg. Multivariable logistic regression was performed to identify the associations of pre-intubation vasopressor, hypertonic saline (HTS), PRBC, and crystalloids on PIH incidence. RESULTS: Of the 490 enrolled patients, 16% had mild (Head AIS ≤ 2), 35% moderate (Head AIS 3-4), and 49% severe (Head AIS ≥ 5) TBI. Mean age was 42 ± 22 years and 71% were male. Median ISS, head-AIS, and GCS were 26[19-38], 4[3-5], and 6[3-11], respectively. Mean SBP 15 minutes pre- and post-intubation were 118 ± 46 and 106 ± 45, respectively. Before intubation, 31% received HTS, 10% vasopressors, 20% crystalloids, and 14% at least one unit of PRBC (median, 2[1-2]U). Overall, 304 (62%) patients developed PIH. On multivariable regression analysis, pre-intubation use of vasopressors and HTS were associated with significantly decreased odds of PIH independent of TBI severity, 0.310 (0.102-0.944, p = 0.039) and 0.393 (0.219-0.70, p = 0.002) respectively. CONCLUSIONS: Nearly two-thirds of isolated TBI patients developed PIH. Pre-intubation vasopressors and HTS are associated with a decreased incidence of PIH. Such adjuncts should be considered prior to ETI in patients with suspected TBI. LEVEL OF EVIDENCE: III; Prospective Observational.

Surgical stabilization of rib fractures: The impact of volume and the need for standardized indications.

INTRODUCTION: We aimed to examine impact of trauma center (TC) surgical stabilization of rib fracture (SSRF) volume on outcomes of patients undergoing SSRF. METHODS: Blunt rib fracture patients who underwent SSRF were included from ACS-TQIP2017-2021. TCs were stratified according to tertiles of SSRF volume:low (LV), middle, and high (HV). Outcomes were time to SSRF, respiratory complications, prolonged ventilator use, mortality. RESULTS: 16,872 patients were identified (LV:5470,HV:5836). Mean age was 56 years, 74% were male, median thorax-AIS was 3. HV centers had a lower proportion of patients with flail chest (HV41% vs LV50%), pulmonary contusion (HV44% vs LV52%) and had shorter time to SSRF(HV58 vs LV76 â€‹h), less respiratory complications (HV3.2% vs LV4.5%), prolonged ventilator use (HV15% vs LV26%), mortality (HV2% vs LV2.6%) (all p â€‹< â€‹0.05). On multivariable regression analysis, HV centers were independently associated with reduced time to SSRF(ߠ​= â€‹-18.77,95%CI â€‹= â€‹-21.30to-16.25), respiratory complications (OR â€‹= â€‹0.67,95%CI â€‹= â€‹0.49-0.94), prolonged ventilator use (OR â€‹= â€‹0.49,95%CI â€‹= â€‹0.41-0.59), but not mortality. CONCLUSIONS: HV SSRF centers have improved outcomes, however, there are variations in threshold for SSRF and indications must be standardized. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic/Care Management.

Effect of PCC on outcomes of severe traumatic brain injury patients on preinjury anticoagulation.

INTRODUCTION: This study aims to evaluate effect of 4-factor PCC on outcomes of severe TBI patients on preinjury anticoagulants undergoing craniotomy/craniectomy. METHODS: In this analysis of 2018-2020 ACS-TQIP, patients with isolated blunt severe TBI (Head-AIS≥3, nonhead-AIS<2) using preinjury anticoagulants who underwent craniotomy/craniectomy were identified and stratified into PCC and No-PCC groups. Outcomes were time to surgery and mortality. Multivariable binary logistic and linear regression analyses were performed. RESULTS: 1598 patients were identified (PCC-107[7 %], No-PCC-1491[93 %]). Mean age was 74(11) years, 65 % were male, median head AIS was 4. Median time to PCC administration was 109 â€‹min. On univariable analysis, PCC group had shorter time to surgery (PCC-341, No-PCC-620 â€‹min, p â€‹= â€‹0.002), but higher mortality (PCC35 %, No-PCC21 %,p â€‹= â€‹0.001). On regression analysis, PCC was independently associated with shorter time to surgery (ߠ​= â€‹-1934,95 %CI â€‹= â€‹-3339to-26), but not mortality (aOR â€‹= â€‹0.70,95 %CI â€‹= â€‹0.14-3.62). CONCLUSION: PCC may be a safe adjunct for urgent reversal of coagulopathy in TBI patients using preinjury anticoagulants.

Improving medication adherence in cardiovascular disease.

Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.

It is not all black and white: The effect of increasing severity of frailty on outcomes of geriatric trauma patients.

BACKGROUND: Frailty is associated with poor outcomes in trauma patients. However, the spectrum of physiologic deficits, once a patient is identified as frail, is unknown. The aim of this study was to assess the dynamic association between increasing frailty and outcomes among frail geriatric trauma patients. METHODS: This is a secondary analysis of the American Association of Surgery for Trauma Frailty Multi-institutional Trial. Patients 65 years or older presenting to one of the 17 trauma centers over 3 years (2019-2022) were included. Frailty was assessed within 24 hours of presentation using the Trauma-Specific Frailty Index (TSFI) questionnaire. Patients were stratified by TSFI score into six groups: nonfrail (<0.12), Grade I (0.12-0.19), Grade II (0.20-0.29), Grade III (0.30-0.39), Grade IV (0.40-0.49), and Grade V (0.50-1). Our Outcomes included in-hospital and 3-month postdischarge mortality, major complications, readmissions, and fall recurrence. Multivariable regression analyses were performed. RESULTS: There were 1,321 patients identified. The mean (SD) age was 77 years (8.6 years) and 49% were males. Median [interquartile range] Injury Severity Score was 9 [5-13] and 69% presented after a low-level fall. Overall, 14% developed major complications and 5% died during the index admission. Among survivors, 1,116 patients had a complete follow-up, 16% were readmitted within 3 months, 6% had a fall recurrence, 7% had a complication, and 2% died within 3 months postdischarge. On multivariable regression, every 0.1 increase in the TSFI score was independently associated with higher odds of index-admission mortality and major complications, and 3 months postdischarge mortality, readmissions, major complications, and fall recurrence. CONCLUSION: The frailty syndrome goes beyond a binary stratification of patients into nonfrail and frail and should be considered as a spectrum of increasing vulnerability to poor outcomes. Frailty scoring can be used in developing guidelines, patient management, prognostication, and care discussions with patients and their families. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

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.

Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. METHOD: A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. RESULTS: Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. CONCLUSIONS: History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Cardiovascular Effects of GnRH Antagonists Compared With Agonists in Prostate Cancer: A Systematic Review.

Background: Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists. Objectives: This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists. Methods: Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: "myocardial infarction," "central nervous system hemorrhages and cerebrovascular conditions," and all-cause mortality. Bayesian meta-analysis models with random effects were fitted. Results: A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death. Conclusions: Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.

Local Antibiotic Therapy for Open Long Bone Fractures: Appropriate Prophylaxis or Unnecessary Exposure for the Orthopedic Trauma Patient?

INTRODUCTION: Prophylactic local antibiotic therapy (LAbT) to prevent infection in open long bone fracture (OLBF) patients has been in use for many decades despite lack of definitive evidence confirming a beneficial effect. We aimed to evaluate the effect of LAbT on outcomes of OLBF patients on a nationwide scale. MATERIALS AND METHODS: In this retrospective analysis of 2017-2018 American College of Surgeons-Trauma Quality Improvement Program database, all adult (≥18 years) patients with isolated OLBF (non-extremity-Abbreviated Injury Scale < 3) were included. We excluded early deaths (<24 h) and those who had burns or non-extremity surgery. Outcomes were infectious complications (superficial surgical site infection, deep superficial surgical site infection, osteomyelitis, or sepsis), unplanned return to operating room, and hospital and intensive care unit length of stay (LOS). Patients were stratified into two groups: those who received LAbT and those who did not receive LAbT (No-LAbT). Propensity score matching (1:3) and chi-square tests were performed. RESULTS: A total of 61,337 isolated OLBF patients were identified, among whom 2,304 patients were matched (LAbT: 576; No-LAbT: 1,728). Both groups were similar in terms of baseline characteristics. Mean age was 43 ± 17 years, 75% were male, 14% had penetrating injuries, and the median extremity-Abbreviated Injury Scale was 1 (1-2). Most common fracture locations were tibia (66%), fibula (49%), femur (24%), and ulna (11%). About 52% of patients underwent external fixation, 79% underwent internal fixation, and 86% underwent surgical debridement. The median time to LAbT was 17 (5-72) h, and the median time to debridement was 7 (3-15) h (85% within 24 h). The LAbT group had similar rates of infectious complications (3.5% vs. 2.5%, P = 0.24) and unplanned return to the operating room (2.3% vs. 2.0%, P = 0.74) compared to the No-LAbT group. Patients who received LAbT had longer hospital LOS (16 [10-29] vs. 14 [9-24] days, P < 0.001) but similar intensive care unit LOS (4 [3-9] vs. 4 [2-7] days, P = 0.19). CONCLUSIONS: Our findings indicate that prophylactic LAbT for OLBF may not be beneficial over well-established standards of care such as early surgical debridement and systemic antibiotics. Prospective studies evaluating the efficacy, risks, costs, and indications of adjuvant LAbT for OLBF are warranted.

Delayed versus early hepatic resection among patients with severe traumatic liver injuries undergoing damage control laparotomy.

INTRODUCTION: We aimed to assess the effect of time to hepatic resection on the outcomes of patients with high-grade liver injuries who underwent damage control laparotomy (DCL). METHODS: This is a 4-year (2017-2020) analysis of the ACS-TQIP. Adult trauma patients with severe liver injuries (AAST-OIS grade â€‹≥ â€‹III) who underwent DCL and hepatic resection were included. We excluded patients with early mortality (<24 â€‹h). Patients were stratified into those who received hepatic resection within the initial operation (Early) and take-back operation (Delayed). RESULTS: Of 914 patients identified, 29% had a delayed hepatic resection. On multivariable regression analyses, although delayed resection was not associated with mortality (aOR:1.060,95%CI[0.57-1.97],p â€‹= â€‹0.854), it was associated with higher complications (aOR:1.842,95%CI[1.38-2.46],p â€‹< â€‹0.001), and longer hospital (ß: +0.129, 95%CI[0.04-0.22],p â€‹= â€‹0.005) and ICU (ß:+0.198,95%CI[0.14-0.25],p â€‹< â€‹0.001) LOS, compared to the early resection. CONCLUSION: Delayed hepatic resection was associated with higher adjusted odds of major complications and longer hospital and ICU LOS, however, no difference in mortality, compared to early resection.

From surveillance to surgery: The delayed implications of non-operative and operative management of pancreatic injuries.

BACKGROUND: Our study compares the delayed outcomes of operative versus nonoperative management of pancreatic injuries. METHODS: We analyzed the 2017 Nationwide Readmissions Database on adult (≥18 years) trauma patients with pancreatic injuries. Patients who died on index admission were excluded. Patients were stratified into operative (OP) and non-operative (NOP) groups and compared for outcomes within 90 days of discharge. Multivariable regression analyses were performed. RESULTS: We identified 1553 patients (NOP â€‹= â€‹1092; OP â€‹= â€‹461). The Mean (SD) age was 39 (17.0) years, 31% of patients were female, and 77% had blunt injuries. Median ISS was 17 [9-25] and 74% had concomitant non-pancreatic intraabdominal injuries. On multivariable analysis, operative management was independently associated with increased odds of 90-day readmissions (aOR â€‹= â€‹1.47; p â€‹= â€‹0.03), intraabdominal abscesses (aOR â€‹= â€‹2.7; p â€‹< â€‹0.01), pancreatic pseudocyst (aOR â€‹= â€‹2.4; p â€‹= â€‹0.04), and need for percutaneous or endoscopic management (aOR â€‹= â€‹5.8; p â€‹< â€‹0.001). CONCLUSION: Operative management of pancreatic injuries is associated with higher rates of delayed complications compared to non-operative management. Surgically treated pancreatic trauma patients may need close surveillance even after discharge.

The undisclosed disclosures: The dollar-outcome relationship in resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Despite its rapid evolution, resuscitative endovascular balloon occlusion of the aorta (REBOA) remains a controversial intervention that continues to generate active research. Proper conflict of interest (COI) disclosure helps to ensure that research is conducted objectively, without bias. We aimed to identify the accuracy of COI disclosures in REBOA research. METHODS: Literature search was performed using the keyword "REBOA" on PubMed. Studies on REBOA with at least one American author published between 2017 and 2022 were identified. The Centers for Medicare and Medicaid Services Open Payments database was used to extract information regarding payments to the authors from the industry. This was compared with the COI section reported in the manuscripts. Conflict of interest disclosure was defined as inaccurate if the authors failed to disclose any amount of money received from the industry. Descriptive statistics were performed. RESULTS: We reviewed a total of 524 articles, of which 288 articles met the inclusion criteria. At least one author received payments in 57% (165) of the articles. Overall, 59 authors had a history of payment from the industry. Conflict of interest disclosure was inaccurate in 88% (145) of the articles where the authors received payment. CONCLUSION: Conflict of interest reports are highly inaccurate in REBOA studies. There needs to be standardization of reporting of conflicts of interest to avoid potential bias. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.