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INTRODUCTION: Resuscitative thoracotomy (RT) in the setting of traumatic arrest serves as a vital but resource-intensive intervention. The COVID-19 pandemic has created critical shortages, sharpening the focus on efficient resource utilization. This study aims to compare RT performance and blood product utilization before and after the onset of the COVID-19 pandemic for patients in traumatic cardiac arrest. METHODS: All patients undergoing RT for traumatic cardiac arrest in the emergency department at our American College of Surgeons-verified Level 1 trauma center (August 01, 2017-July 31, 2022) were included in this retrospective observational study. Study groups were dichotomized into pre-COVID (before October 03, 2020) versus COVID (from October 03, 2020 on) based on patient arrival date demographics, clinical/injury data, and outcomes were collected. The primary outcome was blood product transfusion <4 h after presentation. RESULTS: 445 RTs (2% of 23,488 trauma encounters) were performed over the study period: Pre-COVID, n = 209 (2%) versus COVID, n = 236 (2%) (P = 0.697). Survival to discharge was equivalent Pre-COVID versus COVID (n = 22, 11% versus n = 21, 9%, P = 0.562). RT patients during COVID consumed a median of 1 unit less packed red blood cells at the 4 h measurement (3.0 [1.8-7.0] versus 3.9 [2.0-10.0] units, P = 0.012) and 1 unit less of platelets at the 4 h measurement (4.3 [2.6-10.0] versus 5.7 [2.9-14.4] units, P = 0.012) compared to Pre-COVID. These findings were persistent after performing multivariable negative binomial regression. CONCLUSIONS: Rates of RT and survival after RT remained consistent during the pandemic. Despite comparable RT frequency, packed red blood cells and platelet transfusions were reduced, likely reflecting resource expenditure minimization during the severe blood shortages that occurred during the pandemic. RT performance for patients in traumatic arrest may, therefore, be feasible during global pandemics at prepandemic frequencies as long as particular attention is paid to resource expenditure.
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COVID-19 , Heart Arrest , Humans , Thoracotomy , Pandemics , Injury Severity Score , Resuscitation , Retrospective Studies , COVID-19/epidemiologySubject(s)
Brain Injuries, Traumatic , Cerebrovascular Circulation , Homeostasis , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/therapy , Homeostasis/physiology , Humans , Cerebrovascular Circulation/physiology , Brain/metabolism , Oxygen/metabolismABSTRACT
Trauma and acute care surgeons commonly perform high acuity and emergent interventions on critically ill or injured patients. This often entails making life or death decisions rapidly and with incomplete and imperfect information, and in patients who may have a variety of comorbidities that contribute to the risk of adverse outcomes. In cases where there are real or perceived breaches of care, a medical malpractice claim may result. In the USA, approximately one-third to one-half of all physicians will be named in medical litigation at least once in their career. Among the various specialties, surgery remains among the highest risk for malpractice litigation, at an average of 10.6 defendants per 100 surgeons. These events can be extremely stressful, demoralizing, or even devastating to the career and well-being of the involved physicians. This can be made better or worse by the individual response and actions of the surgeon on notification of a real or potential claim, and the primary goal of this review is to highlight these key areas and optimal strategies in malpractice scenarios. This includes strategies to manage the initial receipt of a malpractice claim, subsequent courses of action, and advice for incorporating preventive measures into everyday practice.
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ABSTRACT: Decades of research have provided insight into the benefits of nutritional optimization in the elective surgical patient. Patients who are nutritionally prepared for surgery enjoy reduced length of hospital and intensive care unit stays and suffer fewer complications. In the trauma and emergency general surgery patient populations, we are not afforded the preoperative period of optimization and patients often suffer longer lengths of hospital stay, discharge to nonhome destinations, and higher infectious and mortality rates. Nonetheless, ongoing research in this vulnerable and time critical diagnosis population has revealed significant outcomes benefits with the meticulous nutritional support of these patients. However, it is important to note that optimal nutritional support in this challenging patient population is not simply a matter of "feeding more and feeding earlier." In this review, we will address assessing nutritional needs, the provision of optimal nutrition, the timing and route of nutrition, and monitoring outcomes and discuss the management of nutrition in the complex trauma and emergency general surgery patient. LEVEL OF EVIDENCE: Literature Synthesis and Expert Opinion; Level V.
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Nutritional Support , Wounds and Injuries , Humans , Nutritional Support/methods , Wounds and Injuries/surgery , Wounds and Injuries/therapy , Wounds and Injuries/complications , Nutrition Assessment , Nutritional Status , General Surgery , Acute Care SurgeryABSTRACT
The primary ethical principle guiding general medical practice is autonomy. However, in mass casualty (MASCAL) or disaster scenarios, the principles of beneficence and justice become of foremost concern. Despite multiple reviews, publications, and training courses available to prepare for a MASCAL incident, a minority of physicians and healthcare providers are abreast of these. In this review, we describe several MASCAL scenarios and their associated ethical, moral, and medicolegal quandaries in attempts to curb potential future misadventures.
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Robotic surgery was first introduced in the 1980s as a system to aid patients in the battlefield. Since then, robotic surgery has become an important minimally invasive tool and plays an important role in elective surgery among various surgical specialties. However, the role for robotic surgery in the emergent setting is not well established or studied. Robotic surgery has been shown to be advantageous to both patients and operating surgeons. Though limited, studies have found robotic surgery in the acute setting to be safe for patients. These studies found robotic surgery to have improved perioperative outcomes when compared to an open or laparoscopic approach. Additionally, the robotic platform is thought to be an effective tool to prevent conversion to open procedures in emergent settings. Although some studies demonstrate advantages to robotic acute surgery, others have shown increased complications with robotic acute surgery or no distinct advantage when comparing robotic to laparoscopic surgery. Additionally, some of the published papers supporting the use of robotic surgery in the emergent setting may have a degree of bias favoring the robotic platform. Robotic surgery is a mainstay in minimally invasive elective surgery and gaining popularity among patients and surgeons. There are pros and cons to the adaptation of the robotic platform in the acute care setting. Additional large population studies are indicated to determine the true role of the robotic platform in the emergent setting.
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Background: Bile duct injury (BDI) is one of the most severe complications during cholecystectomy. Early identification of risk factors for BDI may permit risk reduction strategies and inform patient consent.Objective: This study aimed to define patient, provider, and systemic factors associated with BDI; BDI incidence; and short-term outcomes of BDI after urgent cholecystectomy.Methods: Patients who underwent urgent cholecystectomy for acute cholecystitis were retrospectively screened (2020-2022). All patients who sustained BDI were included without exclusions. Demographics, clinical data, and outcomes were collected and compared with descriptive statistics.Results: During the study period, BDI occurred in 4 (0.5%) of 728 patients who underwent urgent cholecystectomy for acute cholecystitis. Most BDI cases (75%) took place overnight or during the weekend. The attending surgeon was almost exclusively (75%) in their first year of practice. BDI was recognized during index operation in 2 cases (50%). Hepatobiliary surgery performed the bile duct repair in all 4 cases. Two complications occurred (50%). All patients were followed by hepatobiliary surgery in the outpatient setting and returned to their baseline level of function within 2 months of hospital discharge.Conclusion: Most BDI occurred in procedures attended by first-year faculty during after hours cholecystectomies, suggesting a role for increased proctorship in early career attendings in addition to in-hours cholecystectomy for acute cholecystitis. The timely return to baseline function experienced by these patients emphasizes the favorable outcomes associated with early recognition of BDI and involvement of hepatobiliary surgery. Further examination with multicenter evaluation would be beneficial to validate these study findings.
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Introduction: The analysis of surgical research using bibliometric measures has become increasingly prevalent. Absolute citation counts (CC) or indices are commonly used markers of research quality but may not adequately capture the most impactful research. A novel scoring system, the disruptive score (DS) has been found to identity academic work that either changes paradigms (disruptive (DIS) work) or entrenches ideas (developmental (DEV) work). We sought to analyze the most DIS and DEV versus most cited research in civilian trauma. Methods: The top papers by DS and by CC from trauma and surgery journals were identified via a professional literature search. The identified publications were then linked to the National Institutes of Health iCite tool to quantify total CC and related metrics. The top 100 DIS and DEV publications by DS were analyzed based on the area of focus, citation, and perceived clinical impact, and compared with the top 100 papers by CC. Results: 32 293 articles published between 1954 and 2014 were identified. The most common publication location of selected articles was published in Journal of Trauma (31%). Retrospective reviews (73%) were common in DIS (73%) and top CC (67%) papers, while DEV papers were frequently case reports (49%). Only 1 publication was identified in the top 100 DIS and top 100 CC lists. There was no significant correlation between CC and DS among the top 100 DIS papers (r=0.02; p=0.85), and only a weak correlation between CC and DS score (r=0.21; p<0.05) among the top 100 DEV papers. Conclusion: The disruption score identifies a unique subset of trauma academia. The most DIS trauma literature is highly distinct and has little overlap with top trauma publications identified by standard CC metrics, with no significant correlation between the CC and DS. Level of evidence: Level IV.
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BACKGROUND: The optimal management of pediatric patients with high-grade blunt pancreatic injury (BPI) involving the main pancreatic duct remains controversial. This study aimed to assess the nationwide trends in the management of pediatric high-grade BPI at pediatric (PTC), mixed (MTC), and adult trauma centers (ATC). STUDY DESIGN: This is a retrospective observational study of the National Trauma Data Bank. We included pediatric patients (age 16 years or less) sustaining high-grade BPI (Abbreviated Injury Scale 3 or more) from 2011 to 2021. Patients who did not undergo pancreatic operation were categorized into the nonoperative management (NOM) group. Trauma centers were defined as PTC (level I/II pediatric only), MTC (level I/II adult and pediatric), and ATC (level I/II adult only). Primary outcome was the proportion of patients undergoing NOM, and secondary outcomes included the use of ERCP and in-hospital mortality. A Cochran-Armitage test was used to analyze the trend. RESULTS: A total of 811 patients were analyzed. The median age was 9 years (interquartile range 6 to 13), 64% were male patients, and the median injury severity score was 17 (interquartile range 10 to 25). During the study period, there was a significant upward linear trend in the use of NOM and ERCP among the overall cohort (range 48% to 66%; p trend = 0.033, range 6.1% to 19%; p trend = 0.030, respectively). The significant upward trend for NOM was maintained in the subgroup of patients at PTC and MTC (p trend = 0.037), whereas no significant trend was observed at ATC (p trend = 0.61). There was no significant trend in in-hospital mortality (p trend = 0.38). CONCLUSIONS: For the management of pediatric patients with high-grade BPI, this study found a significant trend toward increasing use of NOM and ERCP without mortality deterioration, especially at PTC and MTC.
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Injury Severity Score , Pancreas , Wounds, Nonpenetrating , Humans , Wounds, Nonpenetrating/therapy , Wounds, Nonpenetrating/mortality , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/surgery , Male , Female , Retrospective Studies , Child , Adolescent , Pancreas/injuries , Pancreas/surgery , Trauma Centers/statistics & numerical data , Hospital Mortality/trends , United States/epidemiology , Cholangiopancreatography, Endoscopic Retrograde/statistics & numerical data , Child, Preschool , Abdominal Injuries/therapy , Abdominal Injuries/mortality , Abdominal Injuries/diagnosis , Abdominal Injuries/surgeryABSTRACT
INTRODUCTION: An increasing proportion of the population identifies as non-binary. This marginalized group may be at differential risk for trauma compared to those who identify as male or female, but physical trauma among non-binary patients has not yet been examined at a national level. METHODS: All patients aged ≥ 16 years in the National Trauma Data Bank were included (2021-2022). Demographics, injury characteristics, and outcomes after trauma among non-binary patients were compared to males and females. The goal was to delineate differences between groups to inform the care and future study of non-binary trauma patients. RESULTS: In total, 1,012,348 patients were included: 283 (<1%) non-binary, 610,904 (60%) male, and 403,161 (40%) female patients. Non-binary patients were younger than males or females (median age 44 vs 49 vs 67 years, P < .001) and less likely to be White race/ethnicity (58% vs 60% vs 74%, P < .001). Despite non-binary patients having a lower median Injury Severity Score (5 vs 9 vs 9, P < .001), mortality was highest among non-binary and male patients than females (5% vs 5% vs 3%, P < .001). DISCUSSION: In this study, non-binary trauma patients were younger and more likely minority races/ethnicities than males or females. Despite having a lower injury severity, non-binary patient mortality rates were comparable to those of males and greater than for females. These disparities identify non-binary trauma patients as doubly marginalized, by gender and race/ethnicity, who experience worse outcomes after trauma than expected based on injury severity. This vulnerable patient population deserves further study to identify areas for improved trauma delivery care.
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INTRODUCTION: Emergent laparotomy is associated with significant wound complications including surgical site infections (SSIs) and fascial dehiscence. Triclosan-coated barbed (TCB) suture for fascial closure has been shown to reduce local complications but primarily in elective settings. We sought to evaluate the effect of TCB emergency laparotomy fascial closure on major wound complications. METHODS: Adult patients undergoing emergency laparotomy were prospectively evaluated over 1 year. Patients were grouped into TCB versus polydioxanone (PDS) for fascial closure. Subanalysis was performed on patients undergoing single-stage laparotomy. Primary outcomes were SSI and fascial dehiscence. Multivariate analysis identified independent factors associated with SSI and fascial dehiscence. RESULTS: Of the 206 laparotomies, 73 (35%) were closed with TCB, and 133 (65%) were closed with PDS. Trauma was the reason for laparotomy in 73% of cases; damage-control laparotomy was performed in 27% of cases. The overall rate of SSI and fascial dehiscence was 18% and 10%, respectively. Operative strategy was similar between groups, including damage-control laparotomy, wound vac use, skin closure, and blood products. Surgical site infection events trended lower with TCB versus PDS closure (11% vs. 21%, p = 0.07), and fascial dehiscence was significantly lower with TCB versus PDS (4% vs. 14%, p < 0.05). Subanalysis of trauma and nontrauma cases showed no difference in SSI or fascial dehiscence. Multivariable analysis found that TCB decreased the likelihood of fascial dehiscence (odds ratio, 0.07; p < 0.05) following emergency laparotomy. Increased odds of fascial dehiscence were seen in damage-control laparotomy (odds ratio, 3.1; p < 0.05). CONCLUSION: Emergency laparotomy fascial closure with TCB showed significantly decreased rates of fascial dehiscence compared with closure with PDS and a strong trend toward lower SSI events. Triclosan-coated barbed suture was independently associated with decreased fascial dehiscence rates after emergency laparotomy. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.
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Laparotomy , Surgical Wound Dehiscence , Surgical Wound Infection , Sutures , Triclosan , Humans , Male , Female , Triclosan/administration & dosage , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Laparotomy/methods , Laparotomy/adverse effects , Surgical Wound Dehiscence/prevention & control , Surgical Wound Dehiscence/etiology , Surgical Wound Dehiscence/epidemiology , Prospective Studies , Middle Aged , Adult , Anti-Infective Agents, Local/administration & dosage , Suture Techniques/instrumentation , Polydioxanone , Treatment OutcomeABSTRACT
PURPOSE: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease progression. EXPERIMENTAL DESIGN: ctDNA profiling analysis on-progression plasma samples from patients treated with osimertinib in both first (Phase 3, FLAURA trial) and second-line trials (Phase 3, AURA3 trial) revealed a high prevalence of PIK3CA/AKT/PTEN alterations. In vitro and in vivo evidence using CRISPR engineered NSCLC cell lines and PXD models support a functional role for PIK3CA and PTEN mutations in the development of osimertinib resistance. RESULTS: These alterations are functionally relevant as EGFRm NSCLC cells with engineered PIK3CA/AKT/PTEN alterations develop resistance to osimertinib and can be re-sensitized by treatment with the combination of osimertinib and the AKT inhibitor capivasertib. Moreover, xenograft and PDX in vivo models with PIK3CA/AKT/PTEN alterations display limited sensitivity to osimertinib relative to models without alteration, and in these double mutant models capivasertib and osimertinib combination elicits an improved anti-tumor effect versus osimertinib alone. CONCLUSIONS: Together, this approach offers a potential treatment strategy for patients with EGFRm-driven NSCLC that have a sub-optimal response, or develop resistance, to osimertinib through PIK3CA/AKT/PTEN alterations.
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BACKGROUND: Algorithms for managing penetrating abdominal trauma are conflicting or vague regarding the role of laparoscopy. We hypothesized that laparoscopy is underutilized among hemodynamically stable patients with abdominal stab wounds. METHODS: Trauma Quality Improvement Program data (2016-2019) were used to identify stable (SBP ≥110 and GCS ≥13) patients ≥16yrs with stab wounds and an abdominal procedure within 24hr of admission. Patients with a non-abdominal AIS ≥3 or missing outcome information were excluded. Patients were analyzed based on index procedure approach: open, therapeutic laparoscopy (LAP), or LAP-conversion to open (LCO). Center, clinical characteristics and outcomes were compared according to surgical approach and abdominal AIS using non-parametric analysis. RESULTS: 5984 patients met inclusion criteria with 7 â% and 8 â% receiving therapeutic LAP and LCO, respectively. The conversion rate for patients initially treated with LAP was 54 â%. Compared to conversion or open, therapeutic LAP patients had better outcomes including shorter ICU and hospital stays and less infection complications, but were younger and less injured. Assessing by abdominal AIS eliminated ISS differences, meanwhile LAP patients still had shorter hospital stays. At time of admission, 45 â% of open patients met criteria for initial LAP opportunity as indicated by comparable clinical presentation as therapeutic laparoscopy patients. CONCLUSIONS: In hemodynamically stable patients, laparoscopy remains infrequently utilized despite its increasing inclusion in current guidelines. Additional opportunity exists for therapeutic laparoscopy in trauma, which appears to be a viable alternative to open surgery for select injuries from abdominal stab wounds. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.
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Abdominal Injuries , Laparoscopy , Wounds, Penetrating , Wounds, Stab , Humans , Laparotomy , Retrospective Studies , Wounds, Stab/surgery , Wounds, Penetrating/surgery , Laparoscopy/methods , Abdominal Injuries/diagnosis , Abdominal Injuries/surgery , Abdominal Injuries/etiologyABSTRACT
PURPOSE: COVID-19 patients with respiratory failure frequently require prolonged ventilatory support that would typically warrant early tracheostomy. There has been significant debate on timing, outcomes, and safety of these procedures. The purpose of this study was to determine the epidemiological, hospital, and post-discharge outcomes of this cohort, based on early (ET) versus late (LT) tracheostomy. METHODS: Retrospective review (March 2020-January 2021) in a 5-hospital system of ventilated patients who underwent tracheostomy. Demographics, hospital/ICU length of stay (LOS), procedural characteristics, APACHE II scores at ICU admission, stabilization markers, and discharge outcomes were analyzed. Long-term decannulation rates were obtained from long-term acute care facility (LTAC) data. RESULTS: A total of 97 patients underwent tracheostomy (mean 61 years, 62% male, 64% Hispanic). Despite ET being frequently performed during active COVID infection (85% vs. 64%), there were no differences in complication types or rates versus LT. APACHE II scores at ICU admission were comparable for both groups; however, > 50% of LT patients met PEEP stability at tracheostomy. ET was associated with significantly shorter ICU and hospital LOS, ventilator days, and higher decannulation rates. Of the cohort discharged to an LTAC, 59% were ultimately decannulated, 36% were discharged home, and 41% were discharged to a skilled nursing facility. CONCLUSIONS: We report the first comprehensive analysis of ET and LT that includes LTAC outcomes and stabilization markers in relation to the tracheostomy. ET was associated with improved clinical outcomes and a short LOS, specifically on days of pre-tracheostomy ventilation and in-hospital decannulation rates.
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COVID-19 , Length of Stay , Patient Discharge , Respiration, Artificial , Respiratory Insufficiency , Tracheostomy , Humans , Tracheostomy/statistics & numerical data , COVID-19/epidemiology , COVID-19/therapy , Male , Female , Retrospective Studies , Middle Aged , Respiratory Insufficiency/therapy , Patient Discharge/statistics & numerical data , Length of Stay/statistics & numerical data , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Aged , Intensive Care Units , APACHE , Time FactorsABSTRACT
BACKGROUND: Conflicting evidence exists evaluating associations between cannabis (THC) and post-traumatic DVT. METHODS: Retrospective analysis (2014-2023) of patients ≥15yrs from two Level I trauma centers with robust VTE surveillance and prophylaxis protocols. Multivariable hierarchical regression assessed the association between THC and DVT risk. THC â+ âpatients were direct matched to other drug use categories on VTE risk markers and hospital length of stay. RESULTS: Of 7365 patients, 3719 were drug-, 575 were THC â+ âonly, 2583 were other drug+, and 488 were TCH+/other drug+. DVT rates by exposure group did not differ. TCH â+ âonly patients had higher GCS scores, shorter hospital length of stay, and the lowest pelvic fracture and mortality rates. A total of 458 drug-, 453 other drug+, and 232 THC+/other drug â+ âpatients were matched to 458, 453, and 232 THC â+ âonly patients. There were no differences in DVT event rates in any paired sub-cohort set. Additionally, iteratively adjusted paired models did not show an association between THC and DVT. CONCLUSIONS: THC does not appear to be associated with increased DVT risk in patients with strict trauma chemoprophylaxis. Toxicology testing is useful for identifying substance abuse intervention opportunities, but not for DVT risk stratification in THC â+ âpatients.
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Venous Thromboembolism , Wounds and Injuries , Humans , Male , Female , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Middle Aged , Adult , Wounds and Injuries/complications , Risk Factors , Trauma Centers/statistics & numerical data , Cannabis/adverse effects , Aged , Risk Assessment , Length of Stay/statistics & numerical dataABSTRACT
ABSTRACT: Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.
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Blood Transfusion , Military Medicine , Humans , Military Medicine/methods , Blood Transfusion/methods , United States , Blood Banks , Wounds and Injuries/therapy , Military Personnel , War-Related Injuries/therapy , WarfareABSTRACT
Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These 'persister' cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.
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Acrylamides , Drug Resistance, Neoplasm , ErbB Receptors , Indoles , Lung Neoplasms , Mutation , Pyrimidines , Transcription Factors , Humans , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , ErbB Receptors/genetics , ErbB Receptors/metabolism , Drug Resistance, Neoplasm/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Cell Line, Tumor , Acrylamides/pharmacology , Acrylamides/therapeutic use , YAP-Signaling Proteins/metabolism , YAP-Signaling Proteins/genetics , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Gefitinib/pharmacology , Hippo Signaling Pathway , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Signal Transduction , TEA Domain Transcription Factors , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , Clustered Regularly Interspaced Short Palindromic Repeats , CRISPR-Cas SystemsABSTRACT
Introduction: Optimal venous thromboembolism (VTE) enoxaparin prophylaxis dosing remains elusive. Weight-based (WB) dosing safely increases anti-factor Xa levels without the need for routine monitoring but it is unclear if it leads to lower VTE risk. We hypothesized that WB dosing would decrease VTE risk compared with standard fixed dosing (SFD). Methods: Patients from the prospective, observational CLOTT-1 registry receiving prophylactic enoxaparin (n=5539) were categorized as WB (0.45-0.55 mg/kg two times per day) or SFD (30 mg two times per day, 40 mg once a day). Multivariate logistic regression was used to generate a predicted probability of VTE for WB and SFD patients. Results: Of 4360 patients analyzed, 1065 (24.4%) were WB and 3295 (75.6%) were SFD. WB patients were younger, female, more severely injured, and underwent major operation or major venous repair at a higher rate than individuals in the SFD group. Obesity was more common among the SFD group. Unadjusted VTE rates were comparable (WB 3.1% vs. SFD 3.9%; p=0.221). Early prophylaxis was associated with lower VTE rate (1.4% vs. 5.0%; p=0.001) and deep vein thrombosis (0.9% vs. 4.4%; p<0.001), but not pulmonary embolism (0.7% vs. 1.4%; p=0.259). After adjustment, VTE incidence did not differ by dosing strategy (adjusted OR (aOR) 0.75, 95% CI 0.38 to 1.48); however, early administration was associated with a significant reduction in VTE (aOR 0.47, 95% CI 0.30 to 0.74). Conclusion: In young trauma patients, WB prophylaxis is not associated with reduced VTE rate when compared with SFD. The timing of the initiation of chemoprophylaxis may be more important than the dosing strategy. Further studies need to evaluate these findings across a wider age and comorbidity spectrum. Level of evidence: Level IV, therapeutic/care management.