Warfarin, not direct oral anticoagulants nor antiplatelet therapy, is associated with increased bleeding risk in emergency general surgery patients: implications in this new era of novel anticoagulants: An EAST Multicenter study.

INTRODUCTION: To assess perioperative bleeding complications & in-hospital mortality in patients requiring emergency general surgery (EGS) presenting with a history of antiplatelet (AP) vs. direct oral anticoagulant (DOAC) vs warfarin use. METHODS: Prospective observational study across 21 centers between 2019-2022. Inclusion criteria were age ≥ 18 years, & DOAC, warfarin or AP use within 24 hours of an EGSP. Outcomes included perioperative bleeding and in-hospital mortality. The study was conducted using ANOVA, Chi-square, and multivariable regression models. RESULTS: Of the 413 patients, 221 (53.5%) reported AP use, 152 (36.8%) DOAC use, & 40 (9.7%) warfarin use. Most common indications for surgery were obstruction (23% (AP), 45% (DOAC), 28% (warfarin)), intestinal ischemia (13%, 17%, 23%), & diverticulitis/peptic ulcers (7%, 7%, 15%). Compared to DOAC use, warfarin use was associated with significantly higher perioperative bleeding complication (OR 4.4 [2.0, 9.9]). There was no significant difference in perioperative bleeding complication between DOAC & AP use (OR 0.7 [0.4, 1.1]). Compared to DOAC use, there was no significant difference in mortality between warfarin use (0.7 [0.2, 2.5]) or AP use (OR 0.5 [0.2, 1.2]). After adjusting for confounders, warfarin use (OR 6.3 [2.8, 13.9]), medical history and operative indication were associated with an increase in perioperative bleeding complications. However, warfarin was not independently associated with risk of mortality (OR 1.3 [0.39, 4.7]), whereas intraoperative vasopressor use (OR 4.7 [1.7, 12.8)), medical history & postoperative bleeding (OR 5.5 [2.4, 12.8]) were. CONCLUSIONS: Despite ongoing concerns about the increase in DOAC use & lack of readily available reversal agents, this study suggests that warfarin, rather than DOACs, is associated with higher perioperative bleeding complications. However, that risk does not result in an increase in mortality, suggesting that perioperative decisions should be dictated by patient disease & comorbidities rather than type of antiplatelet or anticoagulant use.

Does lower extremity fracture fixation technique influence neurologic outcomes in patients with traumatic brain injury? The EAST Brain vs. Bone multicenter trial.

OBJECTIVE: This study aimed to determine whether lower extremity fracture fixation technique and timing (≤24 vs. >24 hours) impact neurologic outcomes in TBI patients. METHODS: A prospective observational study was conducted across 30 trauma centers. Inclusion criteria were age 18 years and older, head Abbreviated Injury Scale (AIS) score of >2, and a diaphyseal femur or tibia fracture requiring external fixation (Ex-Fix), intramedullary nailing (IMN), or open reduction and internal fixation (ORIF). The analysis was conducted using analysis of variamce, Kruskal-Wallis, and multivariable regression models. Neurologic outcomes were measured by discharge Ranchos Los Amigos Revised Scale (RLAS-R). RESULTS: Of the 520 patients enrolled, 358 underwent Ex-Fix, IMN, or ORIF as definitive management. Head AIS was similar among cohorts. The Ex-Fix group experienced more severe lower extremity injuries (AIS score, 4-5) compared with the IMN group (16% vs. 3%, p = 0.01) but not the ORIF group (16% vs. 6%, p = 0.1). Time to operative intervention varied between the cohorts with the longest time to intervention for the IMN group (median hours: Ex-Fix, 15 [8-24] vs. ORIF, 26 [12-85] vs. IMN, 31 [12-70]; p < 0.001). The discharge RLAS-R score distribution was similar across the groups. After adjusting for confounders, neither method nor timing of lower extremity fixation influenced the discharge RLAS-R. Instead, increasing age and head AIS score were associated with a lower discharge RLAS-R score (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002-1.03 and OR, 2.37; 95% CI, 1.75-3.22), and a higher Glasgow Coma Scale motor score on admission (OR, 0.84; 95% CI, 0.73-0.97) was associated with higher RLAS-R score at discharge. CONCLUSION: Neurologic outcomes in TBI are impacted by severity of the head injury and not the fracture fixation technique or timing. Therefore, the strategy of definitive fixation of lower extremity fractures should be dictated by patient physiology and the anatomy of the injured extremity and not by the concern for worsening neurologic outcomes in TBI patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Anticoagulation in emergency general surgery: Who bleeds more? The EAST multicenter trials ACES study.

BACKGROUND: While direct oral anticoagulant (DOAC) use is increasing in the Emergency General Surgery (EGS) patient population, our understanding of their bleeding risk in the acute setting remains limited. Therefore, the objective of this study was to determine the prevalence of perioperative bleeding complications in patients using DOACs versus warfarin and AP therapy requiring urgent/emergent EGS procedures (EGSPs). METHODS: This was a prospective observational trial, conducted between 2019 and 2022, across 21 centers. Inclusion criteria were 18 years or older, DOAC, warfarin/AP use within 24 hours of requiring an urgent/emergent EGSP. Demographics, preoperative, intraoperative, and postoperative data were collected. ANOVA, χ 2 , and multivariable regression models were used to conduct the analysis. RESULTS: Of the 413 patients enrolled in the study, 261 (63%) reported warfarin/AP use and 152 (37%) reported DOAC use. Appendicitis and cholecystitis were the most frequent indication for operative intervention in the warfarin/AP group (43.4% vs. 25%, p = 0.001). Small bowel obstruction/abdominal wall hernias were the main indication for operative intervention in the DOAC group (44.7% vs. 23.8%, p = 0.001). Intraoperative, postoperative, and perioperative bleeding complications and in-hospital mortality were similar between the two groups. After adjusting for confounders, a history of chemotherapy (odds ratio [OR], 4.3; p = 0.015) and indication for operative intervention including occlusive mesenteric ischemia (OR, 4.27; p = 0.016), nonocclusive mesenteric ischemia (OR, 3.13; p = 0.001), and diverticulitis (OR, 3.72; p = 0.019) were associated with increased perioperative bleeding complications. The need for an intraoperative transfusion (OR, 4.87; p < 0.001), and intraoperative vasopressors (OR, 4.35; p = 0.003) were associated with increased in-hospital mortality. CONCLUSION: Perioperative bleeding complications and mortality are impacted by the indication for EGSPs and patient's severity of illness rather than a history of DOAC or warfarin/AP use. Therefore, perioperative management should be guided by patient physiology and indication for surgery rather than the concern for recent antiplatelet or anticoagulant use. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Low Prevalence but High Impact of COVID-19 Positive Status in Adult Trauma Patients: A Multi-institutional Analysis of 28 904 Patients.

BACKGROUND: Few large investigations have addressed the prevalence of COVID-19 infection among trauma patients and impact on providers. The purpose of this study was to quantify the prevalence of COVID-19 infection among trauma patients by timing of diagnosis, assess nosocomial exposure risk, and evaluate the impact of COVID-19 positive status on morbidity and mortality. METHODS: Registry data from adults admitted 4/1/2020-10/31/2020 from 46 level I/II trauma centers were grouped by: timing of first positive status (Day 1, Day 2-6, or Day ≥ 7); overall Positive/Negative status; or Unknown if test results were unavailable. Groups were compared on outcomes (Trauma Quality Improvement Program complications) and mortality using univariate analysis and adjusted logistic regression. RESULTS: There were 28 904 patients (60.7% male, mean age: 56.4, mean injury severity score: 10.5). Of 13 274 (46%) patients with known COVID-19 status, 266 (2%) were Positive Day 1, 119 (1%) Days 2-6, 33 (.2%) Day ≥ 7, and 12 856 (97%) tested Negative. COVID-19 Positive patients had significantly worse outcomes compared to Negative; unadjusted comparisons showed longer hospital length of stay (10.98 vs 7.47;P < .05), higher rates of intensive care unit (57.7% vs 45.7%; P < .05) and ventilation use (22.5% vs 16.9%; P < .05). Adjusted comparisons showed higher rates of acute respiratory distress syndrome (1.7% vs .4%; P < .05) and death (8.1% vs 3.4%; P < .05). CONCLUSIONS: This multicenter study conducted during the early pandemic period revealed few trauma patients tested COVID-19 positive, suggesting relatively low exposure risk to care providers. COVID-19 positive status was associated with significantly higher mortality and specific morbidity. Further analysis is needed with consideration for care guidelines specific to COVID-19 positive trauma patients as the pandemic continues.

Where to Draw the Line for Intracranial Hypertension; Opening Pressures and Mortality.

BACKGROUND: Intracranial pressure (ICP) monitoring and treatment is a mainstay of severe TBI management but the relationship between intracranial opening pressure (OP) and outcomes has not been well established. The purpose of our study was to assess the relationship between OP and outcomes in severe TBI patients, with a focus on in-hospital mortality. METHODS: Adult blunt TBI patients with ICP monitoring between 2007 and 2017 were evaluated using sequential multivariable binary logistic modeling. Generalized additive model (GAM) was used to evaluate the relationship between OP and death. Odds ratio (OR) and 95% confidence interval (CI) were calculated for measures of strength of association and precision. RESULTS: A total of 182 patients were identified, with 61 (33.5%) having OP >20 mmHG (overall mean ± OP = 19.4 ± 17.8 mmHG). Forty-eight percent, 9% and 8% of patients were discharged to rehabilitation, skilled nursing institution, and home, respectively. Thirty-five percent died in the hospital. A linear relationship was found between OP and log-odds of mortality. OP (OR = 1.07; 95% CI = 1.04-1.11), age (OR = 1.05;95%CI = 1.02-1.07), and injury severity score (ISS) (OR = 1.06; 95% CI = 1.02-1.10) were independently associated with increased odds of death while adjusting for sex, race, and year. DISCUSSION: Elevated opening pressure is strongly predictive of death in severe TBI. Age and ISS are independent predictors of mortality regardless of OP. These results suggest that maintaining low levels of ICP should result in decreased mortality in severe TBI patients. The patient's age and ISS should be considered in the decision-making processes related to ICP utilization and management.

The public health burden of geriatric trauma: Analysis of 2,688,008 hospitalizations from Centers for Medicare and Medicaid Services inpatient claims.

BACKGROUND: Geriatric trauma care (GTC) represents an increasing proportion of injury care, but associated public health research on outcomes and expenditures is limited. The purpose of this study was to describe GTC characteristics, location, diagnoses, and expenditures. METHODS: Patients at short-term nonfederal hospitals, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision, were selected from 2016 to 2019 Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files. Trauma center levels were linked to Inpatient Standard Analytical Files data via American Hospital Association Hospital ID and fuzzy string matching. Demographics, care location, diagnoses, and expenditures were compared across groups. RESULTS: A total of 2,688,008 hospitalizations (62% female; 90% White; 71% falls; mean Injury Severity Score, 6.5) from 3,286 hospitals were included, comprising 8.5% of all Medicare inpatient hospitalizations. Level I centers encompassed 7.2% of the institutions (n = 236) but 21.2% of hospitalizations, while nontrauma centers represented 58.5% of institutions (n = 1,923) and 37.7% of hospitalizations. Compared with nontrauma centers, patients at Level I centers had higher Elixhauser scores (9.0 vs. 8.8) and Injury Severity Score (7.4 vs. 6.0; p < 0.0001). The most frequent primary diagnosis at all centers was hip/femur fracture (28.3%), followed by traumatic brain injury (10.1%). Expenditures totaled $32.9 billion for trauma-related hospitalizations, or 9.1% of total Medicare hospitalization expenditures and approximately 1.1% of the annual Medicare budget. The overall mortality rate was 3.5%. CONCLUSION: Geriatric trauma care accounts for 8.5% of all inpatient GTC and a similar percentage of expenditures, the most common injury being hip/femur fractures. The largest proportion of GTC occurs at nontrauma centers, emphasizing their vital role in trauma care. Public health prevention programs and GTC guidelines should be implemented by all hospitals, not just trauma centers. Further research is required to determine the optimal role of trauma systems in GTC, establish data-driven triage guidelines, and define the impact of trauma centers and nontrauma centers on GTC mortality. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

Thromboelastography Utilization in Delayed Recurrent Coagulopathy after Severe Eastern Diamondback Rattlesnake Envenomation.

Venomous snakebites are fairly common in the United States and can present with a wide range of symptoms. A 48-year-old man presented after Eastern Diamondback rattlesnake envenomation. His hospital course was complicated by right leg compartment syndrome and delayed recurrent coagulopathy, requiring multiple doses of Crotalidae Polyvalent Immune Fab (CroFab) antivenom and transfusions. Thromboelastography was used as an adjunct to standard coagulation studies in monitoring his delayed recurrent coagulopathy.

What's in the Box? The Effectiveness of a Low-Volume Massive Transfusion Protocol.

Transfusion ratios approaching 1:1:1 of packed red blood cells (PRBCs) to fresh frozen plasma (FFP) to platelet have been shown to improve outcomes in trauma. There is little data available to describe in what quantity that ratio should be delivered. We hypothesized that lowering the total volume of products delivered in each protocol round would not adversely affect outcomes in the bleeding trauma patient. A retrospective review of 9732 trauma patients admitted to a rural Level I trauma center over a 3-year period was performed. Patients who received a massive transfusion (greater than 10 units of blood product transfused in the first 24 hours), between January 2012 and April 2015 were identified as the study cohort. In May of 2014, our institution switched from a massive transfusion protocol (MTP) that included 6 PRBCs:6 FFP:1 platelet to a lower volume massive transfusion protocol (LVMTP) that included 4 PRBC:4 FFP:1 platelet. Data collected included patient demographics, vital signs, and outcomes. A total of 131 patients met study criteria. MTP was activated on 65 per cent of patients (57/88), receiving a massive transfusion during the 28 months before implementation of the new protocol. In contrast, LVMTP was activated in 100 per cent of patients (43/43) receiving a massive transfusion in the 12 months after implementation of the new protocol. There was no significant difference in age (36.6 vs 37.2, P = 0.87), injury severity score (29.8 vs 32.3, P = 0.45), or per cent penetrating mechanism (43.9 vs 37.2%, P = 0.503) when comparing MTP to LVMTP. In addition, there was no significant difference in mortality (47.4 vs 41.9%, P = 0.584), lengths of stay (13.5 vs 17.1, P = 0.258), or vent days (6.4 vs 8.2, P = 0.236) when comparing MTP to LVMTP. A LVMTP is safe and effective for the resuscitation of the trauma patient.

Sugar-derived organogels as templates for structured, photoluminescent conjugated polymer-inorganic hybrid materials.

Co-assembly of an inorganic-organic hybrid material through the combination of supramolecular organogel self-assembly, phase partitioning of a conjugated polymer (CP) and transcription of an inorganic oxide leads to a hybrid material with structured domains of organogel, CP and silica within tube and rod microstructures.

Improved survival of patients with pseudomyxoma peritonei receiving intraperitoneal chemotherapy with cytoreductive surgery: a systematic review and meta-analysis.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon but lethal variant of adenocarcinoma. Many recent case series have reported improved survival with the combination of cytoreductive surgery and intraperitoneal chemotherapy (IPEC) in treating PMP. The aim of this study was to analyze the published studies for improved survival with this treatment strategy. METHODS: Data from all studies using IPEC in treating PMP were analyzed. We searched PubMed, MEDLINE, and the Cochrane Library (through September 2011). Studies were limited to English and PMP with appendiceal origin. Twenty-nine studies were identified, with 15 studies from different treatment centers that were specifically analyzed for differences in 5-y mortality and morbidity. Observed to expected (OE) ratios were calculated for both mortality and morbidity. RESULTS: Mean and median 3-y, 5-y, and 10-y survival rates were 77.18%/77.85%, 76.63%/79.5%, and 57.3%/55.9%, respectively. Of the 10 studies that had sufficient data to calculate OE ratios from the 5-year mortality data, two had OE ratios lower than 1. Of the 11 studies that had data sufficient to calculate OE ratios from the morbidity data, four had OE ratios that were less than 1. CONCLUSIONS: Combining cytoreductive surgery and IPEC improves the survival of patients with PMP, regardless of treatment modality. Although this treatment strategy is associated with an increased risk of morbidity, the increase in survival may be acceptable in proposing an alternative to debulking procedures alone.

Sea urchin embryos exposed to thalidomide during early cleavage exhibit abnormal morphogenesis later in development.

BACKGROUND: Clinical use of thalidomide has increased drastically, pushing the questions concerning the teratogenic mechanisms of this drug back to the forefront. Progress in understanding the teratogenic mechanisms has been slow, with the lack of non-primate vertebrate animal models susceptible to the classic reduction deformities remaining a concern. Sea urchin embryos have been used as model organisms for developmental studies for the last century. Like vertebrates, they are deuterostomes and share similar developmental and signaling pathways suggesting they may be an effective system for thalidomide studies. Therefore, we tested sea urchin embryos to see if they were sensitive to the effects of thalidomide. METHODS: Sea urchin embryos were obtained using standard spawning and fertilization techniques. Thalidomide dissolved in DMSO was added to embryo cultures either at fertilization or during early cleavage. Samples of the embryos were evaluated during specific development stages. RESULTS: Lytechinus pictus embryos exposed to 400 microM thalidomide at fertilization or within a window during early cleavage (2-6 hours post-fertilization) exhibit significant levels of abnormal embryos (60-82%) at the pluteus stage, compared to controls levels (< or =10%). Strongylocentrotus purpuratus embryos exposed at initial fertilization or during early cleavage (2-6 hours post-fertilization) exhibit similar responses with significant abnormal levels ranging from (55-70%) at pluteus stage. CONCLUSIONS: Both species of sea urchin tested were susceptible to thalidomide-induced teratogenesis during cleavage (4-16 cell stages). This response during cleavage stages warrants further study and indicates that sea urchin embryos may prove to be a useful tool for studying thalidomide effects early in development.

Chemical composition of seminal and ovarian fluids of chinook salmon (Oncorhynchus tshawytscha) and their effects on sperm motility traits.

The relationships between the compositions of ovarian, seminal fluids and sperm function are not well known in teleostean fish species. The objective of the present study was to determine the concentration of the major inorganic ions (Na(+), K(+), Ca(2+), Mg, Cl(-)), osmolality, and pH of ovarian and seminal fluid of sexually mature chinook salmon (Oncorhynchus tshawytscha), and to determine if the composition of these fluids influences sperm motility traits (swimming speed, duration of forward mobility, swimming path trajectory, and percent motility). Cation concentrations and osmolality were significantly different in the two fluids. The ionic composition of ovarian fluid differed among individual females, and also among samples collected at different times through the spawning season. Carbonate and bicarbonate were the principal buffer ions in ovarian fluid, and its viscosity was considerably greater than that of water and was shear-dependent. The duration of forward motility (longevity) of spermatozoa, swimming speed, percent motility, and path trajectory were measured using milt from 10 males activated in the ovarian fluid from 7 females whose ion concentrations were known. No significant correlations were observed between the composition of the seminal fluid and sperm traits. However, in ovarian fluid, sperm longevity was negatively correlated with variation in [Ca(2+)] and [Mg(2+)], while percent motility increased with increasing [Mg(2+)]. These observations provide a possible chemical basis for cryptic female mate choice whereby female ovarian fluid differentially influences the behaviour of sperm from different males, and thus their fertilization success.

Perceived barriers to health care access in a treated population.

OBJECTIVE: Health care access may be a significant contributor to health outcome. However, few data exist on perception of barriers by patients in treatment, and attending a clinic visit does not mean that no barriers exist. Understanding barriers for treated populations is particularly important in optimizing care for high vulnerability populations, such as those with mental illness and the elderly. METHOD: A structured interview, demographic questionnaire, and SF-12 were administered to 324 veterans presenting for primary care or mental health appointments at a Veterans Affairs medical center. Principle components analysis was performed and relationships to vulnerability characteristics were identified. RESULTS: Most interview items showed modest mean levels but high variance. Responses were stable over three to six weeks. As hypothesized, perceived total barriers were greater in participants from several vulnerable populations: those receiving treatment for mental health problems, those with disabilities, and those with worse physical and mental function. Minority participants did not perceive greater barriers. An "inverted-U" relationship with age was found. Principal components analysis assigned 18 items across six clinically meaningful subscales. Participants with mental health treatment perceived greater barriers in three subscales including provider communication. Curvilinear relationships were again seen between subscales and age. CONCLUSIONS: Even individuals "in care" perceive barriers. Members of vulnerable populations, particularly those receiving mental health treatment, perceive greater barriers. Data support a multi-dimensional conceptualization of perceived barriers, and different subgroups experience different patterns of barriers.