Weight-based enoxaparin thromboprophylaxis in young trauma patients: analysis of the CLOTT-1 registry.

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.

Management Patterns and Outcomes After Traumatic Brain Injury With Associated Blunt Cerebrovascular Injury.

BACKGROUND AND OBJECTIVES: Although blunt cerebrovascular injuries (BCVIs) are relatively common in patients with traumatic brain injuries (TBIs), uncertainty remains regarding optimal management strategies to prevent neurological complications, morbidity, and mortality. Our objectives were to characterize common care patterns; assess the prevalence of adverse outcomes, including stroke, functional deficits, and death, by BCVI grade; and evaluate therapeutic approaches to treatment in patients with BCVI and TBI. METHODS: Patients with TBI and BCVI treated at our Level I trauma center from January 2016 to December 2020 were identified. Presenting characteristics, treatment, and outcomes were captured for univariate and multivariate analyses. RESULTS: Of 323 patients with BCVI, 145 had Biffl grade I, 91 had grade II, 49 had grade III, and 38 had grade IV injuries. Lower-grade BCVIs were more frequently managed with low-dose (81 mg) aspirin ( P < .01), although all grades were predominantly treated with high-dose (150-600 mg) aspirin ( P = .10). Patients with low-grade BCVIs had significantly fewer complications ( P < .01) and strokes ( P < .01). Most strokes occurred in the acute time frame (<24 hours), including 10/11 (90.9%) grade IV-related strokes. Higher BCVI grade portended elevated risk of stroke (grade II odds ratio [OR] 5.3, grade III OR 12.2, and grade IV OR 19.6 compared with grade I; all P < .05). The use of low- or high-dose aspirin was protective against mortality (both OR 0.1, P < .05). CONCLUSION: In patients with TBI, BCVIs impart greater risk for stroke and other associated morbidities as their severity increases. It may prove difficult to mitigate high-grade BCVI-related stroke, considering most events occur in the acute window. The paucity of late time frame strokes suggest that current management strategies do help mitigate risks.

Characterizing re-triage guidelines: A scoping review of states' rules and regulations.

BACKGROUND: State guidelines for re-triage, or emergency inter-facility transfer, have never been characterized across the United States. METHODS: All 50 states' Department of Health and/or Trauma System websites were reviewed for publicly available re-triage guidelines within their rules and regulations. Communication was made via phone or email to state agencies or trauma advisory committees to obtain or confirm the absence of guidelines where public data was unavailable. Guideline criteria were abstracted and grouped into domains of Center for Disease Control Field Triage Criteria: pattern/anatomy of injury, vital signs, special populations, and mechanisms of injury. Re-triage criteria were summarized across states using median and interquartile ranges for continuous data and frequencies for categorical data. Demographic data of states with and without re-triage guidelines were compared using the Wilcoxon rank sum test. RESULTS: Re-triage guidelines were identified for 22 of 50 states (44%). Common anatomy of injury criteria included head trauma (91% of states with guidelines), spinal cord injury (82%), chest injury (77%), and pelvic injury (73%). Common vital signs criteria included Glasgow Coma Score (91% of states) ranging from 8 to 14, systolic blood pressure (36%) ranging from 90 to 100 mm Hg, and respiratory rate (23%) with all using 10 respirations/minute. Common special populations criteria included mechanical ventilation (73% of states), age (68%) ranging from <2 or >60 years, cardiac disease (59%), and pregnancy (55%). No significant demographic differences were found between states with versus without re-triage guidelines. CONCLUSION: A minority of US states have re-triage guidelines. Characterizing existing criteria can inform future guideline development.

Impact of premorbid oral anticoagulant use on survival in patients with traumatic intracranial hemorrhage.

OBJECTIVE: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation. METHODS: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis. RESULTS: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001). CONCLUSIONS: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

Prevalence and Risk Factors for Intensive Care Unit Delirium After Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Delirium remains understudied after traumatic brain injury (TBI). We sought to identify independent predictors of delirium among intensive care unit (ICU) patients with TBI. METHODS: This single-center retrospective cohort study evaluated adult patients with TBI requiring ICU admission. Outcomes included delirium days within the first 14 days, as assessed by the Confusion Assessment Method-ICU (CAM-ICU). Models were adjusted for age, sex, insurance, Marshall head computed tomography classification, presence of subarachnoid hemorrhage (SAH), Injury Severity Score (ISS), need for cardiopulmonary resuscitation, maximum admission Glasgow Coma motor score, glucose level, hemoglobin level, and pupil reactivity. RESULTS: Delirium prevalence was 60%, with a median duration of 4 days (interquartile range: 2-8) among ICU patients with TBI (n = 2,664). Older age, higher ISS, maximum motor score < 6, Marshall class II-IV, and SAH were associated with risk of increased delirium duration (all p < 0.001). CONCLUSIONS: In this large cohort, ICU delirium after TBI affected three of five patients for a median duration of 4 days. Age, general injury severity, motor score, and features of intracranial hemorrhage were predictive of more TBI-associated delirium days. Given the high prevalence of ICU delirium after TBI and its impact on hospitalization, further work is needed to understand the impact of delirium and TBI on outcomes and to determine whether delirium risk can be minimized.

Dynamic predictors of in-hospital and 3-year mortality after traumatic brain injury: A retrospective cohort study.

BACKGROUND: Mortality risks after Traumatic Brain Injury (TBI) are understudied in critical illness. We sought to identify risks of mortality in critically ill patients with TBI using time-varying covariates. METHODS: This single-center, six-year (2006-2012), retrospective cohort study measured demographics, injury characteristics, and daily data of acute TBI patients in the Intensive Care Unit (ICU). Time-varying Cox proportional hazards models assessed in-hospital and 3-year mortality. RESULTS: Post-TBI ICU patients (n = 2664) experienced 20% in-hospital mortality (n = 529) and 27% (n = 706) 3-year mortality. Glasgow Coma Scale motor subscore (hazard ratio (HR) 0.58, p < 0.001), pupil reactivity (HR 3.17, p < 0.001), minimum glucose (HR 1.44, p < 0.001), mSOFA score (HR 1.81, p < 0.001), coma (HR 2.26, p < 0.001), and benzodiazepines (HR 1.38, p < 0.001) were associated with in-hospital mortality. At three years, public insurance (HR 1.78, p = 0.011) and discharge disposition (HR 4.48, p < 0.001) were associated with death. CONCLUSIONS: Time-varying characteristics influenced in-hospital mortality post-TBI. Socioeconomic factors primarily affect three-year mortality.

Remote Oxygen Scavenging of the Interfacial Oxide Layer in Ferroelectric Hafnium-Zirconium Oxide-Based Metal-Oxide-Semiconductor Structures.

Discovery of ferroelectricity in HfO2 has sparked a lot of interest in its use in memory and logic due to its CMOS compatibility and scalability. Devices that use ferroelectric HfO2 are being investigated; for example, the ferroelectric field-effect transistor (FEFET) is one of the leading candidates for next generation memory technology, due to its area, energy efficiency and fast operation. In an FEFET, a ferroelectric layer is deposited on Si, with an SiO2 layer of ∼1 nm thickness inevitably forming at the interface. This interfacial layer (IL) increases the gate voltage required to switch the polarization and write into the memory device, thereby increasing the energy required to operate FEFETs, and makes the technology incompatible with logic circuits. In this work, it is shown that a Pt/Ti/thin TiN gate electrode in a ferroelectric Hf0.5Zr0.5O2 based metal-oxide-semiconductor (MOS) structure can remotely scavenge oxygen from the IL, thinning it down to ∼0.5 nm. This IL reduction significantly reduces the ferroelectric polarization switching voltage with a ∼2× concomitant increase in the remnant polarization and a ∼3× increase in the abruptness of polarization switching consistent with density functional theory (DFT) calculations modeling the role of the IL layer in the gate stack electrostatics. The large increase in remnant polarization and abruptness of polarization switching are consistent with the oxygen diffusion in the scavenging process reducing oxygen vacancies in the HZO layer, thereby depinning the polarization of some of the HZO grains.

Local Epitaxial Templating Effects in Ferroelectric and Antiferroelectric ZrO2.

Nanoscale polycrystalline thin-film heterostructures are central to microelectronics, for example, metals used as interconnects and high-K oxides used in dynamic random-access memories (DRAMs). The polycrystalline microstructure and overall functional response therein are often dominated by the underlying substrate or layer, which, however, is poorly understood due to the difficulty of characterizing microstructural correlations at a statistically meaningful scale. Here, an automated, high-throughput method, based on the nanobeam electron diffraction technique, is introduced to investigate orientational relations and correlations between crystallinity of materials in polycrystalline heterostructures over a length scale of microns, containing several hundred individual grains. This technique is employed to perform an atomic-scale investigation of the prevalent near-coincident site epitaxy in nanocrystalline ZrO2 heterostructures, the workhorse system in DRAM technology. The power of this analysis is demonstrated by answering a puzzling question: why does polycrystalline ZrO2 transform dramatically from being antiferroelectric on polycrystalline TiN/Si to ferroelectric on amorphous SiO2/Si?

Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial.

Balanced crystalloids may improve outcomes compared with saline for some critically ill adults. Lower tonicity of balanced crystalloids could worsen cerebral edema in patients with intracranial pathology. The effect of balanced crystalloids versus saline on clinical outcomes in patients with traumatic brain injury (TBI) requires further study. We planned an a priori subgroup analysis of TBI patients enrolled in the pragmatic, cluster-randomized, multiple-crossover Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (ClinicalTrials.gov: NCT02444988, NCT02547779). Primary outcome was 30-day in-hospital mortality. Secondary outcomes included hospital discharge disposition (home, facility, death). Regression models adjusted for pre-specified baseline covariates compared outcomes. TBI patients assigned to balanced crystalloids (n = 588) and saline (n = 569) had similar baseline characteristics including Injury Severity Score 19 (10); mean maximum head/neck Abbreviated Injury Score, 3.4 (1.0). Isotonic crystalloid volume administered between intensive care unit admission and first of hospital discharge or 30 days was 2037 (3470) mL and 1723 (2923) mL in the balanced crystalloids and saline groups, respectively (p = 0.18). During the study period, 94 (16%) and 82 (14%) patients (16%) died in the balanced crystalloid and saline groups, respectively (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.60 to 1.75; p = 0.913). Patients in the balanced crystalloid group were more likely to die or be discharged to another medical facility (aOR 1.38 [1.02-1.86]; p = 0.04). Overall, balanced crystalloids were associated with worse discharge disposition in critically injured patients with TBI compared with saline. The confidence intervals cannot exclude a clinically relevant increase in mortality when balanced crystalloids are used for patients with TBI.

Dexmedetomidine and paralytic exposure after damage control laparotomy: risk factors for delirium? Results from the EAST SLEEP-TIME multicenter trial.

PURPOSE: To evaluate factors associated with ICU delirium in patients who underwent damage control laparotomy (DCL), with the hypothesis that benzodiazepines and paralytic infusions would be associated with increased delirium risk. We also sought to evaluate the differences in sedation practices between trauma (T) and non-trauma (NT) patients. METHODS: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry admitted from January 1, 2017 to December 31, 2018. We included all adults undergoing DCL, regardless of diagnosis, who had completed daily Richmond Agitation Sedation Score (RASS) and Confusion Assessment Method-ICU (CAM-ICU). We excluded patients younger than 18 years, pregnant women, prisoners and patients who died before the first re-laparotomy. Data collected included age, number of re-laparotomies after DCL, duration of paralytic infusion, duration and type of sedative and opioid infusions as well as daily CAM-ICU and RASS scores to analyze risk factors associated with the proportion of delirium-free/coma-free ICU days during the first 30 days (DF/CF-ICU-30) using multivariate linear regression. RESULTS: A 353 patient subset (73.2% trauma) from the overall 567-patient cohort had complete daily RASS and CAM-ICU data. NT patients were older (58.9 ± 16.0 years vs 40.5 ± 17.0 years [p < 0.001]). Mean DF/CF-ICU-30 days was 73.7 ± 96.4% for the NT and 51.3 ± 38.7% in the T patients (p = 0.030). More T patients were exposed to Midazolam, 41.3% vs 20.3% (p = 0.002). More T patients were exposed to Propofol, 91.0% vs 71.9% (p < 0.001) with longer infusion times in T compared to NT (71.2 ± 85.9 vs 48.9 ± 69.8 h [p = 0.017]). Paralytic infusions were also used more in T compared to NT, 34.8% vs 18.2% (p < 0.001). Using linear regression, dexmedetomidine infusion and paralytic infusions were associated with decreases in DF/CF-ICU-30, (- 2.78 (95%CI [- 5.54, - 0.024], p = 0.040) and (- 7.08 ([- 13.0, - 1.10], p = 0.020) respectively. CONCLUSIONS: Although the relationship between paralytic use and delirium is well-established, the observation that dexmedetomidine exposure is independently associated with increased delirium and coma is novel and bears further study.

Time is domain: factors affecting primary fascial closure after trauma and non-trauma damage control laparotomy (data from the EAST SLEEP-TIME multicenter registry).

PURPOSE: Damage control laparotomy (DCL) is used for both traumatic and non-traumatic indications. Failure to achieve primary fascial closure (PFC) in a timely fashion has been associated with complications including sepsis, fistula, and mortality. We sought to identify factors associated with time to PFC in a multicenter retrospective cohort. METHODS: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry, including age, comorbidities (Charlson Comorbidity Index [CCI]), small and large bowel resection, bowel discontinuity, vascular procedures, retained packs, number of re-laparotomies, net fluid balance after 24 h, trauma, and time to first takeback in 12-h increments to identify key factors associated with time to PFC. RESULTS: In total, 368 patients (71.2% trauma, of which 50.6% were penetrating, median ISS 25 [16, 34], with median Apache II score 15 [11, 22] in non-trauma) were in the cohort. Of these, 92.9% of patients achieved PFC at 60.8 ± 72.0 h after 1.6 ± 1.2 re-laparotomies. Each additional re-laparotomy reduced the odds of PFC by 91.5% (95%CI 88.2-93.9%, p < 0.001). Time to first re-laparotomy was highly significant (p < 0.001) in terms of odds of achieving PFC, with no difference between 12 and 24 h to first re-laparotomy (ref), and decreases in odds of PFC of 78.4% (65.8-86.4%, p < 0.001) for first re-laparotomy after 24.1-36 h, 90.8% (84.7-94.4%, p < 0.001) for 36.1-48 h, and 98.1% (96.4-99.0%, p < 0.001) for > 48 h. Trauma patients had increased likelihood of PFC in two separate analyses (p = 0.022 and 0.002). CONCLUSION: Time to re-laparotomy ≤ 24 h and minimizing number of re-laparotomies are highly predictive of rapid achievement of PFC in patients after trauma- and non-trauma DCL. LEVEL OF EVIDENCE: 2B.

Trauma and nontrauma damage-control laparotomy: The difference is delirium (data from the Eastern Association for the Surgery of Trauma SLEEP-TIME multicenter trial).

BACKGROUND: Damage-control laparotomy (DCL) has been used for traumatic and nontraumatic indications. We studied factors associated with delirium and outcome in this population. METHODS: We reviewed DCL patients at 15 centers for 2 years, including demographics, Charlson Comorbidity Index (CCI), diagnosis, operations, and outcomes. We compared 30-day mortality; renal failure requiring dialysis; number of takebacks; hospital, ventilator, and intensive care unit (ICU) days; and delirium-free and coma-free proportion of the first 30 ICU days (DF/CF-ICU-30) between trauma (T) and nontrauma (NT) patients. We performed linear regression for DF/CF-ICU-30, including age, sex, CCI, achievement of primary fascial closure (PFC), small and large bowel resection, bowel discontinuity, abdominal vascular procedures, and trauma as covariates. We performed one-way analysis of variance for DF/CF-ICU-30 against traumatic brain injury severity as measured by Abbreviated Injury Scale for the head. RESULTS: Among 554 DCL patients (25.8% NT), NT patients were older (58.9 ± 15.8 vs. 39.7 ± 17.0 years, p < 0.001), more female (45.5% vs. 22.1%, p < 0.001), and had higher CCI (4.7 ± 3.3 vs. 1.1 ± 2.2, p < 0.001). The number of takebacks (1.7 ± 2.6 vs. 1.5 ± 1.2), time to first takeback (32.0 hours), duration of bowel discontinuity (47.0 hours), and time to PFC were similar (63.2 hours, achieved in 73.5%). Nontrauma and T patients had similar ventilator, ICU, and hospital days and mortality (31.0% NT, 29.8% T). Nontrauma patients had higher rates of renal failure requiring dialysis (36.6% vs. 14.1%, p < 0.001) and postoperative abdominal sepsis (40.1% vs. 17.1%, p < 0.001). Trauma and NT patients had similar number of hours of sedative (89.9 vs. 65.5 hours, p = 0.064) and opioid infusions (106.9 vs. 96.7 hours, p = 0.514), but T had lower DF/CF-ICU-30 (51.1% vs. 73.7%, p = 0.029), indicating more delirium. Linear regression analysis indicated that T was associated with a 32.1% decrease (95% CI, 14.6%-49.5%; p < 0.001) in DF/CF-ICU-30, while achieving PFC was associated with a 25.1% increase (95% CI, 10.2%-40.1%; p = 0.001) in DF/CFICU-30. Increasing Abbreviated Injury Scale for the head was associated with decreased DF/CF-ICU-30 by analysis of variance (p < 0.001). CONCLUSION: Nontrauma patients had higher incidence of postoperative abdominal sepsis and need for dialysis, while T was independently associated with increased delirium, perhaps because of traumatic brain injury. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Management and Challenges of Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients, and can be classified into mild, moderate, and severe by the Glasgow coma scale (GCS). Prehospital, initial emergency department, and subsequent intensive care unit (ICU) management of severe TBI should focus on avoiding secondary brain injury from hypotension and hypoxia, with appropriate reversal of anticoagulation and surgical evacuation of mass lesions as indicated. Utilizing principles based on the Monro-Kellie doctrine and cerebral perfusion pressure (CPP), a surrogate for cerebral blood flow (CBF) should be maintained by optimizing mean arterial pressure (MAP), through fluids and vasopressors, and/or decreasing intracranial pressure (ICP), through bedside maneuvers, sedation, hyperosmolar therapy, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or decompressive craniectomy (DC). While controversial, direct ICP monitoring, in conjunction with clinical examination and imaging as indicated, should help guide severe TBI therapy, although new modalities, such as brain tissue oxygen (PbtO2) monitoring, show great promise in providing strategies to optimize CBF. Optimization of the acute care of severe TBI should include recognition and treatment of paroxysmal sympathetic hyperactivity (PSH), early seizure prophylaxis, venous thromboembolism (VTE) prophylaxis, and nutrition optimization. Despite this, severe TBI remains a devastating injury and palliative care principles should be applied early. To better affect the challenging long-term outcomes of severe TBI, more and continued high quality research is required.

Adrenocorticotropin Hormone Secreting Carcinoma of the Pancreas: A Case Report.

Introduction: Adrenocorticotropin hormone (ACTH) secreting pancreatic neuroendocrine neoplasms (pNENs) are rare. The clinical and biological behavior of pNENs is poorly understood. Patients often present at an advanced stage of disease and outcomes remain poor. This report demonstrates a case of ectopic Cushing's syndrome secondary to an ACTH-producing pancreatic neuroendocrine carcinoma (pNEC). Case report: A 54-year-old woman presented with rapidly progressive Cushing's syndrome complicated by hypertension and acute heart failure. This was ultimately found to be secondary to a metastatic ACTH-producing pNEC. She underwent laparoscopic distal pancreatectomy and splenectomy with hepatic metastasectomy as primary treatment. She had rapid correction of her endocrine abnormalities and associated physiological abnormalities. She had progressive hepatic metastases found on imaging at 3 months, but remained free of significant endocrine abnormalities for 9 months after surgery. Her disease did recur and she died of complications associated with her disease at 1 year after her surgery. Conclusion: ACTH-producing pNEN is a very rare disease with a poor prognosis. Robust evidence to guide treatment decisions is limited. This report suggests that aggressive surgical management of primary and metastatic lesions for management of this disease is reasonable, consistent with prior case reports. Control of endocrine abnormalities offers the best opportunity for prolonged survival, and an aggressive surgical approach can achieve this goal. The patient presented had control of endocrine abnormalities after surgery for 9 months before symptomatic disease recurrence.

Cost and outcomes of open versus laparoscopic cholecystectomy in Mongolia.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for biliary disease in developed countries. LC in resource-limited countries is increasing. This prospective, observational study evaluates costs, outcomes, and quality of life (QoL) associated with laparoscopic versus open cholecystectomy (OC) in Mongolia. METHODS: Patient demographics, outcomes, and total payer and patient costs were elicited from a convenience sample of patients undergoing cholecystectomy at four urban and three rural hospitals (February 2016-January 2017). QoL was assessed preoperatively and postoperatively using the five-level EQ-5D instrument. Perioperative complications, surgical fees, and QoL scores were evaluated for LC versus OC. Multivariate regression models were generated to adjust for differences between these groups. RESULTS: Two hundred and fifteen cholecystectomies were included (LC 122, OC 93). LC patients were more likely to have attended college and have insurance. Preoperative symptoms were comparable between groups. Total complication rate was 21.8% (no difference between groups); LC patients had less superficial infections (0% versus 10.8%). Median hospital length of stay (HLOS) and days to return to work were shorter after LC. QoL improved after surgery for both groups. Mean total payer and patient costs were higher for LC, but not significant (P-value 0.126). After adjustment, LC had significantly less complications, shorter HLOS, fewer days to return to work, greater improvement in QoL scores, and no increase in cost. CONCLUSIONS: LC is safe and beneficial to patients with biliary disease in Mongolia, and cost effective from the patient's and payer's perspective. Although equipment costs for LC may be more expensive than OC, there are likely significant cost savings related to reduced HLOS, shorter time off work, fewer complications, and improved QoL.

Factor VIIa administration in traumatic brain injury: an AAST-MITC propensity score analysis.

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been used off-label as an adjunct in the reversal of warfarin therapy and management of hemorrhage after trauma. Only a handful of these reports are rigorous studies, from which results regarding safety and effectiveness have been mixed. There remains no clear consensus as to the role of rFVIIa in traumatic brain injury (TBI). METHODS: Eleven level 1 trauma centers provided clinical data and head CT scans of patients with a Glasgow Coma Scale (GCS) score of ≤13 and radiographic evidence of TBI. A propensity score (PS) to receive rFVIIa in those surviving ≥2 days was calculated for each patient based on patient demographics, comorbidities, physiology, Injury Severity Score, admission GCS score, and treatment center. Patients receiving rFVIIa within 24 hours of admission were matched to patients who did not receive rFVIIa for outcomes assessment. Subgroup analysis evaluated patients with primary head injury with PS matching. RESULTS: There were 4284 patient observations; 129 received rFVIIa. Groups were comparable after matching. No differences in mortality or morbidity were found. Improvement in GCS score from admission to discharge was less among those receiving rFVIIa (5.5 vs. 2.4; P value 0.001); however, there was no difference in average GCS score at discharge. No significant differences in outcomes were identified in patients with isolated TBI receiving rFVIIa. DISCUSSION: rFVIIa in early management of TBI is not associated with a decreased risk of mortality or morbidity, and may negatively impact recovery and functional status at discharge in the severely injured patient with polytrauma. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic/care management.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study.

BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Neuro, trauma, or med/surg intensive care unit: Does it matter where multiple injuries patients with traumatic brain injury are admitted? Secondary analysis of the American Association for the Surgery of Trauma Multi-Institutional Trials Committee decompressive craniectomy study.

INTRODUCTION: Patients with nontraumatic acute intracranial pathology benefit from neurointensivist care. Similarly, trauma patients with and without traumatic brain injury (TBI) fare better when treated by a dedicated trauma team. No study has yet evaluated the role of specialized neurocritical (NICU) and trauma intensive care units (TICU) in the management of TBI patients, and it remains unclear which TBI patients are best served in NICU, TICU, or general (Med/Surg) ICU. METHODS: This study is a secondary analysis of The American Association for the Surgery of Trauma Multi-Institutional Trials Committee (AAST-MITC) decompressive craniectomy study. Twelve Level 1 trauma centers provided clinical data and head computed tomography (CT) scans of patients with Glasgow Coma Scale score of 13 or less and CT evidence of TBI. Non-ICU admissions were excluded. Multivariate logistic regression was performed to measure the association between ICU type and survival and calculate the probability of death for increasing Injury Severity Score (ISS). Multiple injuries patients (ISS > 15) with TBI and isolated TBI patients (other Abbreviated Injury Scale score < 3) were analyzed separately. RESULTS: There were 3641 patients with CT evidence of TBI with 2951 admitted to an ICU. Before adjustment, patient demographics, injury severity, and survival differed significantly by unit type. After adjustment, unit type, age, and ISS remained independent predictors of death. Unit type modified the effect of ISS on mortality. TBI multiple injuries patients admitted to a TICU had improved survival across increasing ISS. Survival for isolated TBI patients was similar between TICU and NICU. Med/surg ICU carried the greatest probability of death. CONCLUSION: Multiple injuries patients with TBI have lower mortality risk when admitted to a trauma ICU. This survival benefit increases with increasing injury severity. Isolated TBI patients have similar mortality risk when admitted to a neuro ICU compared with a trauma ICU. Med/surg ICU admission carries the highest mortality risk. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Industry-academic partnerships: an approach to accelerate innovation.

BACKGROUND: Biotechnology companies are process-driven organizations and often struggle with their ability to innovate. Universities, on the other hand, thrive on discovery and variation as a source of innovation. As such, properly structured academic-industry partnerships in medical technology development may enhance and accelerate innovation. Through joint industry-academic efforts, our objective was to develop a technology aimed at global cervical cancer prevention. METHODS: Our Center for Medical Innovation assembled a multidisciplinary team of students, surgical residents, and clinical faculty to enter in the University of Utah's annual Bench-to-Bedside competition. Bench-to-Bedside is a university program centered on medical innovation. Teams are given access to university resources and are provided $500.00 for prototype development. Participation by team members are on a volunteer basis. Our industry partner presented the validated need and business mentorship. The team studied the therapeutic landscape, environmental constraints, and used simulation to understand human factors design and usage requirements. A physical device was manufactured by first creating a digital image (SOLIDWORKS 3D CAD). Then, using a 3-dimensional printer (Stratasys Objet30 Prime 3D printer), the image was translated into a physical object. Tissue burn depth analysis was performed on raw chicken breasts warmed to room temperature. Varying combinations of time and temperature were tested, and burn depth and diameter were measured 30 min after each trial. An arithmetic mean was calculated for each corresponding time and temperature combination. User comprehension of operation and sterilization was tested via a participant validation study. Clinical obstetricians and gynecologists were given explicit instructions on usage details and then asked to operate the device. Participant behaviors and questions were recorded. RESULTS: Our efforts resulted in a functional battery-powered hand-held thermocoagulation prototype in just 72 d. Total cost of development was <$500. Proof of concept trials at 100°C demonstrated an average ablated depth and diameter of 4.7 mm and 23.3 mm, respectively, corresponding to treatment efficacy of all grades of precancerous cervical lesions. User comprehension studies showed variable understanding with respect to operation and sterilization instructions. CONCLUSIONS: Our experience with using industry-academic partnerships as a means to create medical technologies resulted in the rapid production of a low-cost device that could potentially serve as an integral piece of the "screen-and-treat" approach to premalignant cervical lesions as outlined by World Health Organization. This case study highlights the impact of accelerating medical advances through industry-academic partnership that leverages their combined resources.

Should adhesive small bowel obstruction be managed laparoscopically? A National Surgical Quality Improvement Program propensity score analysis.

BACKGROUND: Celiotomy is the most common approach for refractory small bowel obstruction (SBO). Small reviews suggest that a laparoscopic approach is associated with shorter stay and less morbidity. Given the limitations of previous studies, we sought to evaluate outcomes of laparoscopic (L) compared with open (O) adhesiolysis for SBO, using the National Surgical Quality Improvement Program data set. METHODS: Patients from the American College of Surgeons' National Surgical Quality Improvement Program 2005 to 2009 database who underwent surgery for SBO were stratified based on surgical approach. A propensity score to undergo L instead of O was calculated based on demographics, comorbidities, physiology, and laboratory values. Logistic regression was then used to determine differences in outcomes between those propensity score-matched patients who actually underwent L compared with O surgery. RESULTS: There were 6,762 patients who underwent adhesiolysis. The propensity score-matching process created 222 matched patients in L and O groups. Laparoscopy was associated with significantly lower rates of any complication (odds ratio [OR] 0.41; 95% confidence interval [CI], 0.28-0.60), including superficial site infections (OR, 0.15; 95% CI, 0.05-0.49), intraoperative transfusion (OR, 0.22; 95% CI, 0.05-0.90), and shorter hospital stay (4 days vs. 10 days; p < 0.001). There was no significant difference in operative time, rates of reoperation within 30 days, or mortality. CONCLUSION: Laparoscopic treatment of SBO is associated with lower rates of postoperative morbidity compared with laparotomy as well as shorter hospital stay. Laparoscopic treatment of surgical SBO is not associated with higher rates of early reoperation and seems to be associated with lower resource use. LEVEL OF EVIDENCE: Therapeutic study, level IV.