Defining Risk and Risk Factors for Unplanned ICU Admission of Trauma Patients.

BACKGROUND: Unplanned ICU admissions (up-ICUad) are associated with poor outcomes. It is difficult to identify who is at risk for up-ICUad in trauma patients. This study aimed to identify injury patterns and comorbidities associated with up-ICUad and develop a predictive tool for who is at risk. METHODS: A retrospective study compared trauma patients admitted to the floor who experienced an up-ICUad to similar patients without an up-ICUad. Univariate analysis and multivariate logistic regression identified independent risk factors associated with up-ICUad. Based on those factors, a Risk Score (RS) was created and compared between the two groups. RESULTS: 2.15% of the 7206 patients experienced an up-ICUad. The up-ICUad group was older, experienced longer length of stay, and had higher mortality. Age, congestive heart failure, COPD, peptic ulcer disease, mild liver disease, CKD, and significant injuries to the thorax, spine, and lower extremities were independently associated with up-ICUad. A RS equation was created and was used for each patient. CONCLUSIONS: Trauma patients are at increased risk for up-ICUad based on specific factors. These factors can be used to calculate a RS to determine who is at greatest risk for an up-ICUad which may be helpful for preventing up-ICUad.

UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic.

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm-2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 µWcm-2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.

Artificial Intelligence, Machine Learning, and Surgical Science: Reality Versus Hype.

Artificial intelligence (AI) has made increasing inroads in clinical medicine. In surgery, machine learning-based algorithms are being studied for use as decision aids in risk prediction and even for intraoperative applications, including image recognition and video analysis. While AI has great promise in surgery, these algorithms come with a series of potential pitfalls that cannot be ignored as hospital systems and surgeons consider implementing these technologies. The aim of this review is to discuss the progress, promise, and pitfalls of AI in surgery.

Delay in ICU transfer is protective against ICU readmission in trauma patients: a naturally controlled experiment.

BACKGROUND: Unplanned intensive care unit (ICU) readmission-ICU bounce back (ICUbb)-is associated with worse outcomes. Patients not requiring organ system support or intensive nursing are deemed 'ICU discharge ready' and transfer orders are placed. However, actual transfer only occurs when an appropriate, non-ICU bed is available. This is dependent on inherent system inefficiencies resulting in a naturally controlled experiment between when patients actually transfer: Early (<24 hours) or Delayed (>24 hours) transfers, after order placement. This study leverages that natural experiment to determine if additional ICU time is protective against ICUbb. We hypothesize that Delayed transfer is protective against ICUbb. METHODS: Using a retrospective, cohort design, we queried a trauma research repository and electronic medical record during a 10-year period to capture traumatized patients admitted to the ICU. Patients were categorized into Early (<24 hours) or Unintended-Delayed (>24 hours) groups based on actual transfer time after order placement. Patient characteristics (age, Charlson Comorbidity Index (CCI)) and Injury Severity Score (ISS) were analyzed. Univariate and multivariate analyses were performed to compare ICUbb rates among Early and Unintended-Delayed groups. RESULTS: Of the 2004 patients who met the criteria, 1690 fell into the Early group, and 314 fell into the Delayed. The Early group was younger (mean age 52±23 vs. 55±22 years), had fewer comorbidities (median CCI score 1 (0, 3) vs. 2 (1, 3)), and was less injured (median ISS 17 (10-22) vs. 17 (13-25)), all p<0.05. Overall, 113 (5.6%) patients experienced ICUbb: Early 109 (6.5%) versus Unintended-Delay 4 (1.3%), p<0.05. By regression analysis, age, CCI, and ISS were independently associated with ICUbb while Delayed transfer was protective. DISCUSSION: Despite higher age, CCI score, and ISS, the Unintended-Delayed group experienced fewer ICUbb. After controlling for age, CCI and ISS, Delayed transfer reduced ICUbb risk by 78%. Specific care elements affording this protection remain to be elucidated. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic study.

Monitoring Perioperative Services Using 3D Multi-Objective Performance Frontiers.

The Acute Care Surgery model has been widely adopted by hospitals across the United States, with Acute Care Surgery services managing Emergency General Surgery patients that were previously being treated by General Surgery. In this analysis, we evaluate the impact of an Acute Care Surgery service model on General Surgery at the University of Vermont Medical Center using three metrics: under-utilized time, spillover time, and a financial ratio of work Relative Value Units over clinical Full Time Equivalents. These metrics are evaluated and used to identify three-dimensional Pareto optimality of General Surgery prior to and after the October 2015 tactical allocation to the Acute Care Surgery model. Our analysis was further substantiated using a Markov Chain Monte Carlo model for Bayesian Inference. We applied multi-objective Pareto and Bayesian breakpoint analysis to three operating room metrics to assess the impact of new operating room management decisions. In the two-dimensional space of Fig. 2, panel a), the post-tactical allocation front lies closer to the origin representing more optimal solutions for productivity and under-utilized time. The post-tactical allocation front is also closer to the origin for productivity and spillover time as shown in the two-dimensional space of Fig. 2, panel b). The results of the three-dimensional multi-objective analysis of Fig. 3 illustrate that the GS post-tactical allocation Pareto-surface is contained within a much smaller volume of space than the GS pre-tactical allocation Pareto-surface. The post-tactical allocation Pareto-surface is slightly lower along the z-axis, representing lower productivity than the pre-tactical allocation surface. This methodology might contribute to the external benchmarking and monitoring of perioperative services by visualizing the operational implications following tactical decisions in operating room management.

Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility.

Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis (UC) patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self-emptying (SEL) ileal loops using wild-type (WT), IL-10 knockout (KO) (IL-10), TLR4 KO (T4), and IL-10/T4 double KO mice. After 5 wk, loop histology, host gene/protein expression, and bacterial 16s rRNA profiles were examined. SFL exhibit fecal stasis due to directional motility oriented toward the loop end, whereas SEL remain empty. In WT mice, SFL, but not SEL, develop pouchlike microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. The inflammation associated with IL-10 required TLR4, as animals lacking both pathways displayed little disease. Furthermore, germ-free IL-10 mice conventionalized with SFL, but not SEL, microbiota populations develop severe colitis. These data support essential roles of stasis-induced, colon-like microbiota, TLR4-mediated colonic metaplasia, and genetic susceptibility in the development of pouchitis and possibly UC. However, these factors by themselves are not sufficient. Similarities between this model and human UC/pouchitis provide opportunities for gaining insights into the mechanistic basis of IBD and for identification of targets for novel preventative and therapeutic interventions.

Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4-5, 2012.

OBJECTIVE: The first international summit on anastomotic leak was held in Chicago in October, 2012 to assess current knowledge in the field and develop novel lines of inquiry. The following report is a summary of the proceedings with commentaries and future prospects for clinical trials and laboratory investigations. BACKGROUND: Anastomotic leakage remains a devastating problem for the patient, and a continuing challenge to the surgeon operating on high-risk areas of the gastrointestinal tract such as the esophagus and rectum. Despite the traditional wisdom that anastomotic leak is because of technique, evidence to support this is weak-to-non-existent. Outcome data continue to demonstrate that expert high-volume surgeons working in high-volume centers continue to experience anastomotic leaks and that surgeons cannot predict reliably which patients will leak. METHODS: A one and one-half day summit was held and a small working group assembled to review current practices, opinions, scientific evidence, and potential paths forward to understand and decrease the incidence of anastomotic leak. RESULTS: RESULTS of a survey of the opinions of the group demonstrated that the majority of participants believe that anastomotic leak is a complicated biologic problem whose pathogenesis remains ill-defined. The group opined that anastomotic leak is underreported clinically, it is not because of technique except when there is gross inattention to it, and that results from animal models are mostly irrelevant to the human condition. CONCLUSIONS: A fresh and unbiased examination of the causes and strategies for prevention of anastomotic leak needs to be addressed by a continuous working group of surgeons, basic scientists, and clinical trialists to realize a real and significant reduction in its incidence and morbidity. Such a path forward is discussed.

A case report of thoracic compartment syndrome in the setting of penetrating chest trauma and review of the literature.

Trauma-related thoracic compartment syndrome (TCS) is a rare, life threatening condition that develops secondary to elevated intra-thoracic pressure and manifests itself clinically as significantly elevated airway pressures, inability to provide adequate ventilation and hemodynamic instability temporally related to closure of a thoracic surgical incision. TCS is exceedingly rare in the trauma population. We present a case of TCS following surgical repair of a stab wound injury that necessitated decompressive thoracotomy and peri-operative open-chest management.

Translational systems biology using an agent-based approach for dynamic knowledge representation: An evolutionary paradigm for biomedical research.

The greatest challenge facing the biomedical research community is the effective translation of basic mechanistic knowledge into clinically effective therapeutics. This challenge is most evident in attempts to understand and modulate "systems" processes/disorders, such as sepsis, cancer, and wound healing. Formulating an investigatory strategy for these issues requires the recognition that these are dynamic processes. Representation of the dynamic behavior of biological systems can aid in the investigation of complex pathophysiological processes by augmenting existing discovery procedures by integrating disparate information sources and knowledge. This approach is termed Translational Systems Biology. Focusing on the development of computational models capturing the behavior of mechanistic hypotheses provides a tool that bridges gaps in the understanding of a disease process by visualizing "thought experiments" to fill those gaps. Agent-based modeling is a computational method particularly well suited to the translation of mechanistic knowledge into a computational framework. Utilizing agent-based models as a means of dynamic hypothesis representation will be a vital means of describing, communicating, and integrating community-wide knowledge. The transparent representation of hypotheses in this dynamic fashion can form the basis of "knowledge ecologies," where selection between competing hypotheses will apply an evolutionary paradigm to the development of community knowledge.

Detailed qualitative dynamic knowledge representation using a BioNetGen model of TLR-4 signaling and preconditioning.

INTRODUCTION: Intracellular signaling/synthetic pathways are being increasingly extensively characterized. However, while these pathways can be displayed in static diagrams, in reality they exist with a degree of dynamic complexity that is responsible for heterogeneous cellular behavior. Multiple parallel pathways exist and interact concurrently, limiting the ability to integrate the various identified mechanisms into a cohesive whole. Computational methods have been suggested as a means of concatenating this knowledge to aid in the understanding of overall system dynamics. Since the eventual goal of biomedical research is the identification and development of therapeutic modalities, computational representation must have sufficient detail to facilitate this 'engineering' process. Adding to the challenge, this type of representation must occur in a perpetual state of incomplete knowledge. We present a modeling approach to address this challenge that is both detailed and qualitative. This approach is termed 'dynamic knowledge representation,' and is intended to be an integrated component of the iterative cycle of scientific discovery. METHODS: BioNetGen (BNG), a software platform for modeling intracellular signaling pathways, was used to model the toll-like receptor 4 (TLR-4) signal transduction cascade. The informational basis of the model was a series of reference papers on modulation of (TLR-4) signaling, and some specific primary research papers to aid in the characterization of specific mechanistic steps in the pathway. This model was detailed with respect to the components of the pathway represented, but qualitative with respect to the specific reaction coefficients utilized to execute the reactions. Responsiveness to simulated lipopolysaccharide (LPS) administration was measured by tumor necrosis factor (TNF) production. Simulation runs included evaluation of initial dose-dependent response to LPS administration at 10, 100, 1000 and 10,000, and a subsequent examination of preconditioning behavior with increasing LPS at 10, 100, 1000 and 10,000 and a secondary dose of LPS at 10,000 administered at approximately 27h of simulated time. Simulations of 'knockout' versions of the model allowed further examination of the interactions within the signaling cascade. RESULTS: The model demonstrated a dose-dependent TNF response curve to increasing stimulus by LPS. Preconditioning simulations demonstrated a similar dose-dependency of preconditioning doses leading to attenuation of response to subsequent LPS challenge - a 'tolerance' dynamic. These responses match dynamics reported in the literature. Furthermore, the simulated 'knockout' results suggested the existence and need for dual negative feedback control mechanisms, represented by the zinc ring-finger protein A20 and inhibitor kappa B proteins (IkappaB), in order for both effective attenuation of the initial stimulus signal and subsequent preconditioned 'tolerant' behavior. CONCLUSIONS: We present an example of detailed, qualitative dynamic knowledge representation using the TLR-4 signaling pathway, its control mechanisms and overall behavior with respect to preconditioning. The intent of this approach is to demonstrate a method of translating the extensive mechanistic knowledge being generated at the basic science level into an executable framework that can provide a means of 'conceptual model verification.' This allows for both the 'checking' of the dynamic consequences of a mechanistic hypothesis and the creation of a modular component of an overall model directed at the engineering goal of biomedical research. It is hoped that this paper will increase the use of knowledge representation and communication in this fashion, and facilitate the concatenation and integration of community-wide knowledge.

Even ephemeral endotoxin exposure establishes endotoxin tolerance.

BACKGROUND: Macrophages previously exposed to bacterial lipopolysaccharide (LPS) develop a "tolerant" response with decreased extracellular signal-regulated kinase (ERK) activation in response to LPS rechallenge. Prior work using 21-hour LPS pretreatment showed that 100 ng/mL of LPS-inhibited tumor necrosis factor (TNF) release, whereas very low dose LPS (1 ng/mL) augmented TNF release. Endotoxin tolerance was also associated with alterations in activation of ERK and p38 kinase when cells were restimulated with LPS. We hypothesized that the interval after pretreatment, before LPS rechallenge, modulates macrophage response to LPS. METHODS: RAW 264.7 macrophage-like cells were pretreated for 4 hours in 0 ng/mL (none), 1 ng/mL, 10 ng/mL, or 100 ng/mL of Escherichia coli 0111:B4 LPS. After 4 hour pretreatment, medium was discarded. Cells were rechallenged immediately or 21 hours later with 0 ng/mL, 1 ng/mL, 10 ng/mL, or 100 ng/mL LPS. Supernatant TNF secretion at 3 hour was measured using enzyme-linked immunosorbent assay. Active phospho-ERK was examined by Western blot using specific monoclonal antibodies 30 minutes after LPS rechallenge. Statistical analysis by chi and student's t test. RESULTS: When macrophages were pretreated for 4 hour and incubated overnight (21-hour interval) 1 ng/mL of LPS augmented and 100 ng/mL inhibited TNF release with LPS rechallenge. In contrast, with immediate rechallenge, we saw additive effects with 100 ng/mL LPS and no difference with 1 ng/mL LPS versus no pretreatment. Western blot revealed that even with immediate rechallenge "tolerant" macrophages were unable to activate ERK. CONCLUSIONS: A short LPS exposure is sufficient to induce alterations in ERK activation in macrophages, but longer intervals are required to express altered cytokine release. In conjunction with other recent findings, these results suggest that both pretreatment dose and interval modulate macrophage responsiveness to LPS rechallenge.

The Basic Immune Simulator: an agent-based model to study the interactions between innate and adaptive immunity.

BACKGROUND: We introduce the Basic Immune Simulator (BIS), an agent-based model created to study the interactions between the cells of the innate and adaptive immune system. Innate immunity, the initial host response to a pathogen, generally precedes adaptive immunity, which generates immune memory for an antigen. The BIS simulates basic cell types, mediators and antibodies, and consists of three virtual spaces representing parenchymal tissue, secondary lymphoid tissue and the lymphatic/humoral circulation. The BIS includes a Graphical User Interface (GUI) to facilitate its use as an educational and research tool. RESULTS: The BIS was used to qualitatively examine the innate and adaptive interactions of the immune response to a viral infection. Calibration was accomplished via a parameter sweep of initial agent population size, and comparison of simulation patterns to those reported in the basic science literature. The BIS demonstrated that the degree of the initial innate response was a crucial determinant for an appropriate adaptive response. Deficiency or excess in innate immunity resulted in excessive proliferation of adaptive immune cells. Deficiency in any of the immune system components increased the probability of failure to clear the simulated viral infection. CONCLUSION: The behavior of the BIS matches both normal and pathological behavior patterns in a generic viral infection scenario. Thus, the BIS effectively translates mechanistic cellular and molecular knowledge regarding the innate and adaptive immune response and reproduces the immune system's complex behavioral patterns. The BIS can be used both as an educational tool to demonstrate the emergence of these patterns and as a research tool to systematically identify potential targets for more effective treatment strategies for diseases processes including hypersensitivity reactions (allergies, asthma), autoimmunity and cancer. We believe that the BIS can be a useful addition to the growing suite of in-silico platforms used as an adjunct to traditional research efforts.

Detection of intra-abdominal injury using diagnostic peritoneal lavage after shotgun wound to the abdomen.

BACKGROUND: The utility of diagnostic peritoneal lavage (DPL) as a diagnostic tool specifically for shotgun wound to the abdomen (SGWA) is unknown. This prospective study was undertaken to determine the sensitivity, specificity, and accuracy of DPL for the detection of intra-abdominal injuries following SGWA. METHODS: DPL was performed on all patients sustaining SGWA who lacked a clear indication for laparotomy. Patients exceeding 10,000 red blood cells (RBC)/mm were taken for exploratory laparotomy. A prospective database was kept with information on wound location, DPL result, findings upon laparotomy and outcome. RESULTS: Thirty-two DPLs were performed at our urban Level I trauma center for SGWA. Of these, 8 patients had a positive DPL. Upon laparotomy, 7 patients were found to have intra-abdominal injuries, 6 of which required surgical intervention. One patient had no peritoneal penetration or intra-abdominal injury. Of the 24 patients that had a negative DPL, 1 subsequently developed indications for laparotomy and was found to have operative injuries. For predicting intra-abdominal injuries DPL has a sensitivity, specificity and accuracy of 87.5%, 95.8% and 93.8%, respectively. CONCLUSION: For patients presenting with SGWA who do not present with indications for immediate laparotomy, DPL is a reliable indicator of intra-abdominal injury and need for operative intervention.

Trans-mediastinal gunshot wounds: are "stable" patients really stable?

Gunshot wounds that traverse the mediastinum frequently cause serious injury to the cardiac, vascular, pulmonary, and digestive structures contained within. Most patients present with unstable vital signs signifying the need for emergency operation. An occasional patient will present with stable vital signs. Work-ups for such a patient may range from surgical exploration to radiographic and endoscopic testing to mere observation. We report our experience with diagnostic work-up of the stable patient with a transmediastinal gunshot wound. All stable patients who present to our urban level I trauma center following a transmediastinal gunshot wound undergo diagnostic work-up consisting of chest radiograph, cardiac ultrasound, angiography, esophagoscopy, barium swallow, and bronchoscopy. The work-up is dependent on the trajectory of the missile. Information on these patients is kept in a prospective database maintained by the trauma attending physicians. This database was analyzed and comparisons were made using Student's t-test and the Fisher exact c2 as appropriate. Over a 68-month period, 50 stable patients were admitted following a transmediastinal gunshot wound. All of these patients had a chest radiograph followed by one or more of the above tests. 8 patients (16%) were found to have a mediastinal injury (4 cardiac, 3 vascular, and 1 tracheo-esophageal) requiring urgent operation (group 1). The remaining 42 patients (84%) did not have a mediastinal injury (group 2). There was no difference between groups with respect to blood pressure, pulse, respiratory rate, pH, base deficit, or initial chest tube output. There was one death in each group, and three complications in group 2. Patients may appear stable following a transmediastinal gunshot wound, even when they have life-threatening injuries. There is no difference in vital signs, blood gas, or hemothorax to indicate which patients have serious injuries. We advocate continued aggressive work-up of these patients to avoid missing an injury with disastrous consequences.