Inhibition of Integrin VLA-3 and Tetraspanin CD151 Protects Against Neutrophil-Mediated Endothelial Damage.

BACKGROUND: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil ß1 integrin Very Late Antigen-3 (VLA-3; α3ß1) and/or inhibition of the Tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. METHODS: Blood was obtained from septic patients or healthy donors. Neutrophils were purified and aliquots were treated with/without proinflammatory molecules. Confluent Human Umbilical Vascular Endothelial Cells (HUVECs) were activated with tumor necrosis factor (TNF-α). Electric Cell Impedance Sensing (ECIS) was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney test, Wilcoxon test, or repeated measures one-way analysis of variance (ANOVA). RESULTS: Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV and laminin suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. CONCLUSION: This report identifies VLA-3 and CD151, on the activated human neutrophil that are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.

Severity of critical illness correlates with CD3-low expression on iNKT-cells among septic surgical patients.

BACKGROUND: iNKT-cells are innate regulatory lymphocytes capable of directing immune and inflammatory responses to sepsis. Repeat stimulation of iNKT-cells leads to the induction of anergy with the emergence of a hyporesponsive CD3low iNKT-cell subpopulation. METHODS: iNKT-cells were isolated from critical ill surgical patients with sepsis and phenotyped for CD3 expression. This was correlated with degree of severity of illness, as denoted by APACHE-II score. RESULTS: Comparing healthy volunteers to critically ill septic patients, it was noted that increasing severity of sepsis was associated with increasing frequency of circulating CD3low-iNKT-cell populations. CONCLUSION: The emergence of CD3low -iNKT-cells may serve as a clinically translatable marker of degree of sepsis-induced immune dysfunction.

SPLENIC INVARIANT NATURAL KILLER T CELLS PLAY A SIGNIFICANT ROLE IN THE RESPONSE TO POLYMICROBIAL SEPSIS.

ABSTRACT: Background: Sepsis is marked by a dysregulated immune response to an infection. Invariant natural killer T cells ( i NKT cells) are a pluripotent lymphocyte subpopulation capable of affecting and coordinating the immune response to sepsis. The spleen is an important site of immune interactions in response to an infection. Splenic i NKT cells have emerged as important potential frontline mediators of chronic immune response. There are few data addressing the role splenic of i NKT cells in response to intra-abdominal polymicrobial sepsis. Methods: The cecal ligation and puncture model was used to create intra-abdominal sepsis in 8- to 12-week-old wild-type, i NKT -/- , or programmed cell death receptor-1 (PD-1) -/- mice. Twenty-four hours later, spleens were harvested. Flow cytometry was used for phenotyping using monoclonal antibodies. Cell sort was used to isolate i NKT cells. A macrophage cell line was used to assess i NKT cell-phagocyte interactions. Enzyme-linked immunosorbent assay was used for cytokine analysis. Results: Splenic i NKT-cell populations rapidly declined following induction of sepsis. Within i NKT-cell -/- mice, a distinct baseline hyperinflammatory environment was noted. Within wild type, sepsis induced an increase in splenic IL-6 and IL-10, whereas in i NKT -/- mice, there was no change in elevated IL-6 levels and a noted decrease in IL-10 expression. Further, following sepsis, PD-1 expression was increased upon spleen i NKT cells. With respect to PD-1 ligands upon phagocytes, PD-1 ligand expression was unaffected, whereas PD-L2 expression was significantly affected by the presence of PD-1. Conclusions: Invariant natural killer T cells play a distinct role in the spleen response to sepsis, an effect mediated by the checkpoint protein PD-1. Given that modulators are available in clinical trials, this offers a potential therapeutic target in the setting of sepsis-induced immune dysfunction.

Management of Acute Appendicitis in HIV/AIDs Patients: A 19-year Review from the National In-Patient Sample.

BACKGROUND: Acute Appendicitis (AA), one of the most common surgical emergencies, is usually managed operatively. There is a paucity of data addressing how HIV/AIDS affects management of acute uncomplicated appendicitis. METHODS: A retrospective review of HIV/AIDS positive (HPos) versus negative (HNeg) patients with acute, uncomplicated appendicitis over a 19-year period. The primary outcome was undergoing appendectomy. RESULTS: Among 912,779 AA patients, 4,291 patients were HPos. HIV rates increased from 3.8/1,000 in 2000 to 6.3 per 1,000 appendicitis cases in 2019 (p<0.001). HPos patients were older, less likely to have private insurance, and more likely to have psychiatric illnesses, hypertension, and a history of prior malignancy. HPos AA patients underwent operative intervention less often than HNeg AA patients (90.7% versus 97.7%;p<0.001). Overall, comparing HPos to HNeg patients, there was no difference in post-operative infections or mortality. CONCLUSION: HIV-positive status should not deter surgeons from offering definitive care for acute uncomplicated appendicitis.

Disparities in Decompressive Cranial Surgery Utilization in Severe Traumatic Brain Injury Patients without a Primary Extra-Axial Hematoma: A U.S. Nationwide Study.

OBJECTIVE: Decompressive craniectomy is recommended to reduce mortality in severe traumatic brain injury (TBI). Disparities exist in TBI treatment outcomes; however, data on disparities pertaining to decompressive craniectomy utilization is lacking. We investigated these disparities, focusing on race, insurance, sex, and age. METHODS: Hospitalizations (2004-2014) were retrospectively extracted from the Nationwide Inpatient Sample. The criteria included are as follows: age ≥18 years and indicators of severe TBI diagnosis. Poor outcomes were defined as discharge to institutional care and death. Multivariable logistic regression models were used to assess the effects of race, insurance, age, and sex, on craniectomy utilization and outcomes. RESULTS: Of 349,164 hospitalized patients, 6.8% (n = 23,743) underwent craniectomy. White (odds ratio [OR] = 0.50, 95% confidence interval [CI] = 0.44-0.57; P < 0.001) and Black (OR = 0.45, 95% CI = 0.32-0.64; P = 0.003) Medicare beneficiaries were less likely to undergo craniectomy. Medicare (P < 0.0001) and Medicaid beneficiaries (P < 0.0001) of all race categories had poorer outcomes than privately insured White patients. Black (OR = 1.2, 95% CI = 1.08-2.34; P = 0.001) patients with private insurance and Black (OR = 1.39, 95% CI = 1.22-1.58; P < 0.0001) Medicaid beneficiaries had poorer outcomes than privately insured White patients (P < 0.0001). Older patients (OR = 0.74, 95%, CI = 0.71-0.76; P < 0.001) were less likely to undergo craniectomy and were more likely to have poorer outcomes. Females (OR = 0.82, 95% CI = 0.76-0.88; P < 0.001) were less likely to undergo craniectomy. CONCLUSIONS: There are disparities in race, insurance status, sex, and age in craniectomy utilization and outcome. This data highlights the necessity to appropriately address these disparities, especially race and sex, and actively incorporate these factors in clinical trial design and enrollment.

Machine learning models to prognose 30-Day Mortality in Postoperative Disseminated Cancer Patients.

Patients with disseminated cancer at higher risk for postoperative mortality see improved outcomes with altered clinical management. Being able to risk stratify patients immediately after their index surgery to flag high risk patients for healthcare providers is vital. The combination of physician uncertainty and a demonstrated optimism bias often lead to an overestimation of patient life expectancy which can precent proper end of life counseling and lead to inadequate postoperative follow up. In this cohort study of 167,474 postoperative patients with multiple types of disseminated cancer, patients at high risk of 30-day postoperative mortality were accurately identified using our machine learning models based solely on clinical features and preoperative lab values. Extreme Gradient Boosting, Random Forest, and Logistic Regression machine learning models were developed on the cohort. Among 167,474 disseminated cancer patients, 50,669 (30.3%) died within 30 days of their index surgery; After preprocessing, 28 features were included in the model development. The cohort was randomly divided into 133,979 patients (80%) for training the models and 33,495 patients (20%) for testing. The extreme gradient boosting model had an AUC of 0.93 (95% CI: 0.926-0.931), the random forest model had an AUC of 0.93 (95% CI: 0.930-0.934), and the logistic regression model had an AUC of 0.90 (95% CI: 0.900-0.906 the index operation. Ultimately, Machine learning models were able to accurately predict short-term postoperative mortality among a heterogenous population of disseminated cancer patients using commonly accessible medical features. These models can be included in electronic health systems to guide clinical judgements that affect direct patient care, particularly in low-resource settings.

Machine learning methods to predict presence of residual cancer following hysterectomy.

Surgical management for gynecologic malignancies often involves hysterectomy, often constituting the most common gynecologic surgery worldwide. Despite maximal surgical and medical care, gynecologic malignancies have a high rate of recurrence following surgery. Current machine learning models use advanced pathology data that is often inaccessible within low-resource settings and are specific to singular cancer types. There is currently a need for machine learning models to predict non-clinically evident residual disease using only clinically available health data. Here we developed and tested multiple machine learning models to assess the risk of residual disease post-hysterectomy based on clinical and operative parameters. Data from 3656 hysterectomy patients from the NSQIP dataset over 14 years were used to develop models with a training set of 2925 patients and a validation set of 731 patients. Our models revealed the top postoperative predictors of residual disease were the initial presence of gross abdominal disease on the diaphragm, disease located on the bowel mesentery, located on the bowel serosa, and disease located within the adjacent pelvis prior to resection. There were no statistically significant differences in performances of the top three models. Extreme gradient Boosting, Random Forest, and Logistic Regression models had comparable AUC ROC (0.90) and accuracy metrics (87-88%). Using these models, physicians can identify gynecologic cancer patients post-hysterectomy that may benefit from additional treatment. For patients at high risk for disease recurrence despite adequate surgical intervention, machine learning models may lay the basis for potential prospective trials with prophylactic/adjuvant therapy for non-clinically evident residual disease, particularly in under-resourced settings.

A Case of Recurrent Malignant Melanoma of the Left Foot with In-Transit Metastases.

We report a 73-year-old male with recurrent amelanotic malignant melanoma of the left foot with in-transit metastases to the left thigh. In-transit metastatic melanoma can often represent a diagnostic and therapeutic challenge for physicians. This patient was treated with talimogene laherparepvec injections (T-VEC; Imlygic) in the left inguinal and the left plantar region every two weeks for one year as oncolytic viral therapy for advanced non- operable malignant melanoma. He then received consistent follow-up including blood work and PET scans every four months, and he also required further lymph node surgical dissection. To date, our patient has survived 3 years and 11 months, which is 27 months longer than the esti- mated median survival of 1 year 8 months for patients diagnosed with in-transit metastatic melanoma.

Survival and Pulmonary Injury After Neonatal Sepsis: PD1/PDL1's Contributions to Mouse and Human Immunopathology.

Morbidity and mortality associated with neonatal sepsis remains a healthcare crisis. PD1-/- neonatal mice endured experimental sepsis, in the form of cecal slurry (CS), and showed improved rates of survival compared to wildtype (WT) counterparts. End-organ injury, particularly of the lung, contributes to the devastation set forth by neonatal sepsis. PDL1-/- neonatal mice, in contrast to PD1-/- neonatal mice did not have a significant improvement in survival after CS. Because of this, we focused subsequent studies on the impact of PD1 gene deficiency on lung injury. Here, we observed that at 24 h post-CS (but not at 4 or 12 h) there was a marked increase in pulmonary edema (PE), neutrophil influx, myeloperoxidase (MPO) levels, and cytokine expression sham (Sh) WT mice. Regarding pulmonary endothelial cell (EC) adhesion molecule expression, we observed that Zona occludens-1 (ZO-1) within the cell shifted from a membranous location to a peri-nuclear location after CS in WT murine cultured ECs at 24hrs, but remained membranous among PD1-/- lungs. To expand the scope of this inquiry, we investigated human neonatal lung tissue. We observed that the lungs of human newborns exposed to intrauterine infection had significantly higher numbers of PD1+ cells compared to specimens who died from non-infectious causes. Together, these data suggest that PD1/PDL1, a pathway typically thought to govern adaptive immune processes in adult animals, can modulate the largely innate neonatal pulmonary immune response to experimental septic insult. The potential future significance of this area of study includes that PD1/PDL1 checkpoint proteins may be viable therapeutic targets in the septic neonate.

Surgical Infection Society Guidance for Restoration of Surgical Services during the Coronavirus Disease-2019 Pandemic.

Background: As the coronavirus disease-2019 (COVID-19) pandemic continues globally, high numbers of new infections are developing nationwide, particularly in the U.S. Midwest and along both the Atlantic and Pacific coasts. The need to accommodate growing numbers of hospitalized patients has led facilities in affected areas to suspend anew or curtail normal hospital activities, including elective surgery, even as earlier-affected areas normalized surgical services. Backlogged surgical cases now number in the tens of millions globally. Facilities will be hard-pressed to address these backlogs, even absent the recrudescence of COVID-19. This document provides guidance for the safe and effective resumption of surgical services as circumstances permit. Methods: Review and synthesis of pertinent international peer-reviewed literature, with integration of expert opinion. Results: The "second-wave" of serious infections is placing the healthcare system under renewed stress. Surgical teams likely will encounter persons harboring the virus, whether symptomatic or not. Continued vigilance and protection of patients and staff remain paramount. Reviewed are the impact of COVID-19 on the surgical workforce, considerations for operating on a COVID-19 patient and the outcomes of such operations, the size and nature of the surgical backlog, and the logistics of resumption, including organizational considerations, patient and staff safety, preparation of the surgical candidate, and the role of enhanced recovery programs to reduce morbidity, length of stay, and cost by rational, equitable resource utilization. Conclusions: Resumption of surgical services requires institutional commitment (including teams of surgeons, anesthesiologists, nurses, pharmacists, therapists, dieticians, and administrators). Structured protocols and equitable implementation programs, and iterative audit, planning, and integration will improve outcomes, enhance safety, preserve resources, and reduce cost, all of which will contribute to safe and successful reduction of the surgical backlog.

Surgical Infection Society Guidance for Operative and Peri-Operative Care of Adult Patients Infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.

Impact of Multi-Drug-Resistant Pneumonia on Outcomes of Critically Ill Trauma Patients.

Background: Rates of infections with multi-drug-resistant organisms (MDROs) are increasing among critically ill patients. Among non-surgical patients, MDROs increase directly the risk of adverse secondary events including death. However, similar effects do not appear to occur among surgical patients. Specifically, among critically injured trauma patients, it is unknown whether degree of injury versus the presence of an MDRO increases the risk of death. Methods: This is a retrospective chart review of admitted adult trauma patients. Data included demographics, medical comorbidities, injury severity score, infections, occurrence of pneumonia including microbiology sensitivity profile, hospital course, and outcomes. Results: Patients requiring adminission to the intensive care unit (ICU) were more severely injured with greater degree of thoracic and head trauma and had a greater burden of pre-trauma medical comorbidities. Among those admitted to the ICU, 93 patients developed pneumonia. Patients who developed pneumonia were younger and more severely injured, with higher rates of thoracic and head injuries and higher rates of smoking. Development of pneumonia was associated with worse outcomes. However, among patients with pneumonia, comparing MDRO to pan-sensitive (PanSens) infections, PanSens infection occurred earlier and were more likely associated with pre-trauma smoking status. There was no difference in injury patterns, medical comorbidities, or outcomes. Conclusion: The development of pneumonia among trauma patients reflects degree of injury and underlying medical status. However, development of MDRO versus PanSens pneumonia did not affect trauma-related outcomes further. This information will guide family discussions and critical care decisions better among vulnerable trauma patients.

Herpes Virus Entry Mediator (HVEM): A Novel Potential Mediator of Trauma-Induced Immunosuppression.

BACKGROUND: Herpes virus entry mediator (HVEM) is a coinhibitory molecule which can both stimulate and inhibit host immune responses. Altered expression of HVEM and its ligands is associated with increased nosocomial infections in septic patients. We hypothesize critically ill trauma patients will display increased lymphocyte HVEM expression and that such alteration is predictive of infectious events. MATERIALS AND METHODS: Trauma patients prospectively enrolled from the ICU were compared with healthy controls. Leukocytes were isolated from whole blood, stained for CD3 (lymphocytes) and HVEM, and evaluated by flow cytometry. Charts were reviewed for injuries sustained, APACHE II score, hospital course, and secondary infections. RESULTS: Trauma patients (n = 31) were older (46.7 ± 2.4 versus 36.8 ± 2.1 y; P = 0.03) than healthy controls (n = 10), but matched for male sex (74% versus 60%; P = 0.4). Trauma patients had higher presenting WBC (13.9 ± 1.3 versus 5.6 ± 0.5 × 106/mL; P = 0.002), lower percentage of CD3+ lymphocytes (7.5% ± 0.8 versus 22.5% ± 0.9; P < 0.001), but significantly greater expression of HVEM+/CD3+ lymphocytes (89.6% ± 1.46 versus 67.3% ± 1.7; P < 0.001). Among trauma patients, secondary infection during the hospitalization was associated with higher APACHE II scores (20.6 ± 1.6 versus 13.6 ± 1.4; P = 0.03) and markedly lower CD3+ lymphocyte HVEM expression (75% ± 2.6 versus 93% ± 0.7; P < 0.01). CONCLUSIONS: HVEM expression on CD3+ cells increases after trauma. Patients developing secondary infections have less circulating HVEM+CD3+. This implies HVEM signaling in lymphocytes plays a role in maintaining host defense to infection in after trauma. HVEM expression may represent a marker of infectious risk as well as a potential therapeutic target, modulating immune responses to trauma.

Wandering spleen in a geriatric patient - a rare presentation of gastric volvulus.

We report atypical gastric outlet obstruction in a geriatric patient caused by acute mesenteroaxial gastric volvulus precipitated by a wandering spleen.

Dismal outcomes following damage control laparotomy in injured older adults, a cohort study.

BACKGROUND: The population of older adults is rapidly growing and more older patients are presenting with abdominal trauma. Outcomes have not been well defined for patients that require a damage control approach(DCL). METHODS: This was a retrospective study at a level one trauma center of patients age 65 years and older with abdominal trauma that required DCL. Outcomes reviewed included mortality, length of stay, discharge disposition. Presenting vital signs and laboratories were reviewed to identify predictors of mortality. RESULTS: 31 older patients(mean age 75.2 years) underwent DCL. Twenty-four of 31(77.4%) older patients died. Seven of 7 older DCL survivors were discharged to a rehabilitation center or nursing home. In comparisons of older DCL nonsurvivors and survivors there were not differences in presenting HR(90 versus 96; p = 0.56) or SBP in the emergency room(107 versus 116; p = 0.51). No differences in initial lactate or change in lactate concentration were found between nonsurvivors and survivors. Fifteen of 24 nonsurvivors died from multisystem organ failure. CONCLUSIONS/IMPLICATIONS: The mortality rate of older patients that require damage control approach for is extremely high. Presenting vital signs and laboratory markers may not be useful in older patients to predict mortality.

Group 2 Innate Lymphoid Cells (ILC2s) Are Key Mediators of the Inflammatory Response in Polymicrobial Sepsis.

Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells and inversely decline in the liver at 24 hours after septic insult. Sepsis also resulted in changes in ILC2 effector cytokine (IL-13) and activating cytokine (IL-33) in the plasma of mice and human patients in septic shock. Of interest, the sepsis-induced changes in cytokines were abrogated in mice deficient in functionally invariant natural killer T cells. Mice deficient in IL-13-producing cells, including ILC2s, had a survival advantage after sepsis along with decreased morphologic evidence of tissue injury and reduced IL-10 levels in the peritoneal fluid. Administration of a suppressor of tumorigenicity 2 (IL-33R) receptor-blocking antibody led to a transient survival advantage. Taken together, these findings suggest that ILC2s may play an unappreciated role in mediating the inflammatory response in both mice and humans; further, modulating ILC2 response in vivo may allow development of immunomodulatory strategies directed against sepsis.

Outcomes in nursing home patients with traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability in the United States. In survivors, traumatic brain injury remains a leading contributor to long-term disability and results in many patients being admitted to skilled nursing facilities for postacute care. Despite this very large population of traumatic brain injury patients, very little is known about the long-term outcomes of traumatic brain injury survivors, including rates of discharge to home or risk of death in long-term nursing facilities. We hypothesized that patient demographics and functional status influence outcomes of patients with traumatic brain injury admitted to skilled nursing facilities. METHODS: We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries aged 65 and older discharged alive and directly from hospital to a skilled nursing facility between 2011 and 2014 using the prospectively maintained Federal Minimum Data Set combined with Medicare claims data and the Centers for Medicare and Medicaid Services Vital Status files. Records were reviewed for demographic and clinical characteristics at admission to the skilled nursing facility, including age, sex, cognitive function, ability to communicate, and motor function. Activities of daily living were reassessed at discharge to calculate functional improvement. We used robust Poisson regression with skilled nursing facility fixed effects to calculate relative risks and 99% confidence intervals for mortality and functional improvement associated with the demographic and clinical characteristics present at admission. Linear regression was used to calculate adjusted mean duration of stay. RESULTS: Overall, 87,292 Medicare fee-for-service beneficiaries with traumatic brain injury were admitted to skilled nursing facilities. The mean age was 84 years, with 74% of patients older than age 80. Generally, older age, male sex, and poor cognitive or functional status at admission to a skilled nursing facility were associated with increased risk for poorer outcomes. Older patients (age ≥80 years) with traumatic brain injury had a 1.5 times greater risk of death within 30 days of admission compared with adults younger than 80 years (relative risk = 1.49, 99% confidence interval = 1.36, 1.64). Women were 37% less likely to die than men were (relative risk = 0.63, 99% confidence interval = 0.59, 0.68). The risk of death was greater for patients with poor cognitive function (relative risk = 2.55, 99% confidence interval = 2.32, 2.77), substantial motor impairment (relative risk = 2.44, 99% confidence interval = 2.16, 2.77), and patients with impairment in communication (relative risk = 2.58, 99% confidence interval = 2.32, 2.86) compared with those without the respective deficits. One year after admission, these risk factors continued to confer excess risk for mortality. Duration of stay was somewhat greater for older patients (30.1 compared with 27.5 average days) and patients with cognitive impairment (31.7 vs 27.5 average days). At discharge, patients with cognitive impairment (relative risk = 0.86, 99% confidence interval = 0.83, 0.88) and impairment in the ability to communicate (relative risk = 0.67, 99% confidence interval = 0.54, 0.82) were less likely to improve in physical function. CONCLUSION: Our results suggest that among patients with traumatic brain injury admitted to skilled nursing facilities, the likelihood of adverse outcomes varies significantly by key demographic and clinical characteristics. These findings may facilitate setting expectations among patients and families as well as providers when these patients are admitted to skilled nursing facilities for rehabilitation after their acute episode.

Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from critically ill patients.

BACKGROUND: Multi-organ failure occurs during critical illness and is mediated in part by destructive neutrophil-to-endothelial interactions. The ß2 integrin receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the adhesion of activated neutrophils to inflamed endothelia which, when prolonged and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small molecule allosteric activator of CR3 and has been shown to promote adhesion of blood neutrophils to inflamed endothelium and restrict tissue infiltration. Therefore, LA-1 offers a novel mechanism of anti-inflammatory action by activation, rather than inhibition, of the neutrophil CR3 integrin. However, whether promotion of neutrophil-to-endothelial interaction by this novel therapeutic is of benefit or detriment to endothelial barrier function is not known. METHODS: Critically ill septic and trauma patients were prospectively enrolled from the surgical and the trauma ICU. Blood was collected from these patients and healthy volunteers. Neutrophils were isolated by dextran sedimentation and adhered to TNF-α (tumor necrosis factor-α)-activated human umbilical vein endothelial (HUVEC) monolayers in the presence or absence of fMLP (formylmethionine-leucine-phenylalanine) and/or LA-1. Electric cell-substrate impedance sensing (ECIS) and exposure of underlying collagen were used to quantify endothelial barrier function and permeability. RESULTS: Neutrophils from critically ill trauma and septic patients caused similar degrees of endothelial barrier disruption which exceeded that caused by cells obtained from healthy controls both kinetically and quantitatively. LA-1 protected barrier function in the absence and presence of fMLP which served as a secondary stimulant to cause maximal loss of barrier function. LA-1 protection was also observed by quantifying collagen exposure underlying endothelial cells challenged with fMLP-stimulated neutrophils. LA-1 treatment resulted in decreased migration dynamics of neutrophils crawling on an endothelial monolayer with reduced speed (µm/s = 0.25 ± 0.01 vs. 0.06 ± 0.01, p < 0.05), path length (µm = 199.5 ± 14.3 vs. 42.1 ± 13.0, p < 0.05), and displacement (µm = 65.2 ± 4.7 vs. 10.4 ± 1.3; p < 0.05). CONCLUSION: Neutrophils from patients with trauma or sepsis cause endothelial barrier disruption to a similar extent relative to each other. The CR3 agonist LA-1 protects endothelial barrier function from damage caused by neutrophils obtained from both populations of critically ill patients even when exposed to secondary stimulation.

A Randomized Controlled Trial of Video Education versus Skill Demonstration: Which Is More Effective in Teaching Sterile Surgical Technique?

BACKGROUND: Video education has many advantages over traditional education including efficiency, convenience, and individualized learning. Learning sterile surgical technique (SST) is imperative for medical students, because proper technique helps prevent surgical site infections (SSIs). We hypothesize that video education is at least as effective as traditional skill demonstration in teaching first-year medical students SST. METHODS: A video series was created to demonstrate SST ( https://www.youtube.com/playlist?list=PLcRU-gvOmxE2mwMWkowouBkxGXkLZ8Uis ). A randomized controlled trial was designed to assess which education method best teaches SST: video education or skill demonstration. First-year medical students (n = 129) were consented and randomly assigned into two groups: those who attended a skill demonstration (control group; n = 70) and those who watched the video series (experimental group; n = 59). The control group attended a pre-existing 90-minute nurse educator-led skill demonstration. Participants then completed a 30-item multiple choice quiz to test their knowledge. Each group then received the alternate education method and completed a 23-item follow-up survey to determine their preferred method. RESULTS: Seven 2- to 6-minute videos (30 minutes total) were created on surgical attire, scrubbing, gowning and gloving, and maintaining sterility. The experimental group (n = 51) scored higher on the quiz compared with the control group (n = 63) (88% ± 1% versus 72% ± 1%; p < 0.0001). Students preferred the videos when it came to convenience, accessibility, efficiency, and review, and preferred the skill demonstration when it came to knowledge retention, preparedness, and ease of completion. CONCLUSIONS: Video education is superior to traditional skill demonstration in providing medical students with knowledge of SST. Students identified strengths to each method of teaching. Video education can augment medical students' knowledge prior to their operating room experience to ensure that a sterile environment is maintained for patients. The ultimate goal is to reduce SSIs.

Trauma morning report is the ideal environment to teach and evaluate resident communication and sign-outs in the 80 hour work week.

BACKGROUND: The 80h work week has raised concerns that complications may increase due to multiple sign-outs or poor communication. Trauma Surgery manages complex trauma and acute care surgical patients with rapidly changing physiology, clinical demands and a large volume of data that must be communicated to render safe, effective patient care. Trauma Morning Report format may offer the ideal situation to study and teach sign-outs and resident communication. MATERIALS AND METHODS: Surgery Residents were assessed on a 1-5 scale for their ability to communicate to their fellow residents. This consisted of 10 critical points of the presentation, treatment and workup from the previous night's trauma admissions. Scores were grouped into three areas. Each area was scored out of 15. Area 1 consisted of Initial patient presentation. Area 2 consisted of events in the trauma bay. Area 3 assessed clarity of language and ability to communicate to their fellow residents. The residents were assessed for inclusion of pertinent positive and negative findings, as well as overall clarity of communication. In phase 1, residents were unaware of the evaluation process. Phase 2 followed a series of resident education session about effective communication, sign-out techniques and delineation of evaluation criteria. Phase 3 was a resident-blinded phase which evaluated the sustainability of the improvements in resident communication. RESULTS: 50 patient presentations in phase 1, 200 in phase 2, and 50 presentations in phase 3 were evaluated. Comparisons were made between the Phase 1 and Phase 2 evaluations. Area 1 (initial events) improved from 6.18 to 12.4 out of 15 (p<0.0001). Area 2 (events in the trauma bay) improved from 9.78 to 16.53 (p<0.0077). Area 3 (communication and language) improved from 8.36 to 12.22 out of 15 (P<0.001). Phase 2 to Phase 3 evaluations were similar, showing no deterioration of skills. CONCLUSIONS: Trauma Surgery manages complex surgical patients, with rapidly changing physiologic and clinical demands. Trauma Morning Report, with diverse attendance including surgical attendings and residents in various training years, is the ideal venue for real-time teaching and evaluation of sign-outs and reinforcing good communication skills in residents.