Background Millions of patients who survive medical and surgical general ICU care every year suffer from newly acquired long-term cognitive impairment and profound physical and functional disabilities. To overcome the current reality in which patients receive inadequate rehabilitation, we devised a multi-faceted, in-home tele-rehabilitation program implemented using social workers and psychology technicians with the goal of improving cognitive and functional outcomes. Methods This was a single-site, feasibility, pilot randomized trial of 21 general medical/surgical ICU survivors (8 controls and 13 intervention patients) with either cognitive or functional impairment at hospital discharge. After discharge, study controls received usual care (sporadic rehabilitation) while intervention patients received a combination of in-home cognitive, physical, and functional rehabilitation over a 3-month period via a social worker or master's level psychology technician utilizing telemedicine to allow specialized multi-disciplinary treatment. Interventions over 12 weeks included 6 in-person visits for cognitive rehabilitation and 6 televisits for physical/functional rehabilitation. Outcomes were measured at the completion of the rehabilitation program (i.e., at 3 months) with cognitive functioning as the primary outcome. Analyses were conducted using linear regression to examine differences in 3-month outcomes between treatment groups while adjusting for baseline scores. Results Patients tolerated the program with only 1 adverse event (AE) reported. At baseline both groups were well-matched. At 3-month follow-up, intervention group patients demonstrated significantly improved cognitive executive functioning on the widely used and well-normed Tower Test (TOWER) (for planning and strategic thinking) versus controls [13.0 (Interquartile Range, IQR 11.5 to14.0) vs. 7.5 (4.0 to 8.5), adjusted p<0.01]. Intervention group patients also reported better performance (i.e., lower score) on one of the most frequently employed measures of functional status [Functional Activities Questionnaire (FAQ)] at 3 months vs. controls [1.0 (0.0 to 3.0) vs. 8.0 (6.0 to 11.8), adjusted p=0.04]. Conclusions A multi-component rehabilitation program for ICU survivors combining cognitive, physical, and functional training appears feasible and possibly effective in improving cognitive performance and functional outcomes in just 3 months. Future investigations with a larger sample size should be conducted to build on this pilot, feasibility program and to confirm these results as well as to elucidate the elements of rehabilitation contributing most to improved outcomes.

Background Systemic blockade of Tissue Factor (TF) attenuates acute lung injury (ALI) in animal models of sepsis but the effects of global TF deficiency are unknown. Hypothesis We used mice with complete knockout of mouse TF and low levels (~1%) of human TF (LTF mice) to test the hypothesis that global TF deficiency attenuates lung inflammation in direct lung injury. Methods LTF mice were treated with 10 μg of lipopolysaccharide (LPS) or vehicle administered by direct intratracheal (IT) injection and studied at 24 hours. Results Contrary to our hypothesis, LTF mice had increased lung inflammation and injury as measured by bronchoalveolar lavage cell count (3.4 × 105 WT LPS versus 3.3 × 105 LTF LPS, p=0.947) and protein (493 μg/ml WT LPS versus 1014 μg/ml LTF LPS, p=0.006), proinflammatory cytokines (TNF-α, IL-10, IL-12, p<0.035 WT LPS versus LTF LPS) and histology compared to wild type mice. LTF mice also had increased hemorrhage and free hemoglobin in the airspace accompanied by increased oxidant stress as measured by lipid peroxidation products (F2-Isoprostanes and Isofurans). Conclusions These findings indicate that global TF deficiency does not confer protection in a direct lung injury model. Rather, TF deficiency causes increased intra-alveolar hemorrhage following LPS leading to increased lipid peroxidation. Strategies to globally inhibit tissue factor may be deleterious in patients with ALI.

Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI.Keywords: coagulation; fibrin; pulmonary; acute respiratory distress syndrome; alveolar capillary barrier permeability Clinical RelevanceThis study evaluates the role of tissue factor (TF) in direct acute lung injury using cell-specific genetic approaches. We identify the lung epithelium as the major source of TF in the airspace. Loss of epithelial TF increases lung injury, impairs coagulation, results in lung hemorrhage, and disrupts alveolar-capillary barrier permeability. These findings identify a potential new target for treatment of severe lung injury in humans.A pathologic hallmark of severe acute lung injury (ALI) in humans is intra-alveolar fibrin deposition, forming hyaline membranes lining the airspace (1). Activation of the tissue factor (TF) pathway is a major driver of coagulation in the airspace (2-5). We previously demonstrated a critical role for TF in protection from ALI caused by intratracheal LPS administration (2). LTF mice, which lack murine TF and express 1% of endogenous levels of human TF to overcome embryonic lethality, developed more severe ALI in response to intratracheal LPS than littermate controls. LTF mice had a local coagulation defect in the airspace, increased histologic lung injury, increased alveolar-capillary

Rationale: Effective teamwork is fundamental to the management of medical emergencies, and yet the best method to teach teamwork skills to trainees remains unknown.Objectives: In a cohort of incoming internal medicine interns, we tested the hypothesis that expert demonstration of teamwork principles and participation in high-fidelity simulation would each result in objectively assessed teamwork behavior superior to traditional didactics.Methods: This was a randomized, controlled, parallel-group trial comparing three teamwork teaching modalities for incoming internal medicine interns. Participants in a single-day orientation at the Vanderbilt University Center for Experiential Learning and Assessment were randomized 1:1:1 to didactic, demonstration-based, or simulation-based instruction and then evaluated in their management of a simulated crisis by five independent, blinded observers using the Teamwork Behavioral Rater score. Clinical performance was assessed using the American Heart Association Advanced Cardiac Life Support algorithm and a novel "Recognize, Respond, Reassess" score.Measurements and Main Results: Participants randomized to didactics (n = 18), demonstration (n = 17), and simulation (n = 17) were similar at baseline. The primary outcome of average overall Teamwork Behavioral Rater score for those who received demonstration-based training was similar to simulation participation (4.40 6 1.15 vs. 4.10 6 0.95, P = 0.917) and significantly higher than didactic instruction (4.40 6 1.15 vs. 3.10 6 0.51, P = 0.045). Clinical performance scores were similar between the three groups and correlated only weakly with teamwork behavior (coefficient of determination [R s 2 ] = 0.267, P , 0.001).Conclusions: Among incoming internal medicine interns, teamwork training by expert demonstration resulted in similar teamwork behavior to participation in high-fidelity simulation and was more effective than traditional didactics. Clinical performance was largely independent of teamwork behavior and did not differ between training modalities.

BackgroundIt is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes.MethodsA total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times.ResultsARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50–0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49–0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time.ConclusionsElevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1700-7) contains supplementary material, which is available to authorized users.