Healthy Aging Brain Care Monitor, Caregiver Version: Screening for Post-Intensive Care Syndrome.

BACKGROUND: Cognitive impairment is common in intensive care unit survivors, pointing to the potential utility of a caregiver-based tool to screen for post-intensive care syndrome. OBJECTIVE: To validate the Healthy Aging Brain Care Monitor, Caregiver Version (HABC-M CG), as a caregiver-based tool to screen for post-intensive care syndrome. METHODS: A total of 116 patients who survived a stay in the intensive care unit completed standardized assessments of cognition, psychological symptoms, and physical functioning, and their caregivers completed the HABC-M CG. The Cronbach α was used to measure the internal consistency of the scale items. Validity of the HABC-M CG versus comparison tests was measured using the Spearman rank correlation. Generalized linear models were used to adjust for age, sex, and education level. RESULTS: The total scale and all subscales of the HABC-M CG showed excellent internal consistency (Cronbach α = 0.88-0.93). Scores on the psychological subscale correlated with standardized measures of depressive symptoms (Spearman ρ = 0.58). Scores on the cognitive subscale correlated with the Mini-Mental State Examination score (Spearman ρ = -0.33). Scores on the functional subscale correlated with scores on the Physical Self-Maintenance Scale (Spearman ρ = -0.36). CONCLUSION: The HABC-M CG is a valid informant-based clinical tool for the assessment of symptoms of post- intensive care syndrome.

Serum Biomarkers in Postoperative Delirium After Esophagectomy.

BACKGROUND: Esophagectomy is associated with postoperative delirium, but its pathophysiology is not well defined. We conducted this study to measure the relationship among serum biomarkers of inflammation and neuronal injury and delirium incidence and severity in a cohort of esophagectomy patients. METHODS: Blood samples were obtained from patients preoperatively and on postoperative days 1 and 3 and were analyzed for S100 calcium-binding protein B, C-reactive protein (CRP), interleukin (IL) 8 and IL-10, tumor necrosis factor-α, and insulin-like growth factor 1. Delirium was assessed twice daily using the Richmond Agitation Sedation Scale and Confusion Assessment Method for Intensive Care Unit. Delirium severity was assessed once daily with the Delirium Rating Scale-Revised-98. RESULTS: Samples from 71 patients were included. Preoperative biomarker concentrations were not associated with postoperative delirium. Significant differences in change in concentrations from preoperatively to postoperative day 1 were seen in IL-8 (delirium, 38.6; interquartile range [IQR], 29.3-69.8; no delirium, 24.8; IQR, 16.0-41.7, P = .022), and IL-10 (delirium, 26.1; IQR, 13.9-36.7; no delirium, 12.4; IQR, 7.7-25.7; P = .025). Greater postoperative increase in S100 calcium-binding protein B (Spearman r = 0.289, P = .020) and lower levels of insulin-like growth factor 1 were correlated with greater delirium severity (Spearman r = -0.27, P = .040). Greater CRP change quartiles were associated with higher delirium incidence adjusting for severity of illness (odds ratio, 1.68; 95% confidence interval, 1.03-2.75; P = .037) or comorbidities (odds ratio, 1.70; 95% confidence interval, 1.05-2.76, P = .030). CONCLUSIONS: Differences in change in serum CRP, IL-8, and IL-10 concentrations were associated with postoperative delirium, suggesting biomarker measurement early in the postoperative course is associated with delirium.

Feasibility of a virtual reality intervention in the intensive care unit.

BACKGROUND: Delirium prevention requires optimal management of pain and anxiety. Given the limitations of current pharmacologic interventions, evaluation of novel non-pharmacological interventions is required. Virtual reality (VR) stimulation may be a promising intervention because of its capability to reduce psychophysiological stress, pain, and anxiety and to restore cognitive and attentional capacities. OBJECTIVE: To ascertain patients' and providers' perceptions of acceptability and safety of VR intervention in the intensive care unit (ICU). METHODS: We enrolled a cohort of 15 ICU patients and 21 health care providers to administer a 15-minute session showing a relaxing beach scene with VR headsets and nature sound effects. Participants were then asked to rate their experiences on a Likert scale survey. RESULTS: The majority of patients (86%, 12 of 14) rated the headsets as moderately to very comfortable. All had moderate or greater sense of presence in the virtual environment, and 79% (11 of 14) rated their overall experience at 3 or greater (5 indicating that they enjoyed it very much). Seventy-one percent (10 of 14) of the patients felt that their anxiety was better with VR, and 57% (8 of 14) did not notice a change in their pain or discomfort. All health care providers found the headset to be at least moderately comfortable and felt a moderate or greater sense of presence. All providers concluded that VR therapy should be available for their patients. Both groups experienced minimal side effects. CONCLUSION: In this prospective study of perceptions of VR therapy for ICU patients and health care providers, there was a high level of acceptance, with minimal side effects, for both groups despite their low levels of prior experience with virtual reality and video gaming.

Distinct Factors Secreted by Adipose Stromal Cells Protect the Endothelium From Barrier Dysfunction and Apoptosis.

We have shown previously that adipose stromal cell (ASC)-derived conditioned media (CM) limited lung injury, endothelial barrier dysfunction, and apoptosis. Here, we used endothelial hyperpermeability and apoptosis assays to investigate how concentration processes affect endothelium-directed bioactivity of ASC-CM and to gain information on the nature of bioactive factors. Comparison of ASC-CM concentrated with differential molecular weight (MW) cutoff filters showed that endothelial barrier protection depended on the species-specific factors in ASC-CM fractionated with MW > 50 kDa. Known barrier regulators-keratin growth factor (KGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF)-were detected in ASC-CM fraction of > 100 kDa. Pretreatment of endothelial monolayers with concentrations of KGF, VEGF, and HGF detected in ASC-CM showed that only KGF and HGF protect the endothelium from barrier dysfunction. Depletion of KGF and HGF from ASC-CM attenuated ASC-CM's ability to protect the endothelial barrier. In contrast to barrier-protective factors, apoptosis-protective factors fractionated with MW < 3 kDa and were not species-specific. Application of donors of apoptosis-mitigating gases showed that the CO donor carbon monoxide-releasing molecule 2 (CORM2) protected the endothelium from apoptosis, while the H2S donor NaSH did not. Knockdown of CO-generating heme oxygenase 1 in ASC attenuated ASC-CM's ability to protect the endothelium from apoptosis. We have shown that tumor necrosis factor alpha (TNFα)-induced apoptosis in endothelium is c-Jun N-terminal kinase (JNK)-dependent, and JNK activation is inhibited by ASC-CM pretreatment of endothelial cells. ASC-CM from heme oxygenase 1-depleted ASC displayed attenuated ability to suppress endothelial JNK activation, suggesting that CO-mediated protection of the endothelium from apoptosis is achieved by the downregulation of the JNK pathway. Altogether, our results demonstrate that the concentration of ASC-CM with low MW cutoff filters significantly reduces its anti-apoptotic activity while preserving its barrier-protective activity.

Whole-Body Vibration Training Increases Stem/Progenitor Cell Circulation Levels and May Attenuate Inflammation.

INTRODUCTION: Whole-body vibration training (WBVT) may benefit individuals with difficulty participating in physical exercise. The objective was to explore the effects of WBVT on circulating stem/progenitor cell (CPC) and cytokine levels. METHODS: Healthy male subjects each performed three activities randomly on separate days: (1) standing platform vibration, (2) repetitive leg squat exercise; and (3) in combination. Pre- and post-activity blood samples were drawn. Cell populations were characterized using flow cytometry. Biomarkers were analyzed using enzyme-linked immunosorbent assays. RESULTS: CPC levels increased significantly 21% with exercise alone (1465 ± 202-1770 ± 221 cells/mL; P = 0.017) and 33% with vibration alone in younger participants (1918 ± 341-2559 ± 496; P = 0.02). Angiogenic CPCs increased 39% during combined activity in younger (633 ± 128-882 ± 181; P = 0.05). Non-angiogenic CPCs increased 42% with vibration alone in younger (1181 ± 222-1677 ± 342; P = 0.04), but 32% with exercise alone in older participants (801 ± 251-1053 ± 325; P = 0.05). With vibration alone, anti-inflammatory cytokine interleukin-10 increased significantly (P < 0.03), although inflammatory interleukin-6 decreased (P = 0.056); tumor necrosis factor-alpha (P < 0.01) and vascular endothelial growth factor levels increased (P < 0.005), which are synergistically pro-angiogenic. CONCLUSIONS: WBVT may have positive vascular and anti-inflammatory effects. WBVT could augment or serve as an exercise surrogate in warfighters and others who cannot fully participate in exercise programs, having important implications in military health.

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors.

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28- T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28- (-28%), CD8+CD28- T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1-LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression.