Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model.

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min-1 30 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.5nm and 83m) transport returning to the laboratory. The ReFit algorithm kept all animals stable for ~ 3 h. Thus, ReFit algorithm can diagnose and treat ongoing hemorrhagic shock independent to the site of care or during transport. These results have implications for treatment of critically ill patients in remote, austere and contested environments and during transport to a higher level of care.

[Epilepsy surgery seems underutilized in Sweden]. / Epilepsikirurgin är underutny­­ttjad ­ fler bör hänvisas till utredning.

Epilepsy surgery should be considered for individuals with drug-resistant focal epilepsy. The pre-surgical evaluation is highly multi-disciplinary and performed by a team consisting of neurologists, neurophysiologists, neurosurgeons, neuroradiologists, neuropsychologists, biomedical scientists, speech-language pathologists and nursing staff. The evaluation comprises of a meticulous medical history with focus on seizure semiology, a 3 Tesla MRI, ictal video-EEG, neuropsychological evaluation and sometimes also MEG, nTMS, fMRI, PET or SISCOM/ictal SPECT. Occasionally, invasive monitoring with intracranial electrodes is necessary. Surgical options in treatment of epilepsy range from open resections of epileptogenic areas to focal ablations and neurostimulation. There is evidence of epilepsy surgery being an effective treatment in carefully selected cases. Epilepsy surgery seems underutilized in Sweden and referrals for epilepsy surgery work-up need to increase.

The Microcirculatory Response to Endotoxemia and Resuscitation Is a Marker of Regional Renal Perfusion, Renal Metabolic Stress, and Tubular Injury.

Aims: We sought to investigate the relationship between macrohemodynamic resuscitation and microcirculatory parameters with the response of microcirculatory flow, tissue-specific parameters of metabolic stress and injury. We hypothesized that early resuscitation based on macrohemodynamic parameters does not prevent the development of organ dysfunction in a porcine model of endotoxemic shock, and that sublingual microcirculatory parameters are associated with markers of tissue metabolic stress and injury. Results: Both resuscitation groups had significant increases in creatinine and neutrophil gelatinase-associated lipocalin as compared with baseline. Neither the macrovascular response to endotoxemia or resuscitation, nor group allocation predicted the development of acute kidney injury (AKI). Only a microvascular flow index (MFI) <2.5 was associated with the development of renal tubular injury and AKI, and with increased renal, liver, peritoneal, and sublingual lactate/pyruvate (L/P) ratio and lactate. Among systemic parameters, only partial pressure of carbon dioxide (PCO2) gap >6 and P(a-v)CO2/C(v-a)O2 >1.8 were associated with increased organ L/P ratio and AKI. Innovation and Conclusion: Our findings demonstrate that targeting macrohemodynamics to guide resuscitation during endotoxemic shock failed to predict tissue metabolic stress and the response of the microvasculature to resuscitation, and was unsuccessful in preventing tubular injury and AKI. Mechanistically, our data suggest that loss of hemodynamic coherence and decoupling of microvascular flow from tissue metabolic demand during endotoxemia may explain the lack of association between macrohemodynamics and perfusion goals. Finally, we demonstrate that MFI, PCO2 gap, and P(v-a)CO2/C(a-v)O2 ratio outperformed macrohemodynamic parameters at predicting the development of renal metabolic stress and tubular injury, and therefore, that these indices merit further validation as promising resuscitation targets. Antioxid. Redox Signal. 35, 1407-1425.

POLG-Associated Ataxia Presenting as a Fragile X Tremor/Ataxia Phenocopy Syndrome.

Hyperintensities in the middle cerebellar peduncles (MCP), known as the MCP sign, and progressive late-onset ataxia constitute major characteristics of the fragile X tremor/ataxia syndrome (FXTAS). Here, we describe a 60-year-old male affected by ataxia due to biallelic mutations in the mitochondrial polymerase gamma (POLG) gene in which hyperintensities of the middle cerebellar peduncles (MCP) were found. The initial suspicion of FXTAS was however ruled out by a normal CGG expansion size in the FMR1 gene. We discuss the features of late-onset POLG-A as a phenocopy of FXTAS.

Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation.

AIMS: Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. RESULTS: Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). CONCLUSION: These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.

Inhaled, nebulized sodium nitrite protects in murine and porcine experimental models of hemorrhagic shock and resuscitation by limiting mitochondrial injury.

OBJECTIVE: The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. METHODS: Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90-120 min of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30 mg in 5 mL PBS). Pigs (30-35 kg) were anesthetized and bled to a MAP of 30-40 mmHg for 90 min, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 min into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. RESULTS: NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. CONCLUSION: NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury.

An adequately robust early TNF-alpha response is a hallmark of survival following trauma/hemorrhage.

BACKGROUND: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental. METHODOLOGY/PRINCIPAL FINDINGS: Paradoxically, plasma levels of the early inflammatory cytokine TNF-alpha (but not IL-6, IL-10, or NO(2) (-)/NO(3) (-)) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-alpha was inversely correlated with Marshall Score, an index of organ dysfunction, both in the 23 patients taken together and in the survivor cohort. Accordingly, we hypothesized that if an early, robust pro-inflammatory response were to be a marker of an appropriate response to injury, then individuals exhibiting such a response would be predisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetized pigs were subjected to T/HS (12 HS-only and 11 HS + Thoracotomy; mean arterial pressure of 30 mmHg for 45-90 min) along with surgery-only controls. Plasma obtained at pre-surgery, baseline post-surgery, beginning of HS, and every 15 min thereafter until 75 min (in the HS only group) or 90 min (in the HS + Thoracotomy group) was assayed for TNF-alpha, IL-6, IL-10, and NO(2) (-)/NO(3) (-). Mean post-surgery+/-HS TNF-alpha levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-alpha levels over the same interval. CONCLUSIONS/SIGNIFICANCE: Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-alpha. It is currently unclear if this response was the cause of this protection, a marker of survival, or both. This abstract won a Young Investigator Travel Award at the SHOCK 2008 meeting in Cologne, Germany.

Analysis of acuity trends using Resource Intensity Weights via the CIHI Portal.

One key to revolutionizing health care with informatics is the ability of decision-makers to access and analyze relevant data in a timely and efficient manner. Inspired by the demand for timely access to hospitalization data in Canada, CIHI Portal is an innovative web-based analytical tool which combines leading technology and data for decision support analysis. Hospitals, regional health authorities and ministries of health can use CIHI Portal to access comparable, pan-Canadian healthcare data for health data analysis, collaboration and dissemination. The goal of CIHI Portal is to support health care decision-makers in their local and regional health care planning and to answer service delivery questions.The Capital Health region in Alberta used Resource Intensity Weights (RIW) to investigate claims that patients within their region were getting sicker over the past few years and that additional resources would be required in the future. Using the CIHI Portal, Capital Health conducted an analysis on historical trends in the average RIWs Average Resource Intensity Weight is calculated as the total Resource Intensity Weight (RIW) divided by the total number of inpatient separations. and found that although typical patients were not using a greater amount of resources, there was definitely an increase in the amount of resources consumed by atypical patients. Information contained in the analysis influenced budgeting, fund reallocation and health care planning. CIHI Portal has proven to be a reliable tool for data access, information sharing and knowledge exchange. It has enhanced decision support services within the Capital Health region.

Self-efficacy and academic achievement in Australian high school students: the mediating effects of academic aspirations and delinquency.

Studies have shown that self-efficacy, aspirational, and other psychosocial influences account for considerable variance in academic achievement through a range of mediational pathways, although no research to date has tested the mediational relationships identified. The present research investigated the structural relations among self-efficacy, academic aspirations, and delinquency, on the academic achievement of 935 students aged 11-18 years from ten schools in two Australian cities. The Children's Self-Efficacy Scale, Adapted Self-Report Delinquency Scale (Revised), and Children's Academic Aspirations Scale were administered to participants prior to academic achievement being assessed using mid-year school grades. Structural equation modeling was employed to test three alternative models for the relationships from academic, social, and self-regulatory efficacy on academic achievement. A partial mediation model showed the best overall fit to the data. Academic and self-regulatory efficacy had an indirect negative effect through delinquency and a direct positive effect on academic achievement. Academic and social self-efficacy had positive and negative relationships, respectively, with academic aspiration and academic achievement; however, the relationship between academic aspiration and academic achievement was not significant in the final model.

Evaluation of a community health promotion resource for primary care practices.

BACKGROUND: Primary care physicians' ability to provide effective health behavior change advice might be leveraged by linking to available community resources. This study evaluates tools to facilitate such a link. DESIGN: A mixed methods longitudinal pre-post-test study was conducted in 2004. SETTING/ PARTICIPANTS: Seven primary care practices in northeast Ohio and two longitudinal cohorts of patients (n=784). INTERVENTION: The practice-tailored intervention included two main components: (1) a web-based health behavior change resource including a database of community programs and patient education materials, and (2) a health behavior prescription pad. MAIN OUTCOME MEASURES: Rates of discussion of diet, exercise, weight management, and smoking cessation; and patient change in motivation to modify behaviors at 8 weeks post-visit. Qualitative field notes about practice routines, culture, and implementation efforts were analyzed to enhance understanding of the practice change process. RESULTS: The post-intervention cohort reported higher rates of discussion of diet (25.7% vs 20.2%), exercise (27.8% vs 16.9%), and weight management (23.2% vs 16.3%), and greater referral to patient education materials (24.2% vs 21.6%) and community programs for health behavior change (16.0% vs 13.6%) (p<0.05). No difference in change in patient motivation to modify behavior was observed between the pre- and post-intervention cohorts. Evaluation of the qualitative field notes suggests that for six of seven practices, the intervention was not appreciably implemented. CONCLUSIONS: The intervention tools show promise for increasing clinician discussion of health behaviors, information referral, and referral to community resources. Additional work to increase practice adoption of the tools is required to understand their potential to affect patient motivation to change behavior.

Ethical parameters of challenge studies inducing psychosis with ketamine.

Researchers routinely induce psychosis in healthy volunteers via ketamine infusion to expand their knowledge of schizophrenia. We question the ethics of the nature and procedures of such studies. We also address safeguards for ethically conducting and reporting such pursuits, including recruitment, screening, available treatment, and follow-up.