Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation.

AbstractBackgroundCardiopulmonary bypass induces a systemic inflammatory response that may contribute to clinical morbidity. Gaseous nitric oxide at relatively low concentrations may elicit peripheral anti-inflammatory effects in addition to a reduction of pulmonary resistances. We examined the effects of 20 ppm of inhaled nitric oxide administered for 8 hours during and after cardiopulmonary bypass.Methods and resultsTwenty-nine consecutive patients undergoing aortic valve replacement combined with aortocoronary bypass were randomly allocated to either 20 ppm of inhaled nitric oxide (n = 14) or no additional inhalatory treatment (n = 15). Blood samples for total creatine kinase, creatine kinase MB fraction, and troponin I measurements were collected at 4, 12, 24, and 48 hours postsurgery. In addition, we collected perioperative blood samples for measurements of circulating nitric oxide by-products and brain natriuretic peptide. Soluble P-selectin was analyzed in blood samples withdrawn from the coronary sinus before and after aortic clamping. The area under the curve of creatine kinase MB fraction (P = .03), total creatine kinase (P = .04), and troponin I (P = .04) levels were significantly decreased in the nitric oxide–treated patients. Moreover, in the same group we observed blunted P-selectin and brain natriuretic peptide release (P = .01 and P = .02, respectively). Nitric oxide inhalation consistently enhanced nitric oxide metabolite levels (P = .01).ConclusionsNitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties

Randomized Evidence for Reduction of Perioperative Mortality.

Objective: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. Design and Setting: A web-based international consensus conference. Participants: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. Interventions: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. Measurements and Main Results: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. Conclusions: Future research and health care funding should be directed toward studying and evaluating these interventions

Reducing mortality in acute kidney injury patients: systematic review and international web-based survey

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics

Randomized Evidence for Reduction of Perioperative Mortality

Objective: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. Design and Setting: A web-based international consensus conference. Participants: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. Interventions: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. Measurements and Main Results: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. Conclusions: Future research and health care funding should be directed toward studying and evaluating these interventions. © 2012 Elsevier Inc

Randomized Evidence for Reduction of Perioperative Mortality

Objective: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. Design and Setting: A web-based international consensus conference. Participants: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. Interventions: Systematic literature searches (MEDLINE/Pub Med, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. Measurements and Main Results: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. Conclusions: Future research and health care funding should be directed toward studying and evaluating these interventions

Regular Wine Consumption in Chronic Heart Failure: Impact on Outcomes, Quality of Life, and Circulating Biomarkers

Background-Moderate, regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce. We evaluated the relations between wine consumption, health status, circulating biomarkers, and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial. Methods and Results-A brief questionnaire on dietary habits was administered at baseline to 6973 patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial. The relations between wine consumption, fatal and nonfatal clinical end points, quality of life, symptoms of depression, and circulating biomarkers of cardiac function and inflammation (in subsets of patients) were evaluated with simple and multivariable-adjusted statistical models. Almost 56% of the patients reported drinking at least 1 glass of wine per day. After adjustment, clinical outcomes were not significantly different in the predefined 4 groups of wine consumption. However, patients with more frequent wine consumption had a significantly better perception of health status (Kansas City Cardiomyopathy Questionnaire score, adjusted P<0.0001), less frequent symptoms of depression (Geriatric Depression Scale, adjusted P=0.01), and lower plasma levels of biomarkers of vascular inflammation (osteoprotegerin and C-terminal proendothelin-1, adjusted P<0.0001, and pentraxin-3, P=0.01) after adjusting for possible confounders. Conclusions-We show for the first time in a large cohort of patients with chronic heart failure that moderate wine consumption is associated with a better perceived and objective health status, lower prevalence of depression, and less vascular inflammation, but does not translate into more favorable clinical 4-year outcomes. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT0033633

Overview of JET results for optimising ITER operation

The JET 2019-2020 scientific and technological programme exploited the results of years of concerted scientific and engineering work, including the ITER-like wall (ILW: Be wall and W divertor) installed in 2010, improved diagnostic capabilities now fully available, a major neutral beam injection upgrade providing record power in 2019-2020, and tested the technical and procedural preparation for safe operation with tritium. Research along three complementary axes yielded a wealth of new results. Firstly, the JET plasma programme delivered scenarios suitable for high fusion power and alpha particle (alpha) physics in the coming D-T campaign (DTE2), with record sustained neutron rates, as well as plasmas for clarifying the impact of isotope mass on plasma core, edge and plasma-wall interactions, and for ITER pre-fusion power operation. The efficacy of the newly installed shattered pellet injector for mitigating disruption forces and runaway electrons was demonstrated. Secondly, research on the consequences of long-term exposure to JET-ILW plasma was completed, with emphasis on wall damage and fuel retention, and with analyses of wall materials and dust particles that will help validate assumptions and codes for design and operation of ITER and DEMO. Thirdly, the nuclear technology programme aiming to deliver maximum technological return from operations in D, T and D-T benefited from the highest D-D neutron yield in years, securing results for validating radiation transport and activation codes, and nuclear data for ITER

Experimental study on the role of the target electron temperature as a key parameter linking recycling to plasma performance in JET-ILW*

Changes in global and edge plasma parameters (H (98(y,2)), dimensionless collisionality nu *, core density peaking, separatrix density n (e,sep)) with variations in the D-2 fueling rate and divertor configuration are unified into a single trend when mapped to ⟨T (e,ot)⟩, the spatially averaged spectroscopically derived outer target electron temperature. Dedicated JET with the ITER-like wall (JET-ILW) experiments in combination with an extended JET-ILW database of unseeded low-triangularity H-mode plasmas spanning a wide range of D-2 fueling rates, I (p), B (t) and heating power have demonstrated the importance of ⟨T (e,ot)⟩ as a key physics parameter linking the recycling particle source and detachment with plasma performance. The remarkably robust H (98(y,2)) trend with ⟨T (e,ot)⟩ is connected to a strong inverse correlation between ⟨T (e,ot)⟩, n (e,sep) and nu *, thus directly linking changes in the divertor recycling moderated by ⟨T (e,ot)⟩ with the previously established relationship between nu *, core density peaking and core pressure resulting in a degradation in core plasma performance with decreasing ⟨T (e,ot)⟩ (increasing nu *). A strong inverse correlation between the separatrix to pedestal density ratio, n (e,sep)/n (e,ped), and ⟨T (e,ot)⟩ is also established, with the rise in n (e,sep)/n (e,ped) saturating at ⟨T (e,ot)⟩ > 10 eV. A strong reduction in H (98(y,2)) is observed as ⟨T (e,ot)⟩ is driven from 30 to 10 eV via additional D-2 gas fueling, while the divertor remains attached. Consequently, the pronounced performance degradation in attached divertor conditions has implications for impurity seeding radiative divertor scenarios, in which H (98(y,2)) is already low (similar to 0.7) before impurities are injected into the plasma since moderate gas fueling rates are required to promote high divertor neutral pressure. A favorable pedestal pressure, p (e,ped), dependence on I (p) has also been observed, with an overall increase in p (e,ped) at I (p) = 3.4 MA as ⟨T (e,ot)⟩ is driven down from attached to high-recycling divertor conditions. In contrast, p (e,ped) is reduced with decreasing ⟨T (e,ot)⟩ in the lower I (p) branches. Further work is needed to (i) clarify the potential role of edge opacity on the observed favorable pedestal pressure I (p) scaling; as well as to (ii) project the global and edge plasma performance trends with ⟨T (e,ot)⟩ to reactor-scale devices to improve predictive capability of the coupling between recycling and confined plasma fueling in what are foreseen to be more opaque edge plasma conditions