Comparison of bedside measurement of cardiac output with the thermodilution method and the Fick method in mechanically ventilated patients

INTRODUCTION: Bedside cardiac output determination is a common preoccupation in the critically ill. All available methods have drawbacks. We wished to re-examine the agreement between cardiac output determined using the thermodilution method (QTTHERM) and cardiac output determined using the metabolic (Fick) method (QTFICK) in patients with extremely severe states, all the more so in the context of changing practices in the management of patients. Indeed, the interchangeability of the methods is a clinically relevant question; for instance, in view of the debate about the risk–benefit balance of right heart catheterization. PATIENTS AND METHODS: Eighteen mechanically ventilated passive patients with a right heart catheter in place were studied (six women, 12 men; age, 39–84 years; simplified acute physiology scoreII, 39–111). QTTHERM was obtained using a standard procedure. QTFICK was measured from oxygen consumption, carbon dioxide production, and arterial and mixed venous oxygen contents. Forty-nine steady-state pairs of measurements were performed. The data were normalized for repeated measurements, and were tested for correlation and agreement. RESULTS: The QTFICK value was 5.2 ± 2.0 l/min whereas that of QTTHERM was 5.8 ± 1.9 l/min (R = 0.840, P < 0.0001; mean difference, -0.7 l/min; lower limit of agreement, -2.8 l/min; upper limit of agreement, 1.5 l/min). The agreement was excellent between the two techniques at QTTHERM values <5 l/min but became too loose for clinical interchangeability above this value. Tricuspid regurgitation did not influence the results. DISCUSSION AND CONCLUSIONS: No gold standard is established to measure cardiac output in critically ill patients. The thermodilution method has known limitations that can lead to inaccuracies. The metabolic method also has potential pitfalls in this context, particularly if there is increased oxygen consumption within the lungs. The concordance between the two methods for low cardiac output values suggests that they can both be relied upon for clinical decision making in this context. Conversely, a high cardiac output value is more difficult to rely on in absolute terms

Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans

BACKGROUND: Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation. RESULTS: Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH(2)O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20: -0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs. CONCLUSION: Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans

Differential Changes in QTc Duration during In-Hospital Haloperidol Use

Aims: To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. Methods: In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. Results: Patients with normal before-haloperidol QTc duration (male <= 430 ms, female <= 450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male >= 450 ms, female >= 470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR(adj) 34.9, p = 0.009) and before-haloperidol QTc duration (OR(adj) 0.94, p = 0.004). Conclusion: QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongatio

Moving toward the low-carbon hydrogen economy: experiences and key learnings from national case studies

The urgency to achieve net-zero carbon dioxide (CO2) emissions by 2050, as first presented by the IPCC special report on 1.5 °C Global Warming, has spurred renewed interest in hydrogen, to complement electrification, for widespread decarbonization of the economy. We present reflections on estimates of future hydrogen demand, optimization of infrastructure for hydrogen production, transport and storage, development of viable business cases, and environmental impact evaluations using life cycle assessments. We highlight challenges and opportunities that are common across studies of the business cases for hydrogen in Germany, the UK, the Netherlands, Switzerland and Norway. The use of hydrogen in the industrial sector is an important driver and could incentivise large-scale hydrogen value chains. In the long-term hydrogen becomes important also for the transport sector. Hydrogen production from natural gas with capture and permanent storage of the produced CO2 (CCS) enables large-scale hydrogen production in the intermediate future and is complementary to hydrogen from renewable power. Furthermore, timely establishment of hydrogen and CO2 infrastructures serves as an anchor to support the deployment of carbon dioxide removal technologies, such as direct air carbon capture and storage (DACCS) and biohydrogen production with CCS. Significant public support is needed to ensure coordinated planning, governance, and the establishment of supportive regulatory frameworks which foster the growth of hydrogen markets

The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell–intrinsic fashion and suppresses CNS autoimmunity

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-β/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor–related orphan receptor γt (RORγt). We identify the nuclear receptor peroxisome proliferator–activated receptor γ (PPARγ) as a key negative regulator of human and mouse Th17 differentiation. PPARγ activation in CD4+ T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPARγ involved inhibition of TGF-β/IL-6–induced expression of RORγt in T cells. Pharmacologic activation of PPARγ prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the RORγt promoter in T cells, thus interfering with RORγt transcription. Both T cell–specific PPARγ knockout and endogenous ligand activation revealed the physiological role of PPARγ for continuous T cell–intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4+ T cells from healthy controls and MS patients were strongly susceptible to PPARγ-mediated suppression of Th17 differentiation. In summary, we report a PPARγ-mediated T cell–intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPARγ represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS

Legionella Infection Risk from Domestic Hot Water

We investigated Legionella and Pseudomonas contamination of hot water in a cross-sectional multicentric survey in Italy. Chemical parameters (hardness, free chlorine, and trace elements) were determined. Legionella spp. were detected in 33 (22.6%) and Pseudomonas spp. in 56 (38.4%) of 146 samples. Some factors associated with Legionella contamination were heater type, tank distance and capacity, water plant age, and mineral content. Pseudomonas presence was influenced by water source, hardness, free chlorine, and temperature. Legionella contamination was associated with a centralized heater, distance from the heater point >10 m, and a water plant >10 years old. Furthermore, zinc levels of <20 μg/L and copper levels of >50 μg/L appeared to be protective against Legionella colonization. Legionella species and serogroups were differently distributed according to heater type, water temperature, and free chlorine, suggesting that Legionella strains may have a different sensibility and resistance to environmental factors and different ecologic niches