Active fluid de-resuscitation in critically ill patients with septic shock: A systematic review and meta-analysis.

PURPOSE To evaluate the impact of active fluid de-resuscitation on mortality in critically ill patients with septic shock. METHODS A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. Trials investigating active fluid de-resuscitation and reporting data on mortality in patients with septic shock were eligible. The primary objective was the impact of active de-resuscitation in patients with septic shock on short-term mortality. Secondary outcomes were whether de-resuscitation lead to a fluid separation, and the impact of de-resuscitation on patient-centred outcomes. RESULTS Thirteen trials (8,030 patients) were included in the systematic review, whereof 5 randomised-controlled trials (RCTs) were included in the meta-analysis. None of the RCTs showed a reduction in mortality with active de-resuscitation measures (relative risk (RR) 1.12 [95%-CI 0.84 - 1.48]). Fluid separation was achieved by two RCTs. Evidence from non-randomised trials suggests a mortality benefit with de-resuscitation strategies and indicates a trend towards a more negative fluid balance. Patient-centred outcomes were not influenced in the RCTs, and only one non-randomised trial revealed an impact on the duration of mechanical ventilation and renal replacement requirement (RRT). CONCLUSION We found no evidence for superiority of active fluid de-resuscitation compared to usual care regarding mortality, fluid balance or patient-centred outcomes in patients with septic shock. Current evidence is limited by the lack of high-quality RCTs in patients with septic shock, the small sample sizes and the heterogeneity of the applied de-resuscitation techniques. In addition, validity of the majority of RCTs is compromised by their inability to achieve fluid separation

Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model

Radiation-induced lymphopenia is a common occurrence in radiation oncology and an established negative prognostic factor, however the mechanisms underlying the relationship between lymphopenia and inferior survival remain elusive. The relevance of lymphocyte co-irradiation as critical normal tissue component at risk is an emerging topic of high clinical relevance, even more so in the context of potentially synergistic radiotherapy-immunotherapy combinations. The impact of the radiotherapy treatment volume on the lymphocytes of healthy and tumor-bearing mice was investigated in a novel mouse model of radiation-induced lymphopenia. Using an image-guided small-animal radiotherapy treatment platform, translationally relevant tumor-oriented volumes of irradiation with an anatomically defined increasing amount of normal tissue were irradiated, with a focus on the circulating blood and lymph nodes. In healthy mice, the influence of irradiation with increasing radiotherapy treatment volumes was quantified on the level of circulating blood cells and in the spleen. A significant decrease in the lymphocytes was observed in response to irradiation, including the minimally irradiated putative tumor area. The extent of lymphopenia correlated with the increasing volumes of irradiation. In tumor-bearing mice, differential radiotherapy treatment volumes did not influence the overall therapeutic response to radiotherapy alone. Intriguingly, an improved treatment efficacy in mice treated with draining-lymph node co-irradiation was observed in combination with an immune checkpoint inhibitor. Taken together, our study reveals compelling data on the importance of radiotherapy treatment volume in the context of lymphocytes as critical components of normal tissue co-irradiation and highlights emerging challenges at the interface of radiotherapy and immunotherapy. Keywords: Image-guided small animal radiotherapy platform; Lymphopenia; Normal tissue injury; Radioimmunotherapy; Radiotherap

Structure and morphology of low mechanical loss TiO₂-doped Ta₂O₅

The exceptional stability required from high finesse optical cavities and high precision interferometers is fundamentally limited by Brownian motion noise in the interference coatings of the cavity mirrors. In amorphous oxide coatings these thermally driven fluctuations are dominant in the high index layer compared to those in the low index SiO₂ layer in the stack. We present a systematic study of the evolution of the structural and optical properties of ion beam sputtered TiO₂-doped Ta₂O₅ films with annealing temperature. We show that low mechanical loss in TiO₂-doped Ta₂O₅ with a Ti cation ratio = 0.27 is associated with a material that consists of a homogeneous titanium-tantalum-oxygen mixture containing a low density of nanometer sized Ar-filled voids. When the Ti cation ratio is 0.53, phase separation occurs leading to increased mechanical loss. These results suggest that amorphous mixed oxides with low mechanical loss could be identified by considering the thermodynamics of ternary phase formation

Structure and morphology of low mechanical loss TiO₂-doped Ta₂O₅

The exceptional stability required from high finesse optical cavities and high precision interferometers is fundamentally limited by Brownian motion noise in the interference coatings of the cavity mirrors. In amorphous oxide coatings these thermally driven fluctuations are dominant in the high index layer compared to those in the low index SiO₂ layer in the stack. We present a systematic study of the evolution of the structural and optical properties of ion beam sputtered TiO₂-doped Ta₂O₅ films with annealing temperature. We show that low mechanical loss in TiO₂-doped Ta₂O₅ with a Ti cation ratio = 0.27 is associated with a material that consists of a homogeneous titanium-tantalum-oxygen mixture containing a low density of nanometer sized Ar-filled voids. When the Ti cation ratio is 0.53, phase separation occurs leading to increased mechanical loss. These results suggest that amorphous mixed oxides with low mechanical loss could be identified by considering the thermodynamics of ternary phase formation

Investigation of effects of assisted ion bombardment on mechanical loss of sputtered tantala thin films for gravitational wave interferometers

Reduction of Brownian thermal noise due to mechanical loss in high-reflectivity mirror coatings is critical for improving the sensitivity of future gravitational wave detectors. In these mirrors, the mechanical loss at room temperature is dominated by the high refractive index component, amorphous tantala (Ta₂O₅) or tantala doped with titania (Ti∶Ta₂O₅). Toward the goal of identifying mechanisms that could alter mechanical loss, this work investigates the use of assist ion bombardment in the reactive ion beam sputtering deposition of tantala single layers. Low-energy assist ion bombardment can enhance adatom diffusion. Low-energy assist Ar⁺ and Xe⁺ ion bombardment at different conditions was implemented during deposition to identify trends in the mechanical loss with ion mass, ion energy, and ion dose. It is shown that the atomic structure and bonding states of the tantala thin films are not significantly modified by low-energy assist ion bombardment. The coatings mechanical loss remains unaltered by ion bombardment within errors. Based on an analysis of surface diffusivity, it is shown that the dominant deposition of tantala clusters and limited surface diffusion length of oxygen atoms constrain structural changes in the tantala films. A slower deposition rate coupled with a significant increase in the dose of the low-energy assist ions may provide more favorable conditions to improve adatom diffusivity

Structural Evolution that Affects the Room-Temperature Internal Friction of Binary Oxide Nanolaminates: Implications for Ultrastable Optical Cavities

Internal friction in oxide thin films imposes a critical limitation to the sensitivity and stability of the ultrahigh finesse optical cavities for gravitational wave detectors. Strategies like doping or creating nanolaminates (NL) are sought to introduce structural modifications that reduce internal friction. This work describes an investigation of the morphological changes SiO₂/Ta₂O₅ and TiO₂/Ta₂O₅ nanolaminates undergo with annealing and their impact on room-temperature internal friction. It is demonstrated that thermal treatment results in a reduction of internal friction in both nanolaminates but through different pathways. In the SiO₂/Ta₂O₅ nanolaminate, the layers of which remain intact after annealing, the total reduction in internal friction follows the reduction in the composing SiO₂ and Ta₂O₅ layers. In contrast, interdiffusion initiated by annealing at the interface in the TiO₂/Ta₂O₅ nanolaminate leads to the formation of a mixed phase. It is the interfacial reaction upon annealing that dictates the more significant reduction in internal friction to ∼2.6 × 10⁻⁴, a value lower than any other Ta₂O₅ mixture coating with similar cation concentration