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PurposeTo investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI).MethodsMulticenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality.Results339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80–1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0–2.2] days in the BDG group and 4.4 (IQR 2.0–9.1, p < 0.01) days in the control group.ConclusionsSerum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

A relief worker who became infected with the Ebola virus while working in Sierra Leone during the largest recorded Ebola epidemic was evacuated to Hamburg, Germany, for care. The details of his severe illness and response to supportive care are reported. Since December 2013, a Zaire ebolavirus (EBOV) epidemic of unprecedented scale has ravaged West Africa, with a focus on Guinea, Sierra Leone, and Liberia. 1 – 4 The current epidemic has led to a public health emergency in the region, exacerbated by high rates of infection among health care personnel. A substantial number of fatal cases are among health care workers. 2 Several international health care workers have been evacuated to specialized centers in Europe and the United States. The patient transferred to our isolation unit worked for the World Health Organization (WHO) as an epidemiologist in Sierra Leone and was airlifted at . . .

Laser-driven ion accelerators can deliver high-energy, high-peak current beams and are thus attracting attention as a compact alternative to conventional accelerators. However, achieving sufficiently high energy levels suitable for applications such as radiation therapy remains a challenge for laser-driven ion accelerators. Here we generate proton beams with a spectrally separated high-energy component of up to 150 MeV by irradiating solid-density plastic foil targets with ultrashort laser pulses from a repetitive petawatt laser. The preceding laser light heats the target, leading to the onset of relativistically induced transparency upon main pulse arrival. The laser peak then penetrates the initially opaque target and triggers proton acceleration through a cascade of different mechanisms, as revealed by three-dimensional particle-in-cell simulations. The transparency of the target can be used to identify the high-performance domain, making it a suitable feedback parameter for automated laser and target optimization to enhance stability of plasma accelerators in the future. Laser-driven proton acceleration experiments achieve energies of up to 150 MeV with particle yields that are relevant for applications such as radiobiology.

Laser plasma-based particle accelerators attract great interest in fields where conventional accelerators reach limits based on size, cost or beam parameters. Despite the fact that particle in cell simulations have predicted several advantageous ion acceleration schemes, laser accelerators have not yet reached their full potential in producing simultaneous high-radiation doses at high particle energies. The most stringent limitation is the lack of a suitable high-repetition rate target that also provides a high degree of control of the plasma conditions required to access these advanced regimes. Here, we demonstrate that the interaction of petawatt-class laser pulses with a pre-formed micrometer-sized cryogenic hydrogen jet plasma overcomes these limitations enabling tailored density scans from the solid to the underdense regime. Our proof-of-concept experiment demonstrates that the near-critical plasma density profile produces proton energies of up to 80 MeV. Based on hydrodynamic and three-dimensional particle in cell simulations, transition between different acceleration schemes are shown, suggesting enhanced proton acceleration at the relativistic transparency front for the optimal case. Laser-produced plasma can be used for particle acceleration in different schemes. Here the authors demonstrate proton acceleration from the intense ultrashort laser pulse interaction with micron-sized cryogenic hydrogen jet.

Background Sepsis is a serious disease condition and a major cause of intensive care unit (ICU) admission. Its diagnosis in critically ill patients is complicated. To diagnose an infection rapidly, and to accurately differentiate systemic inflammatory response syndrome (SIRS) from sepsis, is challenging yet early diagnosis is vital for early induction of an appropriate therapy. The aim of this study was to evaluate whether the immature granulocyte (IG) count is a useful early diagnostic marker of sepsis compared to other markers. Therefore, a total of 70 consecutive surgical intensive care patients were assessed. IGs were measured from whole blood samples using an automated analyzer. C-reactive protein (CRP), lipopolysaccharide binding protein (LBP) and interleukin-6 (IL-6) concentrations were also determined. The observation period was a maximum of 21 days and ended with the patients’ discharge from ICU or death. Receiver operating characteristic (ROC) analyses were conducted and area under the curve (AUC) was calculated to determine sensitivities and specificities for the parameters. Results We found that the IG count significantly discriminates between infected and non-infected patients ( P  < 0.0001) with a sensitivity of 89.2% and a specificity of 76.4%, particularly within the first 48 hours after SIRS onset. Regarding the discriminative power for infection, the IG count was more indicative than other clinical parameters such as CRP, LBP and IL-6, which had a sensitivity of less than 68%. Additionally, the highest diagnostic odds ratio (DOR) with 26.7 was calculated for the IG count within the first 48 hours. During the course of the disease ROC curve analyses showed a superior positive predictive value of the IG count compared to the other measured parameters during the first five days following the fulfillment of SIRS criteria. However, the number of IGs was not correlated with ICU mortality. Conclusions The total number of IG in peripheral blood from ICU patients is a good marker to discriminate infected and non-infected patients very early during SIRS. However, the IG count is not suitable as a prognostic marker for mortality. Routine and serial measurement of IGs may provide new possibilities for rapid screening of SIRS patients on ICU with suspected infections.

Introduction The aim of the study was to evaluate the feasibility and safety of avoiding invasive mechanical ventilation (IMV) by using extracorporeal CO 2 removal (ECCO 2 R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure refractory to noninvasive ventilation (NIV). Methods Case–control study. Patients with acute hypercapnic respiratory failure refractory to NIV being treated with a pump-driven veno-venous ECCO 2 R system (iLA-Activve ® ; Novalung, Heilbronn, Germany) were prospectively observed in five European intensive care units (ICU). Inclusion criteria were respiratory acidosis (pH ≤ 7.35, PaCO 2  > 45 mmHg) with predefined criteria for endotracheal intubation (ClinicalTrials.gov NCT01784367). The historical controls were patients with acute hypercapnic respiratory failure refractory to NIV who were treated with IMV. The matching criteria were main diagnosis, age, SAPS-II score and pH. Results Twenty-five cases (48.0 % male, mean age 67.3 years) were matched with 25 controls. Intubation was avoided in 14 patients (56.0 %) in the ECCO 2 R group with a mean extracorporeal blood flow of 1.3 L/min. Seven patients were intubated because of progressive hypoxaemia and four owing to ventilatory failure despite ECCO 2 R and NIV. Relevant ECCO 2 R-associated adverse events were observed in 11 patients (44.0 %), of whom 9 (36.0 %) suffered major bleeding complications. The mean time on IMV, ICU stay and hospital stay in the case and control groups were 8.3 vs. 13.7, 28.9 vs. 24.0 and 36.9 vs. 37.0 days, respectively, and the 90-day mortality rates were 28.0 vs. 28.0 %. Conclusions The use of veno-venous ECCO 2 R to avoid invasive mechanical ventilation was successful in just over half of the cases. However, relevant ECCO 2 R-associated complications occurred in over one-third of cases. Despite the shorter period of IMV in the ECCO 2 R group there were no significant differences in length of stay or in 28- and 90-day mortality rates between the two groups. Larger, randomised studies are warranted for further assessment of the effectiveness of ECCO 2 R.

Background The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED). Methods Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration ( f T > MIC ) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa . Results A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC ) and susceptible P. aeruginosa (MIC ≤ 2 mg/L) was > 95% for a dose of 0.5 g 8-hourly. In patients with a residual diuresis of 300 mL/d 1 g 12-hourly and 2 g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC , respectively. A dose of 2 g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis. Conclusions We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing. Trial registration Clincialtrials.gov, NCT02287493 .

Background Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of checklists may be an additional tool to improve the effect of these bundles even in highly specialized institutions. In this study we investigate if the introduction of a checklist reduces the frequency of CLABSI. Methods During the study period from October 2011 to September 2012, we investigated the effect of implementing a checklist for the placement of central venous lines (CVL). Patients were allocated either to the checklist group or to the control group, roughly in a 1:2 ratio. The frequency of CLABSI was compared between the two groups. Results During the study period 4416 CVL were inserted; 1518 in the checklist group and 2898 in the control group. The use of the checklist during CVL placement resulted in a lower CLABSI frequency. The incidence in the checklist group was 3.8 per 1000 catheter days as compared to 5.9 per 1000 catheter days in the control group (IRR = 0.57; p  = 0.001). The use of the checklist also reduced the frequency of catheter colonisation significantly, 36.3 per 1000 catheter days in the checklist group vs 21.2 per 1000 catheter days in the control group, respectively (IRR = 0.58; p  < 0.001). Conclusion The introduction of a checklist to improve the adherence to hygiene standards while placement of central venous lines reduced the frequency of infections significantly.