IntroductionsuPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR), which is expressed in various immunologically active cells. High suPAR serum concentrations are suggested to reflect the activation of the immune system in circumstances of inflammation and infection, and have been associated with increased mortality in different populations of non-intensive care patients. In this study we sequentially analyzed suPAR serum concentrations within the first week of intensive care in a large cohort of well characterized intensive care unit (ICU) patients, in order to investigate potential regulatory mechanisms and evaluate the prognostic significance in critically ill patients.MethodsA total of 273 patients (197 with sepsis, 76 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU), on Day 3 and Day 7, and compared to 43 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately one year.ResultsUpon admission to the ICU suPAR serum concentrations were elevated in critically ill patients as compared with healthy controls. In sepsis patients suPAR levels were higher than in non-sepsis patients (with or without systemic inflammatory response syndrome (SIRS)). During the first week after admission to the ICU serum suPAR concentrations remained stably elevated. suPAR serum concentrations measured upon admission were closely and independently correlated to various laboratory parameters, specifically biomarkers of inflammation (tumor necrosis factor (TNF), C-reactive protein (CRP)), hepatic and renal dysfunction. High suPAR levels at admission and at Day 3 were a strong independent predictor for both ICU and long-term mortality in critically ill patients.ConclusionsIn sepsis and non-sepsis patients suPAR serum concentrations are increased upon admission to the ICU, likely reflecting the activation state of the immune system, and remain stably elevated in the initial course of treatment. Low suPAR levels are a positive predictor of ICU- and overall survival in critically ill patients, including sepsis and non-sepsis patients. Aside from its value as a promising new prognostic biomarker, both experimental and clinical studies are required in order to understand the specific effects and regulatory mechanisms of suPAR in SIRS and sepsis, and may reveal new therapeutic options.

Al-Fatly et al. establish predictive connectivity maps of deep brain stimulation in essential tremor. They demonstrate that electrode connectivity to tremor-associated brain areas can predict postoperative improvement and that these maps can be somatotopically segregated according to the tremor-affected body parts.

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IntroductionC-type natriuretic peptide (CNP) is a paracrine molecule which is mainly synthesized in the vasculature. High levels have been reported in sepsis, and CNP has been proposed as a biomarker predicting sepsis in traumatized patients. We aimed at evaluating the diagnostic and prognostic value of N-terminal pro-CNP (NT-proCNP) for predicting sepsis, disease severity and mortality in critically ill medical patients.Methods273 critically ill patients (197 patients with sepsis or septic shock, 76 without evidence of sepsis) and 43 healthy controls were consecutively included in a prospective clinical single-center non-interventional study at the Medical Intensive Care Unit, RWTH-University Aachen, Germany. Patients' outcome was followed for about 1 year. NT-proCNP serum concentrations were determined upon ICU admission, as well as in the mornings of day 3 and day 7 after admission. Intensive care treatment measures as well as routine and experimental laboratory parameters were recorded and analyzed.ResultsNT-proCNP serum concentrations upon admission to the ICU were elevated in critically ill patients as compared with healthy controls. Patients with sepsis had significantly higher NT-proCNP levels than non-sepsis patients. NT-proCNP was strongly associated with inflammatory parameters (i.e. C-reactive protein, procalcitonin and TNF-α), biomarkers of organ dysfunction and clinical composite scores (APACHE-II, SOFA, SAPS2). NT-proCNP levels at admission and day 3 were found to be a strong predictive marker for ICU- and overall survival. Moreover, a decline of serum NT-proCNP after admission to the ICU was associated with reduced mortality. The predictive power of serum NT-proCNP was similar to 'conventional' prognostic tools such as clinical scores.ConclusionsNT-proCNP is significantly elevated in critically ill patients, with highest levels in sepsis. Inflammation as well as organ function are strongly associated with NT-proCNP serum concentrations. Low initial NT-proCNP levels and a decline during initial treatment indicate a favourable ICU- and long-term outcome.

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IntroductionHepatic dysfunction is a common finding in critically ill patients on the ICU and directly influences survival. Liver stiffness can be measured by the novel method of transient elastography (fibroscan) and is closely associated with hepatic fibrosis in patients with chronic liver disease, but also is increased in patients with acute hepatitis, acute liver failure and cholestasis. We investigated liver stiffness as a potentially useful tool for early detection of patients with hepatic deterioration and risk stratification with respect to short- and long-term mortality.MethodsWe prospectively evaluated 108 consecutive critically ill patients at our medical intensive care unit (ICU) with subsequent longitudinal liver stiffness measurements (admission, Day 3, Day 7 and weekly thereafter) during the course of ICU treatment. Outcome was followed after discharge (median observation time 237 days).ResultsLiver stiffness could be reliably measured in 71% of ICU patients at admission (65% at Day 3, 63% at Day 7). Critically ill patients (n = 108) had significantly increased liver stiffness compared to sex- and age-matched standard care patients (n = 25). ICU patients with decompensated cirrhosis showed highest liver stiffness, whereas other critical diseases (for example, sepsis) and comorbidities (for example, diabetes, obesity) did not impact stiffness values. At admission to the ICU, liver stiffness is closely related to hepatic damage (liver synthesis, cholestasis, fibrosis markers). During the course of ICU treatment, fluid overload (renal failure, volume therapy) and increased central venous pressure (mechanical ventilation, heart failure) were major factors determining liver stiffness. Liver stiffness values > 18 kilopascal (kPa) at ICU admission were associated with increased ICU and long-term mortality, even in non-cirrhotic patients.ConclusionsConsidering that liver stiffness cannot be validly measured in about 30% of ICU patients, transient elastography performed at ICU admission might be a useful tool to early identify liver dysfunction and predict mortality in critically ill patients at a medical ICU.

BackgroundAllergic Rhinitis (AR) is a common disorder in Europe with Allergic Asthma (AA) as a frequent comorbidity. Allergy immunotherapy (AIT) is the only causal therapy of AR and AA, and can be administered as subcutaneous injections at the physician or as sublingual drops or tablets at home. The usual treatment duration is 3 years.ObjectiveThis study aimed to elicit patient preferences to identify the AIT administration mode preferred by patients.MethodsA discrete-choice-experiment (DCE) was developed to determine how people weight different treatment options using a paper-based questionnaire from June to September 2014, including 16 study centres. Main inclusion criteria: >18 years, grass, birch and/or house dust mite AR with moderate to severe symptoms, AIT-naïve and AIT-indicated. DCE-attributes were: Administration form, number and duration of physician visits, frequency of life-threatening anaphylactic shocks, local side-effects and co-payments.ResultsTwo-hundred thirty-nine subjects participated, resulting in analysable 1842 choices. All attributes were significant predictors for the treatment-choice. Ranked by importance, the following first three attributes are most preferred by patients:1st Number and duration of physician visits:Fewer visits with shorter duration preferred (0.658*)2nd Frequency of life-threatening anaphylactic shocks:Lower risk of shocks preferred (0.285*)3rd Local side-effects:Preference for rash/swelling on upper arm over itching/swelling under the tongue (0.210*)(*coefficient-size represents relative importance of the attributes)ConclusionThe most important attribute is the number and duration of visits to a physician. A lower risk of life-threatening anaphylactic shocks was ranked as the second whereas co-payments and administration form play a limited role.

Background and ObjectiveAllergy immunotherapy (AIT) with the SQ® grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious, well-tolerated and to improve disease-specific health-related quality of life (HRQoL) in controlled clinical trials. The aim of our study was to investigate HRQoL in patients with allergic rhinoconjunctivitis routinely treated with the SLIT-tablet and taking symptomatic medication as needed compared with patients treated only with symptomatic medication.MethodsIn a non-interventional, open-label study, patients treated with the SLIT-tablet were observed for about 12 months compared with patients only symptomatically treated. Patients assessed their HRQoL with the 12-Item Short Form Health Survey (SF-12) and the Rhinitis Quality of Life Questionnaire (RQLQ) in the grass pollen seasons (GPS) at baseline (GPS1, HRQoL1), after GPS1 (HRQoL2) and in the following GPS (GPS2, HRQoL3). Tolerability, compliance, symptoms and medication use were assessed in the SLIT-tablet group by the physician.ResultsOverall, data were analysed in 576 patients. Mean differences (±SD) in overall scores for HRQoL3 versus HRQoL1 (186 patients) of SF-12 were +11.4 ± 16.8 (SLIT-tablet) and −3.4 ± 15.7 (symptomatic medication), (p < 0.0001), and of RQLQ −1.31 ± 1.07 and +0.10 ± 0.74 (p < 0.001), and for HRQoL3 versus HRQoL2 (238 patients) of SF-12 −1.6 ± 15.3 and −10.0 ± 14.1 (p = 0.0003), and of RQLQ +0.22 ± 1.29 and +1.24 ± 1.30 (p < 0.0001). Tolerability and adherence for the SLIT-tablet were comparable with data of other non-interventional studies.ConclusionsRoutine treatment with the SQ® grass SLIT-tablet resulted in clear improvements in disease-specific and general quality of life, while no improvements were observed in patients treated only symptomatically.