Soluble urokinase plasminogen activator receptor (suPAR) in bronchoalveolar fluid and blood in critically ill patients-a prospective cohort study.

INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. METHODS: We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. RESULTS: Seventy-five patients were available for analyses. Median age was 60 [25th-75th percentile: 50-69] years, 27% were female, and median SOFA score was 12 [11-14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0-17.2] ng/mL compared to those without ARDS at 7.1 [3.7-10.1] (p < 0.001). BALF-suPAR was significantly higher in patients with evidence of fungal lung infection compared to patients without fungal infection both in the general cohort (7.6 [3.2-9.4] vs 2.5 [1.1-5.3], p = 0.013) and in the subgroup of ARDS (7.2 [3.1-39.2] vs 2.5 [1.0-5.2], p = 0.022). All patients were classified as putative/probable invasive aspergillosis. CONCLUSION: We found significant higher levels of serum suPAR in ARDS patients compared to those not fulfilling ARDS criteria. Serum and BALF-suPAR were significantly higher in those patients with evidence for invasive pulmonary aspergillosis. These findings may suggest testing this biomarker for early diagnosis of fungal infection in a greater cohort.

Salivary potassium measured by genetically encoded potassium ion indicators as a surrogate for plasma potassium levels in hemodialysis patients-a proof-of-concept study.

BACKGROUND: Hyperkalemia is a common complication in cardiorenal patients treated with agents interfering with renal potassium (K+) excretion. It frequently leads to discontinuation of potentially life-saving medication, which has increased the importance of K+ monitoring. Non-invasive means to detect hyperkalemia are currently unavailable, but would be of potential use for therapy guidance. The aim of the present study was to assess the analytical performance of genetically encoded potassium-ion indicators (GEPIIs) in measuring salivary [K+] ([K+]Saliva) and to determine whether changes of [K+]Saliva depict those of [K+]Plasma. METHODS: We conducted this proof-of-concept study: saliva samples from 20 healthy volunteers as well as plasma and saliva from 29 patients on hemodialysis (HD) before and after three consecutive HD treatments were collected. We compared [K+]Saliva as assessed by the gold standard ion-selective electrode (ISE) with GEPII measurements. RESULTS: The Bland-Altmann analysis showed a strong agreement (bias 0.71; 95% limits of agreement from -2.79 to 4.40) between GEPII and ISE. Before treatment, patients on HD showed significantly higher [K+]Saliva compared with healthy controls [median 37.7 (30.85; 48.46) vs 23.8 (21.63; 25.23) mmol/L; P < .05]. [K+]Plasma in HD patients decreased significantly after dialysis. This was paralleled by a significant decrease in [K+]Saliva, and both parameters increased until the subsequent HD session. Despite similar kinetics, we found weak or no correlation between [K+]Plasma and [K+]Saliva. CONCLUSION: GEPIIs have shown an excellent performance in determining [K+]Saliva. [K+]Plasma and [K+]Saliva exhibited similar kinetics. To determine whether saliva could be a suitable sample type to monitor [K+]Plasma, further testing in future studies are required.

Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies.

OBJECTIVES: Anti-nucleocapsid (NC) antibodies are produced in response to SARS-CoV-2 infection. Therefore, they are well suited for the detection of a previous infection. Especially in the case of seroprevalence studies or during the evaluation of a novel in-vitro diagnostic test, samples have been stored at <-70 °C (short- and long-term) or 2-10 °C (short-term) before analysis. This study aimed to assess the impact of different storage conditions relevant to routine biobanking on anti-NC antibodies. METHODS: The preanalytical impact of short-term storage (84 [58-98] days) on <-70 °C and for 14 days at 2-10 °C was evaluated using samples from 111 donors of the MedUni Vienna Biobank. Long-term effects (443 [409-468] days) were assessed using 208 samples from Biobank Graz and 49 samples from Biobank Vienna. Anti-Nucleocapsid antibodies were measured employing electrochemiluminescence assays (Roche Anti-SARS-CoV-2). RESULTS: After short-term storage, the observed changes did not exceed the extent that could be explained by analytical variability. In contrast, results after long-term storage were approximately 20% higher and seemed to increase with storage duration. This effect was independent of the biobank from which the samples were obtained. Accordingly, the sensitivity increased from 92.6 to 95.3% (p=0.008). However, comparisons with data from Anti-Spike protein assays, where these deviations were not apparent, suggest that this deviation could also be explained by the analytical variability of the qualitative Anti-NC assay. CONCLUSIONS: Results from anti-NC antibodies are stable during short-term storage at <-70 °C and 2-10 °C. After long-term storage, a slight increase in sensitivity could not be ruled out.

Glucagon-Like Peptide-1 Receptor Agonism Improves Nephrotoxic Serum Nephritis by Inhibiting T-Cell Proliferation.

Glucagon-like peptide (GLP)-1 analogs such as liraglutide improved albuminuria in patients with type 2 diabetes in large randomized controlled trials. One of the suspected mechanisms is the anti-inflammatory potential of GLP-1 receptor (Glp1r) agonism. Thus, the anti-inflammatory action of Glp1r agonism was tested in a nondiabetic, T-cell-mediated murine model of nephrotoxic serum nephritis (NTS). The role of Glp1r in NTS was evaluated by using Glp1r-/- mice or C57BL/6 mice treated with liraglutide. In vitro, murine T cells were stimulated in the presence of liraglutide or vehicle. Glp1r-/- mice displayed increased renal infiltration of neutrophils and T cells after induction of NTS. Splenocyte proliferation and TH1 cytokine transcription were increased in spleen and lymph nodes of Glp1r-/- mice. Liraglutide treatment significantly improved the renal outcome of NTS in C57BL/6 mice by decreasing renal infiltration and proliferation of T cells, which resulted in decreased macrophage infiltration. In vitro, T cells stimulated in the presence of liraglutide showed decreased proliferation of TH1 and TH17 cells. Liraglutide blocked glycolysis in T cells and decreased their Glut1 mRNA expression. Together, Glp1r agonism protects mice from a T-cell-dependent glomerulonephritis model by inhibition of T-cell proliferation, possibly by interacting with their metabolic program. This mechanism may explain in part the renoprotective effects of Glp1r agonism in diabetic nephropathy.

Levels of interleukin (IL)-6 and IL-8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis.

Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at -70°C for retrospective determination of cytokines. IL-6 and IL-8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL-10 (P = .059). In multivariate conditional logistic regression analysis, IL-10 remained a significant predictor of IPA in serum and IL-8 among BALF cytokines. In conclusion, levels of IL-6 and IL-8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL-10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.

Soluble Urokinase Plasminogen Activator Receptor (SuPAR) Analysis for Diagnosis of Periprosthetic Joint Infection.

Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden's J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated.

Effects of Different Types of Intermittent Fasting Interventions on Metabolic Health in Healthy Individuals (EDIF): A Randomised Trial with a Controlled-Run in Phase.

The effects of intermittent fasting (IF) on health promotion in the healthy population remain controversial. Therefore, our study aimed to analyse the efficacy and feasibility of different IF protocols and evaluated the effects within a cohort with a controlled-run in phase on the body mass index (BMI) as the primary outcome, the body composition, and metabolic and haematological markers in healthy participants. A total of 25 individuals were randomised into three fasting groups: 16/8 fasting (n = 11), 20/4 fasting (n = 6), and alternate-day fasting (ADF, n = 8). Assessments were conducted at baseline (visit 1), after a four-week controlled-run in phase (visit 2), and after eight weeks of fasting (visit 3). Both the BMI (p = 0.01) and bodyweight (p = 0.01) were significantly reduced in the ADF group, which was not seen in the 16/8 and 20/4 groups (p > 0.05). Adherence was different but not statistically among the groups (16/8: 84.5 ± 23.0%; 20/4: 92.7 ± 9.5%; and ADF: 78.1 ± 33.5%, p = 0.57). Based on our obtained results, the data suggest that some fasting interventions might be promising for metabolic health. However, adherence to the specific fasting protocols remains challenging even for the healthy population.

Vancomycin Elution Kinetics of Four Antibiotic Carriers Used in Orthopaedic Surgery: In Vitro Study over 42 Days.

This study aimed to analyse and compare the vancomycin elution kinetics of four biodegradable, osteoconductive antibiotic carriers used in clinical practice within a 42-day in vitro setting. Carriers A and D already contained vancomycin (1.1 g and 0.247 g), whereas carriers B and C were mixed with vancomycin according to the manufacturer's recommendations (B: 0.83 g and C: 0.305 g). At nine time points, 50% (4.5 mL) of the elution sample was removed and substituted with the same amount of PBS. Probes were analysed with a kinetic microparticle immunoassay. Time-dependent changes in vancomycin concentrations for each carrier and differences between carriers were analysed. Mean initial antibiotic levels were highest for carrier A (37.5 mg/mL) and lowest for carrier B (5.4 mg/mL). We observed time-dependent, strongly negative linear elution kinetics for carriers A (-0.835; p < 0.001), C (-0.793; p < 0.001), and D (-0.853; p < 0.001). Vancomycin concentrations increased from 48 h to 7 d and dropped thereafter in carriers C and D whilst constantly decreasing at any time point for carrier A. Carrier B showed a shallower decrease. Mean antibiotics levels at 42 d were 1.5 mg/mL, 2.6 mg/mL, 0.1 mg/mL, and 0.1 mg/mL for carriers A, B, C, and D. Differences in mean initial and final vancomycin concentrations for carrier A were significantly larger in comparison to C (p = 0.040). A carrier consisting of allogenic bone chips showed the highest vancomycin-to-carrier ratio and the largest elution over the study period. Whilst vancomycin concentrations were still measurable at 42 days for all carriers, carrier A provided a higher drug-to-carrier ratio and a more consistent antibiotic-releasing profile.

The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints.

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes.

Occupational Health Aspects with Special Focus on Physiological Differences between Office and Metalworkers.

Physical workload adversely impacts inflammation, oxidative stress and mood in heavy workers. We compared these risk parameters between metalworkers (n = 20) and office workers (n = 30), including gender differences. Blood samples were analyzed with thirty parameters to overview endocrinology, inflammation, and psychological and oxidative stress. Despite an adequate antioxidative supply, oxidative stress occurred in metalworkers, as indicated by significantly increased peroxide and homocysteine (Hcy) levels. Moreover, increased concentrations were observed in this group regarding psychological stress and diet-related parameters. Sex-specific differences were determined for physical dimensions, dehydroepiandrosterone sulfate (DHEAS), Hcy, uric acid, triglycerides, osmolality, anti-Mullerian hormone (AMH) and testosterone. Age-associated differences were observed for DHEAS, glycosylated hemoglobin, adrenaline, AMH and testosterone. In male office workers, the body mass index was associated with increased LDL-HDL, cholesterol-HDL and homeostatic model assessment of insulin resistance (HOMA-IR). In conclusion, these results indicate increased oxidative stress and psychological stress in heavy workers independently of adequate antioxidant sustenance. The sedentary occupation of office workers, in turn, favored diseases of affluence. This might be particularly relevant for long-term occupied persons and older workers due to a hormonal shift coming along, given the risk for oxidative stress-related diseases such as cardiovascular disease, particularly in the case of males, based on their lifestyle habits.

The Impact of a High-Carbohydrate/Low Fat vs. Low-Carbohydrate Diet on Performance and Body Composition in Physically Active Adults: A Cross-Over Controlled Trial.

Background: Recently, high-carbohydrate or low-carbohydrate (HC/LC) diets have gained substantial popularity, speculated to improve physical performance in athletes; however, the effects of short-term changes of the aforementioned nutritional interventions remain largely unclear. Methods: The present study investigated the impact of a three-week period of HC/low-fat (HC) diet followed by a three-week wash-out-phase and subsequent LC diet on the parameters of physical capacity assessed via cardiopulmonary exercise testing, body composition via bioimpedance analysis and blood profiles, which were assessed after each of the respective diet periods. Twenty-four physically active adults (14 females, age 25.8 ± 3.7 years, body mass index 22.1 ± 2.2 kg/m2), of which six participants served as a control group, were enrolled in the study. Results: After three weeks of each diet, VO2peak was comparable following both interventions (46.8 ± 6.7 (HC) vs. 47.2 ± 6.7 mL/kg/min (LC; p = 0.58)) while a significantly higher peak performance (251 ± 43 W (HC) vs. 240 ± 45 W (LC); (p = 0.0001), longer time to exhaustion (14.5 ± 2.4 min (HC) vs. 14.1 ± 2.4 min (LC); p = 0.002) and greater Watt/kg performance (4.1 ± 0.5 W/kg (HC) vs. 3.9 ± 0.5 W/kg (LC); p = 0.003) was demonstrated after the HC diet. In both trial arms, a significant reduction in body mass (65.2 ± 11.2 to 63.8 ± 11.8 kg (HC) vs. 64.8 ± 11.6 to 63.5 ± 11.3 kg (LC); both p < 0.0001) and fat mass (22.7% to 21.2%; (HC) vs. 22.3% to 20.6% (LC); both p < 0.0001) but not in lean body mass or skeletal muscle mass was shown when compared to baseline. Resting metabolic rate was not different within both groups (p > 0.05). Total cholesterol and LDL-cholesterol significantly decreased after the HC diet (97.9 ± 33.6 mg/dL at baseline to 78.2 ± 23.5 mg/dL; p = 0.02) while triglycerides significantly increased (76 ± 38 mg/dL at baseline to 104 ± 44 mg/dL; p = 0.005). Conclusion: A short-term HC and LC diet showed improvements in various performance parameters in favor of the HC diet. Some parameters of body composition significantly changed during both diets. The HC diet led to a significant reduction in total and LDL-cholesterol while triglycerides significantly increased.

Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer.

Background/Purpose: This study aims to quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. Materials and methods: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. Results: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n = 12, during treatment n = 19). The pre-treatment LVEF strongly predicted for cardiotoxicity (subdistribution hazard ratio per 5% increase in pre-treatment LVEF = 0.68, 95%CI: 0.48-0.95, p = 0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (hazard ratio per 5% LVEF increase at any time of follow-up = 0.36, 95% CI: 0.2-0.65, p = 0.005). Thirty-four patients (18%) developed an LVEF decline ≥ 5% from pre-treatment to first follow-up ("early LVEF decline"). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF ≥ 60% (n = 117), 15.9% in those with early LVEF decline or pre-treatment LVEF < 60% (n = 65), and 66.7% in those with early LVEF decline and pre-treatment LVEF < 60% (n = 3), (Gray's test p < 0.0001). Conclusion: Cardiotoxicity risk is low in two thirds of women with HER2+ early breast cancer who have pre-treatment LVEF ≥ 60% and no early LVEF decline > 5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting.

Longitudinal Comparison of Automated SARS-CoV-2 Serology Assays in Assessing Virus Neutralization Capacity in COVID-19 Convalescent Sera.

CONTEXT.­: Serologic tests on automated immunology analyzers are increasingly used to monitor acquired immunity against SARS-CoV-2. The heterogeneity of assays raises concerns about their diagnostic performance and comparability. OBJECTIVE.­: To test sera from formerly infected individuals for SARS-CoV-2 antibodies by using 6 automated serology assays and a pseudoneutralization test (PNT). DESIGN.­: Six SARS-CoV-2 serology assays were used to assess 954 samples collected during a 12-month period from 315 COVID-19 convalescents. The tests determined either antibodies against the viral nucleocapsid (anti-NC) or spike protein (anti-S). Two assays did not distinguish between antibody classes, whereas the others selectively measured immunoglobulin G (IgG) antibodies. PNT was used to detect the presence of neutralizing antibodies. RESULTS.­: Comparison of qualitative results showed only slight to moderate concordance between the assays (Cohen κ < 0.57). Significant correlations (P < .001) were observed between the antibody titers from all quantitative assays. However, titer changes were not detected equally. A total anti-S assay measured an increase in 128 of 172 cases (74%) of a suitable subset, whereas all IgG anti-S tests reported decreases in at least 118 (69%). Regarding the PNT results, diagnostic sensitivities of 89% or greater were achieved with positive predictive values of at least 93%. In contrast, specificity changed substantially over time, varying from 20% to 100%. CONCLUSIONS.­: Comparability of serologic SARS-CoV-2 antibody tests is rather poor. Owing to different diagnostic specificities, the tested assays were not equally capable of capturing changes in antibody titers. However, with thoroughly validated cutoffs, IgG-selective anti-S assays are a reliable surrogate test for SARS-CoV-2 neutralizing antibodies in former COVID-19 patients.

Improved overall survival of metastatic renal cell carcinoma patients in the era of modern tyrosine kinase inhibitors and immune checkpoint inhibitors: results from a real-life, population-based Austrian study comprising three decades of follow-up.

Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has substantially advanced over the last three decades, whereby data from controlled clinical trials indicate significant improvements regarding patients' overall survival (OS) in highly selected patient cohorts. The aim of this study is to evaluate the impact of potentially game changing drugs on patients' outcomes by comparing three different historical mRCC treatment eras. Methods: In all, 914 mRCC patients who were diagnosed between July 1985 and September 2020 were included into this observational study and assigned to three different treatment eras ['cytokine', 'first-generation tyrosine kinase inhibitors (TKIs)', and 'modern TKIs/immunotherapy'] based on the EMA approval dates of sunitinib (July 2006) and nivolumab (June 2015) in mRCC treatment. OS was considered the primary study endpoint. Kaplan-Meier analyses, log-rank tests, and uni- and multivariable Cox regression models were performed. Results: OS was significantly longer in patients of the modern TKIs/immunotherapy era (median OS not reached) as compared to the cytokine (2.4 years) and first-generation TKIs era (1.7 years, all p < 0.001). Moreover, patients of the modern TKIs/immunotherapy era demonstrated a significantly better prognosis [hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.32-0.55, p < 0.001] compared to those of the cytokine era, while no statistically significant difference was observed between the cytokine and the first-generation TKIs era cohort (HR: 1.12, 95% CI: 0.89-1.41, p = 0.341). Subgroup analyses stratified by the International Metastatic RCC Database Consortium (IMDC) risk groups showed a significantly longer OS in the modern TKIs/immunotherapy era as compared to first-generation TKIs and cytokines across all IMDC risk groups. Conclusion: Significant advances in the systemic medical treatment of mRCC during the recent decade and the introduction of immunotherapy exerted a major impact on patient outcomes in terms of OS in a real-life population.

Deficiency of B vitamins leads to cholesterol-independent atherogenic transformation of the aorta.

Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors, including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in vivo models of atherosclerosis that resemble the human situation. Here, we have developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development, even at low balloon pressure. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.

Soluble urokinase plasminogen activator receptor (suPAR) predicts critical illness and kidney failure in patients admitted to the intensive care unit.

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3-14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan-Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20-2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7.

Impact of a Single 36 Hours Prolonged Fasting Period in Adults With Type 1 Diabetes - A Cross-Over Controlled Trial.

Prolonged fasting has shown beneficial effects in healthy individuals and in people with chronic diseases. In type 1 diabetes, the effect or even the feasibility of fasting is unclear. We aimed to assess the impact and safety of prolonged fasting in adults with type 1 diabetes. Glycemia was assessed during overnight fasting (12 hours) vs. prolonged fasting (36 hours) via an intermittently-scanned continuous glucose monitoring system. Anthropometric data, metabolic and hormonal markers were compared between both trial arms. After each fasting period, a 75 g oral glucose tolerance test was performed and plasma glucose levels and hormones were assessed. Data were compared via paired t-tests and mixed-model regressions (p ≤ 0.05). Twenty individuals with type 1 diabetes (7 females) with a mean ± SD age of 35 ± 11 years, body mass index (BMI) 24.8 ± 2.8 kg/m2 and HbA1c 54 ± 7 mmol/mol were included. Hypoglycemia/hour (70 mg/dL; <3.9 mmol/L) was similar in both trial arms (12 hrs: 0.07 ± 0.06 vs. 36 hrs: 0.05 ± 0.03, p=0.21). Glycemic excursions during the oral glucose tolerance test were not different after the two fasting periods. Beta-hydroxybutyrate levels were higher after prolonged fasting (p=0.0006). Our study showed that people with type 1 diabetes can safely perform a 36 hours fasting period with a low risk of hypoglycemia and ketoacidosis. Clinical Trial Registration: DRKS.de, identifier DRKS00016148.