Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.

The hepatic acute-phase response is characterized by a massive upregulation of serum proteins, such as haptoglobin and serum amyloid A, at the expense of liver homeostatic functions. Although the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has a well-established role in safeguarding liver function and its cistrome spans around 50% of liver-specific genes, its role in the acute-phase response has received little attention so far. We demonstrate that HNF4A binds to and represses acute-phase genes under basal conditions. The reprogramming of hepatic transcription during inflammation necessitates loss of HNF4A function to allow expression of acute-phase genes while liver homeostatic genes are repressed. In a pre-clinical liver organoid model overexpression of HNF4A maintained liver functionality in spite of inflammation-induced cell damage. Conversely, HNF4A overexpression potently impaired the acute-phase response by retaining chromatin at regulatory regions of acute-phase genes inaccessible to transcription. Taken together, our data extend the understanding of dual HNF4A action as transcriptional activator and repressor, establishing HNF4A as gatekeeper for the hepatic acute-phase response.

Validation of Nutritional Approaches to Modulate Cardiovascular and Diabetic Risk Factors in Patients with Hypertriglyceridemia or Prediabetes-The MoKaRi II Randomized Controlled Study.

Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of both clinical pictures. For the 10-week randomized, controlled, intervention study, 67 subjects with elevated plasma triglyceride (TG) concentrations (≥1.7 mmol/L) and 69 subjects with elevated fasting glucose concentrations (≥5.6 < 7.0 mmol/L) were recruited. The intervention groups received specially developed, individualized menu plans and regular counseling sessions to lower (A) TG or (B) fasting glucose and glycated hemoglobin A1c as well as other cardiovascular and diabetic risk factors. The hypertriglyceridemia intervention group was further supplemented with fish oil (3.5 g/d eicosapentaenoic acid + docosahexaenoic acid). The two control groups maintained a typical Western diet. Blood samples were taken every 2 weeks, and anthropometric data were collected. A follow-up examination was conducted after another 10 weeks. In both intervention groups, there were comparable significant reductions in blood lipids, glucose metabolism, and anthropometric parameters. These results were, with a few exceptions, significantly more pronounced in the intervention groups than in the corresponding control groups (comparison of percentage change from baseline). In particular, body weight was reduced by 7.4% (6.4 kg) and 7.5% (5.9 kg), low-density lipoprotein cholesterol concentrations by 19.8% (0.8 mmol/L) and 13.0% (0.5 mmol/L), TG concentrations by 18.2% (0.3 mmol/L) and 13.0% (0.2 mmol/L), and homeostatic model assessment for insulin resistance by 31.8% (1.1) and 26.4% (0.9) (p < 0.05) in the hypertriglyceridemia and prediabetes intervention groups, respectively. Some of these changes were maintained until follow-up. In patients with elevated TG or fasting glucose, implementing individualized menu plans in combination with regular counseling sessions over 10 weeks led to a significant improvement in cardiovascular and diabetic risk factors.

Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Metabolic Profiling Identifies 1-MetHis and 3-IPA as Potential Diagnostic Biomarkers for Patients With Acute and Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Metabolomics has become a valuable tool for identifying potential new biomarkers and metabolic profiles. It has the potential to improve the diagnosis and prognosis of different phenotypes of heart failure. To generate a distinctive metabolic profile, we assessed and compared the metabolic phenotypes of patients with acute decompensated heart failure (ADHF), patients with chronic heart failure (CHF), and healthy controls. METHODS: Plasma metabolites were analyzed by liquid-chromatography mass spectrometry/mass spectrometry and the MxP Quant 500 kit in 15 patients with ADHF, 50 patients with CHF (25 with dilated cardiomyopathy, 25 with ischemic cardiomyopathy), and 13 controls. RESULTS: Of all metabolites identified to be significantly altered, 3-indolepropionic acid and 1-methyl histidine showed the highest concentration differences in ADHF and CHF compared with control. Area under the curve-receiver operating characteristic analysis showed an area under the curve ≥0.8 for 3-indolepropionic acid and 1-methyl histidine, displaying good discrimination capabilities between control and patient cohorts. Additionally, symmetrical dimethylarginine (mean, 1.97±0.61 [SD]; P=0.01) was identified as a suitable biomarker candidate for ADHF and kynurenine (mean, 1.69±0.39 [SD]; P=0.009) for CHF when compared with control, both demonstrating an area under the curve ≥0.85. CONCLUSIONS: Our study provides novel insights into the metabolic differences between ADHF and CHF and healthy controls. We here identify new metabolites for potential diagnostic and prognostic purposes.

Plasma levels of α1-antitrypsin-derived C-terminal peptides in PiMM and PiZZ COPD patients.

Plasma levels of α1-antitrypsin-derived C-terminal peptides might be valid as novel biomarkers to predict and/or characterise exacerbations in PiMM and PiZZ COPD patients, or to reflect the efficiency of augmentation therapy in PiZZ patients https://bit.ly/3rNJeLd.

Evaluation of Influencing Factors on Metabolism of Land-Based n-3 Poly Unsaturated Fatty Acids-The KoALA Study.

This study aimed to investigate the impact of influencing factors (sex, eicosapentaenoic acid (EPA) status at baseline, linoleic acid (LA) intake, milk fat intake) on the conversion of α-linolenic acid (ALA) obtained from linseed oil into its long-chain metabolites. In addition, the effect of ALA on cardiovascular risk markers was investigated. This study used a parallel design approach by randomly assigning the 134 subjects to one of four diets (high in LA (HLA); low in LA (LLA); high in milk fat (MF); control (Western diet)) each enriched with linseed oil (10 en%, 22-27 mL ≙ 13-16 g ALA). Blood samples were taken at baseline and after 4, 8, and 12 weeks of dietary intervention. The study was fully completed by 105 subjects (57.4 ± 12.1 years; 65.7% female). Results showed that ALA (296-465%), C-20:4n3 (54-140%), and EPA (37-73%) concentrations in erythrocytes increased in all groups (p < 0.01). In contrast, docosahexaenoic acid (19-35%, p < 0.01) and n-3 index (10-21%, p < 0.05) dropped in the HLA, LLA, and control groups. An increase in C-22:5n3 was only observed in the MF (36%) and control groups (11%) (p < 0.05). In addition, an increase in LA (7-27%) was found in the HLA, LLA, and control groups, whereas C-20:3n6 (16-22%), arachidonic acid (10-16%), C-22:4n6 (12-30%), and C-22:5n6 (32-47%) decreased (p < 0.01). The conversion into EPA was higher in men than in women (69 vs. 39%, p = 0.043) and in subjects with low EPA status compared to participants with high EPA status (79 vs. 29%, p < 0.001). A high LA status attenuates the conversion rate. In line with the literature, no clear effects on blood lipids and parameters of glucose metabolism were found in relation to ALA supplementation.

Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk.

BACKGROUND: Sepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk. METHODS: To induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within < 24 h) and severe septic shock (norepinephrine dose > 0.4 µg/kg/min) and 48 healthy age- and sex-matched controls were analyzed for circulating bile acids. To screen for immunosuppressive effects of circulating bile acids, the capability to induce TGR5 activation was computed for each individual bile acid profile by a recently published formula. RESULTS: Although experimental endotoxemia as well as septic shock led to significant increases in total bile acids compared to controls, this increase was mild in most cases. By contrast, there was a marked and significant increase in circulating bile acids in septic shock patients with severe liver failure compared to healthy controls (61.8 µmol/L vs. 2.8 µmol/L, p = 0.0016). Circulating bile acids in these patients were capable to induce immunosuppression, as indicated by a significant increase in TGR5 activation by circulating bile acids (20.4% in severe liver failure vs. 2.8% in healthy controls, p = 0.0139). CONCLUSIONS: Circulating bile acids capable of inducing immunosuppression are present in septic shock patients with severe liver failure. Future studies should examine whether modulation of bile acid metabolism can improve the clinical course and outcome of sepsis in these patients.

Impact of Regular Intake of Microalgae on Nutrient Supply and Cardiovascular Risk Factors: Results from the NovAL Intervention Study.

A 14-day randomized controlled study with a parallel design was conducted with 80 healthy participants. Intervention groups I (IG1) and II (IG2) received a defined background diet and consumed a smoothie enriched with either 15 g of Chlorella dry weight (d.w.) or 15 g of Microchloropsis d.w. daily. Control group II (CG2) received a defined background diet without the smoothie. Control group I (CG1) received neither. Blood samples and 24-h urine were collected at the beginning and the end of the study. Serum concentrations of 25-hydroxyvitamin D3, vitamin D3, selenium, iron, ferritin, transferrin saturation, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol and the LDL-cholesterol/HDL cholesterol ratio decreased in IG1 (p < 0.05), while 25-hydroxyvitamin D2 increased (p < 0.05). In IG2, vitamin D3, 25-hydroxyvitamins D2 and D3 decreased (p < 0.05), while concentrations of fatty acids C20:5n3 and C22:5n3 increased. Serum and urine uric acid increased in IG1 and IG2 (p < 0.05). Microchloropsis is a valuable source of n3 fatty acids, as is Chlorella of vitamin D2. Regular consumption of Chlorella may affect the iron and selenium status negatively but may impact blood lipids positively. An elevated uric acid concentration in blood and urine following the regular consumption of microalgae poses potential risks for human health.

Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance.

Insulin resistance (IR) during obesity is linked to adipose tissue macrophage (ATM)-driven inflammation of adipose tissue. Whether anti-inflammatory glucocorticoids (GCs) at physiological levels modulate IR is unclear. Here, we report that deletion of the GC receptor (GR) in myeloid cells, including macrophages in mice, aggravates obesity-related IR by enhancing adipose tissue inflammation due to decreased anti-inflammatory ATM leading to exaggerated adipose tissue lipolysis and severe hepatic steatosis. In contrast, GR deletion in Kupffer cells alone does not alter IR. Co-culture experiments show that the absence of GR in macrophages directly causes reduced phospho-AKT and glucose uptake in adipocytes, suggesting an important function of GR in ATM. GR-deficient macrophages are refractory to alternative ATM-inducing IL-4 signaling, due to reduced STAT6 chromatin loading and diminished anti-inflammatory enhancer activation. We demonstrate that GR has an important function in macrophages during obesity by limiting adipose tissue inflammation and lipolysis to promote insulin sensitivity.

Association between preoperative serum C-reactive protein level and leukocyte count and postoperative pain after otolaryngological surgery.

PURPOSE: To determine whether the preoperative inflammatory serum C-reactive protein (CRP) and leukocyte count (LEUK) are associated with postoperative pain and complaints after otolaryngological surgery. METHODS: Retrospective evaluation of 680 patients (33% female, median age 50 years) receiving otolaryngological surgery between November 2008 and March 2017 in a tertiary university hospital. Postoperative pain on the first postoperative day was assessed using the validated questionnaire of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including a numeric rating scale for assessment of postoperative pain (NRS, 0-10). The influence of preoperative parameters including CRP and LEUK on patients' postoperative pain was estimated. RESULTS: Mean CRP value was 15.6 ± 34.6 mg/l and mean LEUK value 7.8 ± 3.2 Gpt/l. Patients with pharyngeal surgery had the highest CRP values (34.6 ± 52.9 mg/l), highest LEUK values (9.2 ± 4.2 Gpt/l) and the highest pain levels (3.1 ± 2.4 NRS) compared to all other surgical procedures (all p < 0.05). Higher postoperative pain was associated with LEUK values > 11.3 Gpt/l (r = 0.093, p = 0.016) and higher preoperative chronic pain (r = 0.127, p = 0.001). Multivariate analysis confirmed younger age, female gender, duration of surgery, preoperative chronic pain, type of surgery, and higher LEUK values > 11.3 as independent factors for postoperative pain. Perioperative antibiotics had no effect on the postoperative pain. CONCLUSION: Beyond known factors, preoperative LEUK as inflammation marker is an independent predictor for pain on the first postoperative day.

GBA/GBN-position on the feedback of incidental findings in biobank-based research: consensus-based workflow for hospital-based biobanks.

Incidental research findings pose a considerable challenge to hospital-based research biobanks since they are acting as intermediaries between healthcare and research. In a joint action the centralized biobank ibdw (Interdisciplinary Bank of Biomaterials and Data Wuerzburg) together with local authorities drafted a coherent concept to manage incidental research findings in full compliance with relevant ethical and data privacy regulations. The concept was developed and elaborated in close collaboration with the German Biobank Alliance (GBA). Comprehensive documentation of all steps guarantees the traceability of the process. By a mandatory assessment of the findings prior to re-identification of the individual concerned, unnecessary measures can be avoided. The individual's "right not to know" is respected according to the stipulations of the informed consent. As a general principle any communication with the individual occurs exclusively through the hospital and by competent physicians with appropriate knowledge and communication skills. We propose this scheme as a blueprint for reporting workflows for incidental research findings at hospital-based biobanks.

Non-patient-related SARS-CoV-2 exposure from colleagues and household members poses the highest infection risk for hospital employees in a German university hospital: follow-up of the prospective Co-HCW seroprevalence study.

PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection. CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.

Effect of a regular consumption of traditional and roasted oat and barley flakes on blood lipids and glucose metabolism-A randomized crossover trial.

Background: Regular consumption of the soluble dietary fiber ß-glucan is associated with decreased total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and blood glucose. Barley and oat flakes as natural sources of ß-glucan were roasted to improve sensory quality. The aim of this study was to investigate whether roasting of barley and oat flakes changes the physiological impact of the ß-glucan-rich flakes on glucose and lipid metabolism. Method: A five-armed randomized crossover trial design was used. The intervention study was conducted from May 2018 to May 2019 and included 32 healthy subjects with moderately increased LDL cholesterol (≥2.5 mmol/L). During the 3-week intervention periods, 80 g of roasted or traditional barley or oat flakes, or four slices of white toast bread per day were consumed for breakfast. At the start and the end of each intervention, fasting and postprandial blood was taken. The intervention periods were separated by 3-week wash-out periods. Results: During the interventions with the cereal flakes, TC and LDL cholesterol concentrations were significantly reduced compared to baseline values by mean differences of 0.27-0.33 mmol/L and 0.21-0.30 mmol/L, respectively (p < 0.05), while high-density lipoprotein (HDL) cholesterol was only reduced after the intervention with barley flakes (p < 0.05). After the intervention period with toast, TC and HDL cholesterol increased (p < 0.05). The fasting levels of triglycerides, fasting blood glucose and insulin did not change in any group. The effects of traditional and roasted varieties on blood lipids did not differ between the groups. Conclusion: The regular consumption of traditional or roasted barley and oat flakes contributes to the management of cardiovascular diseases by improving TC and LDL cholesterol. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03648112, identifier NCT03648112.

Immunoadsorption to treat patients with severe post-COVID syndrome.

INTRODUCTION: Following SARS-CoV-2-infection up to 21% of patients will develop post-COVID-syndrome. Autoantibodies (AAbs) targeting neuronal-ß-adrenergic and muscarinic receptors may provide crucial contributions to the pathophysiology of this condition. Immunoadsorption (IA) has been identified as an effective means of removing AAbs and has resulted in clinical improvements of other autoantibody-associated diseases. METHODS: We determined AAb-levels (anti-ß1/ß2 and anti-M3/M4 receptor) in 178 patients diagnosed with post-COVID-syndrome and described the clinical courses of two patients with elevated AAb-levels that underwent IA-treatment. RESULTS: AAbs were detected in 57% (101/178) of patients diagnosed with post-COVID-syndrome. Substantial reductions in AAb-levels and clinical remission were achieved in one of two patients who was treated with IA. However, this patient relapsed within 6 weeks with a concomitant increase in AAb-levels. CONCLUSION: Collectively, AAbs may play a pathophysiologic role in post-COVID and their removal provide transient benefits in some patients. However, these findings should be further investigated in randomized-controlled-trials.

Association of the C-terminal 42-peptide fragment of alpha-1 antitrypsin with the severity of ARDS: A pilot study.

BACKGROUND: Acute respiratory distress syndrome is a life-threatening condition with a hospital mortality rate of up to 40%. Biomarkers related to the pathophysiology of ARDS may not only identify patients at risk but may also serve as potential therapeutic targets. This study examined the association between the proteolytic C-terminal 42-peptide fragment of alpha-1 antitrypsin and ARDS severity. METHODS: The 42-peptide fragment and interleukin-6 levels were measured in 21 patients with mild-to-moderate ARDS and 47 patients with moderate-to-severe ARDS on days 1, 3, and 5 after diagnosis/admission to the intensive care unit. To elucidate the association between both biomarkers and the PaO2/FiO2 ratio, the concentrations of both biomarkers were compared between the two groups, and a multivariate regression analysis was performed. RESULTS: The concentrations of both biomarkers were higher in patients with moderate-to-severe ARDS. While the PaO2/FiO2 ratio increased from day 1 to day 3, the concentrations of both biomarkers decreased. Multivariate regression analysis revealed negative associations between the PaO2/FiO2 ratio and both the C-terminal 42-peptide of alpha-1 antitrypsin and interleukin-6 on day 1 (beta: -0.138, p = 0.052; beta: -0.096, p = 0.004) and on day 3 (beta: -0.157, p = 0.045; beta: -0.106, p = 0.043). INTERPRETATION: The C-terminal 42-peptide of alpha-1 antitrypsin is a new biomarker associated with ARDS severity. Its predictive value in identifying patients at risk of developing moderate-to-severe ARDS must be investigated in additional, independent prospective studies.

Corrigendum: Nutrient intake and nutrition status in vegetarians and vegans in comparison to omnivores-the nutritional evaluation (NuEva) study.

[This corrects the article DOI: 10.3389/fnut.2022.819106.].

Soluble mannose receptor CD206 and von Willebrand factor are early biomarkers to identify patients at risk for severe or necrotizing acute pancreatitis.

BACKGROUND: In acute pancreatitis (AP), microcirculatory dysfunction and leukocyte activation contribute to organ damage, inflammation, and mortality. Given the role of macrophage activation, monocyte recruitment, and microthrombus formation in the early pathogenesis of AP, we examined the macrophage activation marker soluble mannose receptor (sCD206) and the endothelial function marker von Willebrand factor (vWF) in patients admitted for AP. METHODS: In an exploratory analysis, serum sCD206 and plasma vWF were prospectively analyzed on day 1 and day 3 in 81 patients with AP admitted to the hospital. In addition, blood samples from 59 patients with early AP admitted to the intensive care unit and symptom onset < 24 h were retrospectively analyzed. Patients were dichotomized as per study protocol into two groups: (i) "non-severe edematous AP" including patients with mild AP without organ failure and patients with transient organ failure that resolves within 48 h and (ii) "severe/necrotizing AP" including patients with severe AP and persistent organ failure > 48 h and/or patients with local complications. RESULTS: In the prospective cohort, 17% developed severe/necrotizing pancreatitis compared with 56% in the ICU cohort. Serum concentrations of sCD206 on admission were higher in patients with severe/necrotizing AP than in patients with non-severe edematous AP (prospective: 1.57 vs. 0.66 mg/l, P = 0.005; ICU: 1.76 vs. 1.25 mg/l, P = 0.006), whereas other inflammatory markers (leukocytes, C-reactive protein, procalcitonin) and disease severity (SOFA, SAPS II, APACHE II) did not show significant differences. Patients with severe/necrotizing AP had a greater increase in sCD206 than patients with non-severe edematous AP at day 3 in the prospective cohort. In contrast to routine coagulation parameters, vWF antigen levels were elevated on admission (prospective cohort: 375 vs. 257%, P = 0.02; ICU cohort: 240 vs. 184%, P = 0.03). When used as continuous variables, sCD206 and VWF antigen remained predictors of severe/necrotizing AP after adjustment for etiology and age in both cohorts. CONCLUSIONS: sCD206 identifies patients at risk of severe AP at earlier timepoints than routine markers of inflammation and coagulation. Prospective studies are needed to investigate whether incorporating early or repeated measurements into the existing scoring system will better identify patients at increased risk for complications of AP.

Nutrient Intake and Nutrition Status in Vegetarians and Vegans in Comparison to Omnivores - the Nutritional Evaluation (NuEva) Study.

Introduction: In recent years, vegetarian and vegan diets became increasingly important as they are associated with beneficial health outcomes. Therefore, the NuEva study compares the impact of flexitarian, vegetarian, or vegan diets with omnivorous nutritional habits on nutrient intake and risk factors for non-communicable diseases. Methods: A dietary protocol was kept over five days and blood and 24h urine samples were collected to examine the impact of dietary habits [omnivores, n = 65 (Median/Interquartile range: 33/17 yrs.), flexitarians, n = 70 (30/17 yrs.), ovo-lacto vegetarians, n = 65 (28/14 yrs.), vegans, n = 58 (25/10 yrs.)] on nutrient intake, nutrient concentrations in plasma, serum or 24h urine, body composition, and blood lipids. Results: The increased exclusion of animal based foods in the diet (omnivores < flexitarians < vegetarians < vegans) is associated with a decreased intake of energy, saturated fat, cholesterol, disaccharides, and total sugar as well an increased intake of dietary fibers, beta carotene, vitamin E and K. The combined index of the B12 status (4cB12 score) in vegetarians (0.02/0.75) was lower compared to omnivores (0.34/0.58; p ≤ 0.05) and flexitarians (0.24/0.52; p ≤ 0.05). In omnivores vitamin A, vitamin E, ferritin, and the urinary excretion of selenium, iodine, and zinc were higher than in vegans (p ≤ 0.05). In contrast, vegans had the highest concentrations of biotin, folate, and vitamin C. Flexitarians, vegetarians, and vegans had a lower body weight, BMI, and body fat percentage in comparison to omnivores (p ≤ 0.05). In omnivores the concentrations on total cholesterol, total cholesterol/HDL cholesterol ratio, LDL cholesterol, LDL cholesterol/HDL cholesterol ratio, apolipoprotein B, and apolipoprotein B/ apolipoprotein A1 ratio were higher than in vegetarians and vegans (p ≤ 0.05). Conclusion: The NuEva study confirms the position of the Academy of Nutrition and Dietetics that adequately planned vegetarian diets are healthy, nutritionally adequate, and may provide health benefits in the prevention and treatment of non-communicable diseases. Nevertheless, critical nutrients were identified for all groups studied. This highlights the need to develop individual nutritional concepts to ensure an adequate nutrient intake.

Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker.

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.

Development of a new antigen-based microarray platform for screening and detection of human IgG antibodies against SARS-CoV-2.

Strategies to contain the current SARS-CoV-2 pandemic rely, beside vaccinations, also on molecular and serological testing. For any kind of assay development, screening for the optimal antigen is essential. Here we describe the verification of a new protein microarray with different commercially available preparations significant antigens of SARS-CoV-2 that can be used for the evaluation of the performance of these antigens in serological assays and for antibody screening in serum samples. Antigens of other pathogens that are addressed by widely used vaccinations were also included. To evaluate the accuracy of 21 different antigens or antigen preparations on the microarray, receiver operating characteristics (ROC) curve analysis using ELISA results as reference were performed. Except for a single concentration, a diagnostic sensitivity of 1 was determined for all antigen preparations. A diagnostic specificity, as well as an area under the curve (AUC) of 1 was obtained for 16 of 21 antigen preparations. For the remaining five, the diagnostic specificity ranged from 0.942 to 0.981 and AUC from 0.974 to 0.999. The optimized assay was subsequently also applied to determine the immune status of previously tested individuals and/or to detect the immunization status after COVID-19 vaccination. Microarray evaluation of the antibody profiles of COVID-19 convalescent and post vaccination sera showed that the IgG response differed between these groups, and that the choice of the test antigen is crucial for the assay performance. Furthermore, the results showed that the immune response is highly individualized, depended on several factors (e.g., age or sex), and was not directly related to the severity of disease. The new protein microarray provides an ideal method for the parallel screening of many different antigens of vaccine-preventable diseases in a single sample and for reliable and meaningful diagnostic tests, as well as for the development of safe and specific vaccines.