Bioactive adrenomedullin and interleukin-6 in COVID-19: potential biomarkers of acute kidney injury and critical illness.

BACKGROUND: The aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients. METHODS: 153 patients with COVID-19 admitted to the emergency department (ED) were included. Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as DPP3 and routinely measured markers were evaluated regarding the endpoints AKI (22/128 hospitalized patients) and a composite endpoint of admission to intensive care unit and/or in-hospital death (n = 26/153 patients). RESULTS: Bio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p < 0.001). According to ROC analyses IL-6 and bio-ADM had the largest AUC (0.84 and 0.81) regarding the detection of AKI. Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint (each p < 0.001). Regarding the composite endpoint ROC analysis showed an AUC of 0.89 for IL-6 and 0.83 for bio-ADM in COVID-19 patients. In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and the composite endpoint in COVID-19 patients (as well as creatinine regarding the composite endpoint; each p < 0.05), opposite to leukocytes, C-reactive protein (CRP) and dipeptidyl peptidase 3 (DPP3; each p = n.s.). CONCLUSION: Elevated levels of bio-ADM and IL-6 are associated with AKI and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED.

Restoration of von Willebrand factor after transcatheter aortic valve replacement-A possible cause for posttranscatheter aortic valve replacement thrombocytopenia?

OBJECTIVES: The aim of the current study was to analyze the clinical and procedural predictors of thrombocytopenia and the relationship between the decrease in platelet count (DPC) and change in vWF function (ΔvWF) after transcatheter aortic valve replacement (TAVR). BACKGROUND: TAVR often causes temporary thrombocytopenia. At the same time, TAVR leads to a restoration of von Willebrand factor (vWF) function. METHODS: One hundred and forty-one patients with severe aortic stenosis undergoing TAVR were included in the study. Platelet count and vWF function (vWF:Ac/Ag ratio) were assessed at baseline and 6 h after TAVR. Thrombocytopenia was defined as platelet count <150/nL. RESULTS: Median platelet count at baseline was 214/nL (interquartile range [IQR]: 176-261) and decreased significantly to 184/nL (IQR: 145-222) 6 h after TAVR. The number of patients with thrombocytopenia increased from 12.8% at baseline to 29.1% after 6 h. DPC 6 h after TAVR showed a significant correlation with ΔvWF (r = - 0.254, p = 0.002). Patients with DPC > 20% had significantly higher ΔvWF (10.9% vs. 6.5%, p = 0.021). Obese patients showed a significantly lower DPC (11.8% vs. 19.9%, p = 0.001). In multivariate analysis, ΔvWF 6 h after TAVR was the only significant predictor for DPC > 20% (p = 0.017). CONCLUSIONS: The restoration of vWF after TAVR is a significant predictor for DPC after TAVR. An increased platelet consumption due to vWF restoration could play a key role in the development of thrombocytopenia after TAVR.

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates.

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34-24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30-17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients.

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.5 ± 7.8 kg/m², aged 45 ± 12 years), participating in a standardized weight reduction program, and in 74 lean controls (mean BMI 24.6 ± 3.3 kg/m², aged 41.7 ± 13.4 years). Allele numbers of all 93 SNPs were added to a GRS. Anthropometric parameters, parameters of glucose/insulin and lipid metabolism were assessed standardized after a 12 hours fast. GRS was significantly different between controls and obese individuals (unweighted GRS: 86.6 vs 89.0, P = .002; weighted GRS: 84.9 vs 88.3, P = .005). Furthermore, linear regression analysis showed significant associations of GRS with BMI ( P < .0001), weight ( P = .0005), waist circumference ( P = .0039), fat mass ( P < .0001) and epicardial fat thickness ( P = .0032), yet with small effect sizes ( r ² < 0.06). In conclusion, in our study GRS could differentiate between extreme obese and lean individuals, and was associated with BMI and its related traits, yet with small effect sizes.

Measuring and monitoring light pollution: Current approaches and challenges.

Understanding the causes and potential mitigations of light pollution requires measuring and monitoring artificial light at night (ALAN). We review how ALAN is measured, both from the ground and through remote sensing by satellites in Earth orbit. A variety of techniques are described, including single-channel photometers, all-sky cameras, and drones. Spectroscopic differences between light sources can be used to determine which are most responsible for light pollution, but they complicate the interpretation of photometric data. The variability of Earth's atmosphere leads to difficulty in comparisons between datasets. Theoretical models provide complementary information to calibrate experiments and interpret their results. Here, we identify several shortcomings and challenges in current approaches to measuring light pollution and suggest ways forward.

Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19.

INTRODUCTION: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. METHODS: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. RESULTS: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28-11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13-6.28] per SD). CONCLUSION: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19.

Aerosol impact on light pollution in cities and their environment.

Measurements of artificial light at night represent an incredible challenge as the optical state of the atmosphere is highly unstable thus making both long-term trend analyses and inter-comparison of multiple observations difficult. Variations of atmospheric parameters, caused by either natural or anthropogenic processes, can massively influence the level of resulting night sky brightness caused by light pollution. Focusing on six parameters, either from aerosol optics or emission properties of light sources, this work literarily and numerically examines defined variations in aerosol optical depth, asymmetry parameter, single scattering albedo, ground surface reflectance, direct uplight ratio, and aerosol scale height. For each individual element the effect size and angular reliance is investigated, with results indicating that besides the aerosol scale height all play non-negligible roles in forming skyglow and environmental impact. Especially variations in aerosol optical depth and city emission function displayed severe discrepancies in consequential light pollution level. Hence, future improvement on atmospheric condition, i.e., air quality, focusing particularly on discussed elements indicates to positively influence the level of environmental impact caused by artificial light at night. We underline the need of inclusion of our outcomes to urban development and civil engineering processes in order to create or protect habitable areas for humans, wildlife and nature.

Negative Pressure Wound Therapy with Instillation: Analysis of the Rinsing Fluid as a Monitoring Tool and Approach to the Inflammatory Process: A Pilot Study.

BACKGROUND: Negative pressure wound therapy with instillation (NPWTi) is an established wound conditioning tool. Previous investigations discovered that the rinsing fluid is a suitable monitoring tool containing various cells and cytokines. METHODS: The aim of this pilot study was to analyze rinsing fluid samples from patients treated with NPWTi and link them to the clinical course, including microbiological contamination. In 31 consecutive patients with acute and chronic wounds, laboratory analysis was performed to evaluate IL-6, IL-8, bFGF, Tnf-a, and VEGF. RESULTS: IL-6 showed a significant increase to 1540 pg/mL on day two and 860 pg/mL on day four (p = 0.01 and p = 0.04, resp.). IL-8 steadily increased from a median of 2370 pg/mL to a maximum of 19,400 pg/mL on day three (p = 0.01). The median bFGF showed a steady decline from 22 pg/mL to 10 pg/m (p = 0.35) on day three. The median Tnf-a increased from 11 pg/mL to 44 pg/mL (p = 001). The median VEGF values fluctuated but showed an overall increase from 35 pg/mL to 250 pg/mL (p = 0.07). Regarding IL-8, diabetic and non-diabetic patients both showed a gradual increase with non-significant higher median values for the diabetics. The subgroup analysis of IL-6 showed increasing and higher values in cases with bacterial superinfections (p = 0.07). CONCLUSION: We were able to use an established wound conditioning tool to gather important information about the inflammatory response during NPWTi treatment. Cytokine and cell courses were mostly consistent with the literature, especially in diabetic patients, and should be further investigated.

Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions.

Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). In n = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results were assessed for translational relevance using a human-based model: induced pluripotent stem cell derived cardiomyocytes underwent field stimulation for 7 days (TACH-iPSC-CM). TCM animals showed systolic dysfunction compared to SHAM (fractional shortening 37.8 ± 1.0% vs. 21.9 ± 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 ± 14.5 µm2 vs. 538.9 ± 23.8 µm2, p < 0.001) without fibrosis. Mitochondria were shifted to the intercalated discs and enlarged. Mitochondrial membrane potential remained stable in TCM. The metabolite profiles of ELVD and TCM were characterised by profound depletion of tricarboxylic acid cycle intermediates. Redox balance was shifted towards a more oxidised state (ratio of reduced to oxidised nicotinamide adenine dinucleotide 10.5 ± 2.1 vs. 4.0 ± 0.8, p < 0.01). The mitochondrial acetylome remained largely unchanged. Neither TCM nor TACH-iPSC-CM showed relevantly increased levels of reactive oxygen species. Oxidative phosphorylation capacity of TCM decreased modestly in skinned fibres (168.9 ± 11.2 vs. 124.6 ± 11.45 pmol·O2·s-1·mg-1 tissue, p < 0.05), but it did not in isolated mitochondria. The pattern of mitochondrial dysfunctions detected in two models of tachycardiomyopathy diverges from previously published characteristic signs of other heart failure aetiologies.

Higher allostatic load in work-related burnout: The Regensburg Burnout Project.

BACKGROUND: Burnout and chronic work stress have been linked to various negative health outcomes. While the mechanisms underlying this interplay are still unclear, the allostatic load (AL) model was suggested to demonstrate a possible biological pathway. However, previous studies provided divergent results regarding the association between burnout and AL, probably also due to the heterogeneity of selected samples. Therefore, the aim of the present study was to examine differences in AL between a conceptually strictly specified group of individuals suffering from burnout (BO group) and a healthy comparison group (HC group). METHODS: After a multi-stage recruitment procedure with strict inclusion criteria based on burnout symptomatology and pathogenesis, the BO group (n = 56) was compared to the HC group (n = 65) regarding an index of AL. The AL-index included 14 parameters: high-sensitivity c-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), fibrinogen, d-dimer, plasminogen activator inhibitor 1 (PAI-1), glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL) cholesterol, total cholesterol to HDL cholesterol ratio (TC/HDL), dehydroepiandrosterone-sulphate (DHEA-S), systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), and body fat percentage. RESULTS: The BO group showed significantly higher AL-scores in comparison to the HC group. This effect remained significant after adjusting for sex, age, and smoking status. Additionally, burnout symptoms (assessed with the Maslach Burnout Inventory; MBI), MBI-subscales emotional exhaustion and depersonalization as well as chronic work stress (assessed with the effort-reward imbalance questionnaire) were significantly associated with higher AL-scores. CONCLUSIONS: Consistent with our hypothesis, we detected higher AL-scores in the BO compared to the HC group, indicating a greater cumulative physiological burden in individuals suffering from burnout. Given the high heterogeneity in individuals experiencing burnout symptoms, future studies may focus on well-specified subgroups, when examining the association between burnout and psychophysiological dysregulations.

The impact of bicuspid aortic valve morphology on von Willebrand factor function in patients with severe aortic stenosis and its change after TAVI.

BACKGROUND: Aortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI). METHODS: 143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (Pmean), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA). RESULTS: AVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67-0.86) vs. 0.83 (IQR 0.74-0.93), p < 0.05] and in patients with BAV compared to TAV [0.70 (IQR 0.63-0.78) vs. 0.81 (IQR 0.71-0.89), p < 0.05]. Normalization of vWF:Ac/Ag ratio was achieved in 61% patients 24 h after TAVI. As in the overall study cohort, vWF:Ac/Ag ratio increased significantly in all severe AS subgroups 6 h after TAVI (each p < 0.05). Regarding binary logistic regression analysis, BAV was the only significant predictor for AVWS. CONCLUSIONS: BAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology.

Triple apheresis platelet concentrate quality after pneumatic tube system, conveyor box, and courier transport: An observational study.

Background and Aims: Platelets are prone to activation from handling; they are therefore transported as gently as possible, most commonly by courier. Speedier methods like pneumatic tube system (PTS) transport could improve patient care but may subject platelets to mechanical stress. To test the impact of mechanical stress caused by transport, we compared a PTS with a conveyor box and courier transport on apheresis platelet function. Methods: Fourteen apheresis platelet concentrate triple donations were analyzed by light transmission aggregometry (LTA), rotational thrombelastometry (ROTEM), and flow cytometry before and after indoor transport over 800 m by PTS, conveyor, and courier, respectively, while recording shocks and vibrations with a high-frequency acceleration data logger. Shock index scores were calculated as shock intensity (g-force) times frequency. Results: The shock index was 81 for courier, 6279 for conveyor, and 9075 for PTS. Flow cytometry revealed no significant difference in platelet surface expression of CD62p before (16%) and after transport via courier (15%), conveyor (14%), or PTS (16%). LTA with adenosine phosphate and thrombin receptor-activating peptide-6 resulted in comparable platelet aggregation for courier, conveyor, and PTS. ROTEM assays showed no relevant differences in coagulation time, clot formation time, and maximum clot firmness between transport modes. Conclusion: Though the mechanical challenge was smallest with courier transport, there were no significant differences in platelet activation or aggregation between the three transport modes. These data contradict restrictions on the use of PTSs for platelet concentrate transport.

Phosphatidylserine Synthase PTDSS1 Shapes the Tumor Lipidome to Maintain Tumor-Promoting Inflammation.

An altered lipidome in tumors may affect not only tumor cells themselves but also their microenvironment. In this study, a lipidomics screen reveals increased amounts of phosphatidylserine (PS), particularly ether-PS (ePS), in murine mammary tumors compared with normal tissue. PS was produced by phosphatidylserine synthase 1 (PTDSS1), and depletion of Ptdss1 from tumor cells in mice reduced ePS levels accompanied by stunted tumor growth and decreased tumor-associated macrophage (TAM) abundance. Ptdss1-deficient tumor cells exposed less PS during apoptosis, which was recognized by the PS receptor MERTK. Mammary tumors in macrophage-specific Mertk-/- mice showed similarly suppressed growth and reduced TAM infiltration. Transcriptomic profiles of TAMs from Ptdss1-knockdown tumors and Mertk-/- TAMs revealed that macrophage proliferation was reduced when the Ptdss1/Mertk pathway was targeted. Moreover, PTDSS1 expression correlated positively with TAM abundance but negatively with breast carcinoma patient survival. PTDSS1 thus may be a target to modify tumor-promoting inflammation. SIGNIFICANCE: This study shows that inhibiting the production of ether-phosphatidylserine by targeting phosphatidylserine synthase PTDSS1 limits tumor-associated macrophage expansion and breast tumor growth.

NAG: potential cardiorenal biomarker indicates the progression of chronic kidney disease in implantable cardioverter defibrillator patients, contrary to KIM-1.

Aim: NAG and KIM-1 as markers of tubular damage are suggested as potential biomarkers for the cardiorenal syndrome. The aim of the study was to assess the prognostic capability of NAG and KIM-1 regarding progression of chronic kidney disease (CKD) in patients with implantable cardioverter defibrillator (ICD). Materials & methods: We included 313 patients with an ICD and collected plasma and urine samples. Follow-up was performed after 51 months (interquartile range [IQR]: 25-55). The outcome of interest was continuous CKD progression defined as persistent decline in estimated glomerular filtration rate category accompanied by a ≥25% drop of baseline estimated glomerular filtration rate. Results: An average of four (IQR: 2-6) follow-up values of serum creatinine per patient were obtained. During follow-up 29 patients (9%) developed a continuous CKD progression. NAG was shown as independent predictor for continuous CKD progression (p = 0.01), opposite to KIM-1 (p = n.s.). Conclusion: NAG was shown as predictor for a progressive and real deterioration of kidney function in patients with ICD.

Evaluation of a multimarker panel in chronic heart failure: a 10-year follow-up.

Aim: We assessed the 10-year prognostic role of 11 biomarkers with different pathophysiological backgrounds. Materials & methods/results: Blood samples from 144 patients with heart failure were analyzed. After 10 years of follow-up (median follow-up was 104 months), data regarding all-cause mortality were acquired. Regarding Kaplan-Meier analysis, all markers, except TIMP-1 and GDF-15, were significant predictors for all-cause mortality. We created a multimarker model with nt-proBNP, hs-TnT and IGF-BP7 and found that patients in whom all three markers were elevated had a significantly worse long-time prognosis than patients without elevated markers. Conclusion: In a 10-year follow-up, a combination of three biomarkers (NT-proBNP, hs-TnT, IGF-BP7) identified patients with a high risk of mortality.

Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study.

OBJECTIVE: European guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age. DESIGN: A cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg). SETTING: Study population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany. PARTICIPANTS: A random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction. RESULTS: Among the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70-74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90-95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70-74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90-95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea <60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%. CONCLUSION: In the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

Kidney injury molecule-1: potential biomarker of acute kidney injury and disease severity in patients with COVID-19.

AIMS: The aim of the current study was to evaluate whether tubular markers kidney injury molecule-1 (KIM-1) and N-acetyl-ß-glucosaminidase (NAG) are related to acute kidney injury (AKI) and severe disease in patients with COVID-19. METHODS AND RESULTS: In this prospective observational clinical trial we examined a cohort of 80 patients with proof of acute respiratory infection and divided them into a COVID-19 cohort (n = 54) and a control cohort (n = 26). KIM-1 and NAG were measured from urine samples collected in the emergency department. We assessed the development of AKI, admission to the intensive care unit (ICU) and intrahospital death as clinical endpoints. Urinary KIM-1 and NAG were not significantly different between patients with SARS-CoV-2 and those with other respiratory infections (each p = n.s.). Eight patients from the COVID-19 cohort and five of the non-COVID-19-patients suffered from acute kidney injury during their stay. Nine COVID-19 patients and two non-COVID-19 patients were admitted to the ICU. KIM-1 was significantly elevated in COVID-19 patients with, compared to those without AKI (p = 0.005), as opposed to NAG and creatinine (each p = n.s.). Furthermore, KIM-1 was significantly elevated in the patients with COVID-19 that had to be transferred to the ICU (p = 0.015), in contrast to NAG and creatinine (each p = n.s.). CONCLUSION: Assessing KIM-1 in patients with COVID-19 might provide additional value in recognizing AKI at an early stage of disease. Further, KIM-1 might indicate higher risk for clinical deterioration as displayed by admission to the ICU.

Analysis of Rinsing Fluid during Negative Pressure Wound Therapy with Instillation: A Potential Monitoring Tool in Acute and Chronic Wound Treatment. A Pilot Study.

BACKGROUND: During negative pressure wound therapy (NPWT), open wounds are draped with a nontransparent sponge, making daily wound evaluation impossible. Sometimes, late or undetected bacterial infections and postoperative bleeding result in repetitive surgery, thus prolonging inpatient time. With the introduction of additional fluid instillation (NPWTi), the wound surface is rinsed, and bacteria, proteins and biomarkers are flushed into a collecting canister, which is later discarded. METHODS: The aim of this pilot study was to analyze rinsing fluid samples (0.9% sodium chloride) from the NPWTi device in patients with acute and chronic wounds. In 31 consecutive patients a standardized laboratory analysis was performed to evaluate cellular composition and potassium, phosphate, lactate dehydrooxygenase, pH and total protein levels. RESULTS: While there was an increase in the total cellular amount and the number of polymorphonuclear cells, the number of red blood cells (RBC) decreased after surgery. Potassium and pH showed no significant changes in the first three postoperative days, whereas total protein showed an undulant and partially significant course. CONCLUSION: We were able to quantify cellular metabolites by analyzing the rinsing fluid of NPWTi. We propose the analysis of this material as a novel and potentially promising tool to monitor wound status without removal of the dressing. The establishment of reference values might help to improve the NPWTi therapy.

Urinary N-terminal pro-brain natriuretic peptide: prognostic value in patients with acute chest pain.

AIMS: The objective of this study was to investigate the prognostic value of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with plasma NT-proBNP in patients presenting with acute chest pain in the emergency department. METHODS AND RESULTS: We measured simultaneously plasma and urinary NT-proBNP at admission in 301 patients with acute chest pain. In our cohort, 174 patients suffered from acute coronary syndrome (ACS). A follow-up (median of 55 months) was performed regarding the endpoints all-cause mortality and major adverse cardiac events (mortality, congestive heart failure, ACS with the necessity of a coronary intervention, and stroke). Fifty-four patients died during follow-up; 98 suffered from the combined endpoint. A significant and positive correlation of urinary and plasma NT-proBNP was found (r = 0.87, P < 0.05). Patients with troponin positive ACS had significantly elevated levels of plasma and urinary NT-proBNP compared with those with unstable angina pectoris or chest wall syndrome (each P < 0.05). The highest levels of both biomarkers were found in patients with congestive heart failure (each P < 0.05). According to Kaplan-Meier analysis, plasma and urinary NT-proBNP were significant predictors for mortality and the combined endpoint in the whole study cohort and in the subgroup of patients with ACS (each P < 0.05). Regarding Cox regression analysis, plasma and urinary NT-proBNP were independent predictors for mortality and the combined endpoint (each P < 0.05). CONCLUSIONS: Urinary NT-proBNP seems to provide a significant predictive value regarding the endpoints all-cause mortality and major adverse cardiac events in patients with acute chest pain and those with ACS.