High-sensitive troponin T, suPAR and Beta-2-microglobulin changes in concentration during hemodialysis.

Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by -9.9% after dialysis (95% CI: -13.6% to -6.2%). The average (paired) difference were - 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by -58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by -9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers.

Validation of suPAR turbidimetric assay on Cobas® (c502 and c702) and comparison to suPAR ELISA.

suPAR is a plasma marker of chronic inflammation, and an elevated suPAR is consistently associated with worse outcome in a variety of clinical conditions. Quantification of suPAR is useful for determining patient risk in triage, but there is no fast automatized method for quick determination of suPAR. We developed and validated a rapid latex particle-enhanced turbidimetric immunoassay for quantification of plasma suPAR on the c502 and the c702 Roche Cobas® 8000 measurment systems. The turbidimetric assay was validated against the suPARnostic® ELISA (ViroGates, Denmark). This validation demonstrates suPAR can be analysed by turbidimetry giving very similar results (<15% difference) compared to the ELISA method and the observed correlations (n = 103) were strong, r > 0.95. Roche Cobas® 8000 instruments demonstrated repeatability and repoducibility, CV % at 3.4-4.1 and 5.7-11.4, respectively. The estimated limit of detection was 1.30 µg/L and 1.31 µg/L for the Cobas® c502 and c702, respectively. Dilution tests showed linearity of suPAR from 1.8 to 26.5 µg/L. The acceptable concentrations of Bilirubin, Intralipid and Hemoglobin, were 350 µmol/L, 3.3 g/L and 1.4 g/L, respectively. suPAR can be quantified reproducibly within 10 min using a turbidimetry assay. This assay is faster than ELISA with similar results, making it suitable for clinical routine analysis.

Diagnostic Performance of Plasma SP-D, KL-6, and CC16 in Acutely Hospitalised Patients Suspected of Having Community-Acquired Pneumonia-A Diagnostic Accuracy Study.

Community-acquired pneumonia is a common cause of acute hospitalisation. Identifying patients with community-acquired pneumonia among patients suspected of having the disease can be a challenge, which causes unnecessary antibiotic treatment. We investigated whether the circulatory pulmonary injury markers surfactant protein D (SP-D), Krebs von den Lungen-6 (KL-6), and Club cell protein 16 (CC16) could help identify patients with community-acquired pneumonia upon acute admission. In this multi-centre diagnostic accuracy study, SP-D, KL-6, and CC16 were quantified in plasma samples from acutely hospitalised patients with provisional diagnoses of community-acquired pneumonia. The area under the receiver operator characteristics curve (AUC) was calculated for each marker against the following outcomes: patients' final diagnoses regarding community-acquired pneumonia assigned by an expert panel, and pneumonic findings on chest CTs. Plasma samples from 339 patients were analysed. The prevalence of community-acquired pneumonia was 63%. AUCs for each marker against both final diagnoses and chest CT diagnoses ranged between 0.50 and 0.56. Thus, SP-D, KL-6, and CC16 demonstrated poor diagnostic performance for community-acquired pneumonia in acutely hospitalised patients. Our findings indicate that the markers cannot readily assist physicians in confirming or ruling out community-acquired pneumonia.

Gram Stain and Culture of Sputum Samples Detect Only Few Pathogens in Community-Acquired Lower Respiratory Tract Infections: Secondary Analysis of a Randomized Controlled Trial.

Identification of the bacterial etiology of lower respiratory tract infections (LRTI) is crucial to ensure a narrow-spectrum, targeted antibiotic treatment. However, Gram stain and culture results are often difficult to interpret as they depend strongly on sputum sample quality. We aimed to investigate the diagnostic yield of Gram stain and culture from respiratory samples collected by tracheal suction and expiratory technique from adults admitted with suspected community-acquired LRTI (CA-LRTI). In this secondary analysis of a randomized controlled trial, 177 (62%) samples were collected by tracheal suction, and 108 (38%) by expiratory technique. We detected few pathogenic microorganisms, and regardless of sputum quality, there were no significant differences between the sample types. Common pathogens of CA-LRTI were identified by culture in 19 (7%) samples, with a significant difference between patients with or without prior antibiotic treatment (p = 0.007). The clinical value of sputum Gram stain and culture in CA-LRTI is therefore questionable, especially in patients treated with antibiotics.

Expiratory Technique versus Tracheal Suction to Obtain Good-Quality Sputum from Patients with Suspected Lower Respiratory Tract Infection: A Randomized Controlled Trial.

Microbiological diagnostics of good-quality sputum samples are fundamental for infection control and targeted treatment of lower respiratory tract infections (LRTI). This study aims to compare the expiratory technique and tracheal suction on the quality of sputa from adults acutely hospitalized with suspected LRTI. We performed an open-label, randomized controlled trial. Patients were randomized to sputum sampling by tracheal suction (standard care) or the expiratory technique. The primary outcome was quality of sputum evaluated by microscopy and was analysed in the intention-to-treat population. The secondary outcomes were adverse events and patients experience. In total, 280 patients were assigned to tracheal suction (n = 141, 50.4%) or the expiratory technique (n = 139, 49.6%). Sputum samples were collected from 122 (86.5%) patients with tracheal suction and 67 (48.2%) patients with expiratory technique. Good-quality sputa were obtained more often with tracheal suction than with expiratory technique (odds ratio 1.83 [95% CI 1.05 to 3.19]; p = 0.035). There was no statistical difference in adverse events (IRR 1.21 [95% CI, 0.94 to 1.66]; p = 0.136), but patient experience was better in the expiratory technique group (p < 0.0001). In conclusion, tracheal suction should be considered a routine procedure in emergency departments for patients with suspected LRTI.