| 1. |
- Albert, Christian, et al.
(författare)
-
Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy : A Systematic Review and Meta-analysis
- 2020
-
Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 76:6, s. 826-
-
Forskningsöversikt (refereegranskat)abstract
- Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
|
|
| 2. |
- Björkman, Lena, 1965, et al.
(författare)
-
The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment
- 2016
-
Ingår i: Molecular and Cellular Biology. - : Informa UK Limited. - 0270-7306 .- 1098-5549. ; 36:20, s. 2583-2595
-
Tidskriftsartikel (refereegranskat)abstract
- Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca2+, and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased by tumor necrosis factor alpha (TNF-alpha) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation of desensitized FFA2R was induced by this drug, suggesting that the cytoskeleton is not directly involved in terminating the response. The functional and regulatory differences between the receptors that recognize short-chain fatty acids and formylated peptides, respectively, imply different roles of these receptors in the orchestration of inflammation and confirm the usefulness of a selective FFA2R agonist and antagonist as tools for the exploration of the precise role of the FFA2R.
|
|
| 3. |
- Filevich, Elisa, et al.
(författare)
-
Day2day : Investigating daily variability of magnetic resonance imaging measures over half a year
- 2017
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most studies of brain structure and function, and their relationships to cognitive ability, have relied on inter-individual variability in magnetic resonance (MR) images. Intra-individual variability is often ignored or implicitly assumed to be equivalent to the former. Testing this assumption empirically by collecting enough data on single individuals is cumbersome and costly. We collected a dataset of multiple MR sequences and behavioural covariates to quantify and characterize intra-individual variability in MR images for multiple individuals. Methods and design: Eight participants volunteered to undergo brain scanning 40-50 times over the course of 6 months. Six participants completed the full set of sessions. T1-weighted, T2*-weighted during rest, T2-weighted high-resolution hippocampus, diffusion-tensor imaging (DTI), and proton magnetic resonance spectroscopy sequences were collected, along with a rich set of stable and time-varying physical, behavioural and physiological variables. Participants did not change their lifestyle or participated in any training programs during the period of data collection. Conclusion: This imaging dataset provides a large number of MRI scans in different modalities for six participants. It enables the analysis of the time course and correlates of intra-individual variability in structural, chemical, and functional aspects of the human brain.
|
|
| 4. |
- Jonmarker, Sandra, et al.
(författare)
-
Effects of 12 mg vs. 6 mg dexamethasone on thromboembolism and bleeding in patients with critical COVID-19-a post hoc analysis of the randomized, blinded COVID STEROID 2 trial
- 2023
-
Ingår i: Annals of Intensive Care. - : SPRINGER. - 2110-5820 .- 2110-5820. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19.MethodsUsing additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care.ResultsWe included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of - 0.5% (95% CI - 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes.ConclusionsAmong patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.
|
|
| 5. |
- Lindstrom, Ann-Charlotte, et al.
(författare)
-
Nationwide case-control study of risk factors and outcomes for community-acquired sepsis
- 2021
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Sepsis is the main cause of death in the intensive care units (ICU) and increasing incidences of ICU admissions for sepsis are reported. Identification of patients at risk for sepsis and poor outcome is therefore of outmost importance. We performed a nation-wide case-control study aiming at identifying and quantifying the association between co-morbidity and socio-economic factors with intensive care admission for community-acquired sepsis. We also explored 30-day mortality. All adult patients (n=10,072) with sepsis admitted from an emergency department to an intensive care unit in Sweden between 2008 and 2017 and a control population (n=50,322), matched on age, sex and county were included. In the sepsis group, 69% had a co-morbid condition at ICU admission, compared to 31% in the control group. Multivariable conditional logistic regression analysis was performed and there was a large variation in the influence of different risk factors associated with ICU-admission, renal disease, liver disease, metastatic malignancy, substance abuse, and congestive heart failure showed the strongest associations. Low income and low education level were more common in sepsis patients compared to controls. The adjusted OR for 30-day mortality for sepsis patients was 132 (95% CI 110-159) compared to controls.
|
|
| 6. |
- Martensson, Johan, et al.
(författare)
-
Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction
- 2013
-
Ingår i: Biomarkers. - 1354-750X .- 1366-5804. ; 18:4, s. 349-356
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by injured kidney cells as well as by activated neutrophils in response to bacterial infections. We assessed the influence of acute renal dysfunction on the association between plasma NGAL and sepsis. Methods: NGAL was measured daily in 138 critically ill patients. Simultaneous recordings of sepsis status and fluctuations in renal function were made. Results: Elevated NGAL was associated with sepsis independent of level of acute renal dysfunction. A cut-off value of 98 ng/mL distinguished sepsis from systemic inflammation with high sensitivity (0.77) and specificity (0.79). Conclusions: Plasma NGAL can help clinicians to identify bacterial infections in critically ill patients.
|
|
| 7. |
- Martensson, Johan, et al.
(författare)
-
Immunoassays distinguishing between HNL/NGAL released in urine from kidney epithelial cells and neutrophils
- 2012
-
Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 413:19-20, s. 1661-1667
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The distinction between monomeric human neutrophil lipocalin/neutrophil gelatinase-associated lipocalin (HNL/NGAL), secreted by injured kidney tubular cells, and dimeric HNL/NGAL, released by activated neutrophils, is important to accurately diagnose acute kidney injury (AKI).Methods: 132 urine samples from 44 intensive care unit (ICU) patients and five urine samples from non-ICU patients with urinary tract infections (UTIs) were analyzed by two monoclonal enzyme-linked immunosorbent assays (ELISA-1 and ELISA-2). The presence of monomeric and/or dimeric HNL/NGAL in each sample was visualized by Western blotting.Results: The ELISA-1 detected both monomeric and dimeric HNL/NGAL whereas the ELISA-2 almost exclusively detected dimeric HNL/NGAL with an area under the receiver-operating characteristics curve (AuROC) of 0.90. The ELISA-1/ELISA-2 ratio detected the monomeric form with an AuROC of 0.92. In 32 AKI patients, dimer-specific EUSA-2 levels decreased pre-AKI whereas the monomer-specific ELISA-1/ELISA-2 ratio gradually increased beyond AKI diagnosis. High EUSA-2 levels and/or low ELISA-1/ELISA-2 ratios detected a predominance of dimeric HNL/NGAL in urine from the patients with tills.Conclusions: In combination, our two ELISAs distinguish monomeric HNL/NGAL, produced by the kidney epithelium, from dimeric HNL/NGAL, released by neutrophils during AKI development, as well as reduce the confounding effect of neutrophil involvement when bacteriuria is present.
|
|
| 8. |
- Martensson, Johan, et al.
(författare)
-
Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury
- 2010
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 36:8, s. 1333-1340
-
Tidskriftsartikel (refereegranskat)abstract
- To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock. Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine alpha 1-microglobulin. Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock. pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.
|
|
| 9. |
- Martensson, Nils, et al.
(författare)
-
On the relation between X-ray Photoelectron Spectroscopy and XAFS
- 2013
-
Ingår i: 15th International Conference On X-Ray Absorption Fine Structure (XAFS15). - : IOP Publishing.
-
Konferensbidrag (refereegranskat)abstract
- XAFS and X-ray Photoelectron Spectroscopy (XPS) are element specific techniques used in a great variety of research fields. The near edge regime of XAFS provides information on the unoccupied electronic states of a system. For the detailed interpretation of the XAFS results, input from XPS is crucial. The combination of the two techniques is also the basis for the so called core-hole clock technique. One of the important aspects of photoelectron spectroscopy is its chemical sensitivity and that one can obtain detailed information about the composition of a sample. We have for a series of carbon based model molecules carefully investigated the relationship between core level photoelectron intensities and stoichiometry. We find strong EXAFS-like modulations of the core ionization cross sections as function of photon energy and that the intensities at high photon energies converge towards values that do not correspond to the stoichiometric ratios. The photoelectron intensities are dependent on the local molecular structure around the ionized atoms. These effects are well described by molecular calculations using multiple scattering theory and by considering the effects due to monopole shake-up and shake-off as well as to intramolecular inelastic scattering processes.
|
|
| 10. |
- Martensson, T., et al.
(författare)
-
Clinical relevance of endoscopy with histopathological assessment in children with suspected gastrointestinal graft-versus-host disease
- 2020
-
Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:7
-
Tidskriftsartikel (refereegranskat)abstract
- Endoscopy with histopathological assessment is an established practice to confirm gastrointestinal graft-versus-host disease (GI-GVHD). However, the clinical relevance of this approach in children is incompletely evaluated. In a retrospective cohort study, we investigated the frequency of treatment changes in response to histopathological findings in all children (<18 years) in Sweden who underwent endoscopy for suspected GI-GVHD (2000-2013) after receiving hematopoietic stem cell transplantation. Sixty-eight children with ninety-one endoscopic occasions were enrolled. At the time of endoscopy, anti-GI-GVHD treatment was ongoing in 71% (65/91). In 18% (12/65) with ongoing treatment, no histopathological evidence of GI-GVHD or another cause to justify anti-GI-GVHD treatment was found. In 48% (44/91), endoscopy with histopathological assessment led to changes in the treatment regimen. Re-endoscopy was more frequent among those with treatment changes, versus unchanged treatment, 39% (17/44) and 13% (6/47), respectively (P = .007). Histopathological findings generating treatment changes were as follows: GI-GVHD in 68% (30/44), normal histology in 25% (11/44), and an alternative diagnosis in 7% (3/44). In conclusion, this study supports that endoscopy with histopathological assessment should be considered in all children with suspected GI-GVHD.
|
|
