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- Zaghrini, C., et al.
(författare)
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Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy
- 2019
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538. ; 95:3, s. 666-679
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) are emerging as biomarkers to classify membranous nephropathy (MN) and to predict outcome or response to treatment. Anti-THSD7A autoantibodies are detected by Western blot and indirect immunofluorescence test (IIFT). Here, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) optimized for quantitative detection of anti-THSD7A autoantibodies. Among 1012 biopsy-proven MN patients from 6 cohorts, 28 THSD7A-positive patients were identified by ELISA, indicating a prevalence of 2.8%. By screening additional patients, mostly referred because of PLA2R1-unrelated MN, we identified 21 more cases, establishing a cohort of 49 THSD7A-positive patients. Twenty-eight patients (57%) were male, and male patients were older than female patients (67 versus 49 years). Eight patients had a history of malignancy, but only 3 were diagnosed with malignancy within 2 years of MN diagnosis. We compared the results of ELISA, IIFT, Western blot, and biopsy staining, and found a significant correlation between ELISA and IIFT titers. Anti-THSD7A autoantibodies were predominantly IgG4 in all patients. Eight patients were double positive for THSD7A and PLA2R1. Levels of anti-THSD7A autoantibodies correlated with disease activity and with response to treatment. Patients with high titer at baseline had poor clinical outcome. In a subgroup of patients with serial titers, persistently elevated anti-THSD7A autoantibodies were observed in patients who did not respond to treatment or did not achieve remission. We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.
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- Albert, Christian, et al.
(författare)
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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
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 76:6, s. 826-
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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.
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| 18. |
- Arbyn, M, et al.
(författare)
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Methods for screening and diagnosis
- 2007
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Ingår i: 2nd edition of the EU Guidelines for cervical cancer screening. - 9789279076985 ; , s. 69-141
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Basu, P, et al.
(författare)
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Erratum
- 2018
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 143:1, s. E1-E1
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Tidskriftsartikel (refereegranskat)
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- Bell, M, et al.
(författare)
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Comparison of the Accuracy of the Novel PrisMax Continuous Renal Replacement Therapy System to the Classic Prismaflex System
- 2019
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 47:1-3, s. 166-170
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> We assessed how the novel PrisMax continuous renal replacement therapy (CRRT) system performed in an international multicentre setting. The system has multiple novel tools aiming to increase accuracy and dose delivery. <b><i>Methods:</i></b> Data was prospectively collected from 7 intensive care units in 6 countries. The PrisMax device data logs constituted the raw material and last generation Prismaflex data was used as comparison. Clinical parameters like treatment time, filter life span, downtime as well as prescribed and delivered dose were recorded. <b><i>Results:</i></b> PrisMax delivered/prescribed effluent ratios (mean ± SD) 0.92 ± 0.15 vs. Prismaflex ratios 0.85 ± 0.21, <i>p</i> < 0.001; delivered effluent dose (mL/kg/h) was 18.16 ± 12.93 vs. 10.95 ± 10.96, <i>p</i> < 0.0001; and (Kt/V) 0.76 ± 0.52 vs. 0.44 ± 0.44, <i>p</i> < 0.0001. Moreover, downtime was 27 minutes less for the newer device. <b><i>Conclusion:</i></b> The PrisMax CRRT device outperforms its predecessor with regard to dose delivery and accuracy.
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| 27. |
- Bellomo, R, et al.
(författare)
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Acute kidney injury in sepsis
- 2017
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Ingår i: Intensive care medicine. - : Springer Science and Business Media LLC. - 1432-1238 .- 0342-4642. ; 43:6, s. 816-828
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Tidskriftsartikel (refereegranskat)
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| 28. |
- Broman, M, et al.
(författare)
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The Novel PrisMax Continuous Renal Replacement Therapy System in a Multinational, Multicentre Pilot Setting
- 2018
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 46:3, s. 220-227
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> We assessed how the novel PrisMax continuous renal replacement therapy (CRRT) system performed in a prospective international multicentre setting. We compared this device to its predecessor, the Prismaflex, with regards to multiple treatment parameters. Additionally, we performed a survey, aiming to measure user satisfaction. <b><i>Methods:</i></b> Data was prospectively collected from 7 intensive care units (ICU) in 6 countries. The PrisMax device data logs constituted the raw material. Clinical parameters like treatment time, filter life span, downtime, delivered dose and number and type of alarms were recorded. A user questionnaire was sent out to 3 of the participating ICUs. <b><i>Results:</i></b> Filter life, downtime, blood pump stops, bag changing time and number of malfunction alarms showed significantly improved values compared to the historic Prismaflex data. The survey showed high scores with regards to user friendliness. <b><i>Conclusion:</i></b> The PrisMax CRRT device is safe and outperformed its’ previous generation counterpart in virtually all aspects. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=489213.
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| 30. |
- Chung, SH, et al.
(författare)
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Chronic inflammation in PD patients
- 2003
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Ingår i: Contributions to nephrology. - Basel : KARGER. - 0302-5144. ; 140:140, s. 104-111
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Kashani, K, et al.
(författare)
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Proposal for a New Classification of Solutes of Interest in Uremia and Hemodialysis
- 2023
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 52:3, s. 233-241
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Tidskriftsartikel (refereegranskat)abstract
- Uremic toxins contribute to clinical manifestations of kidney dysfunction. These toxins include organic and inorganic elements or compounds. While the kidney typically clears uremic toxins, gut dysbiosis, and tissue inflammation could lead to increased production of substances that can further the clinical manifestations of uremia. The uremic toxins are quantitatively measurable in biological fluids and have an established relationship with azotemia signs and symptoms. Their elimination is associated with mitigated uremic manifestations, while their administration to the uremic levels leads to uremic signs in animal or human models or in vitro studies. Besides, the uremic toxins have an established and plausible pathophysiologic relationship with uremic manifestations. The previous classification of uremic toxins was mainly focused on the physicochemical characteristics of these substances to divide them into three categories, (1) free water-soluble low-molecular-weight (<500 Da) solutes, (2) protein-bound, water-soluble, low molecular weight (<500 Da), (3) middle molecular weight (>500 Da and <12,000 Da), and (4) high molecular weight (>12,000 Da). Unfortunately, the classification named above was not centered around patient outcomes and quality of life among those with severe kidney failure. Therefore, a panel of experts convened virtually to provide additional insights into the current state and propose a new uremic toxin classification. This article describes the group’s consensus recommendations regarding the new classification of uremic toxins into more clinically oriented categories.
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- Locatelli, F, et al.
(författare)
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The MPO Study: just a European HEMO Study or something very different?
- 2008
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 26:1, s. 100-104
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Tidskriftsartikel (refereegranskat)abstract
- Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.
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| 40. |
- Locatelli, F, et al.
(författare)
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The relationship of NT-proBNP and dialysis parameters with outcome of incident haemodialysis patients: results from the membrane permeability outcome study
- 2013
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 35:1-3, s. 216-223
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. <b><i>Methods:</i></b> N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. <b><i>Results:</i></b> Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. <b><i>Conclusions:</i></b> NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.
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| 44. |
- Ronco, Claudio, et al.
(författare)
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Blood flow distribution in sorbent beds : analysis of a new sorbent device for hemoperfusion
- 2000
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Ingår i: International Journal of Artificial Organs. - 0391-3988 .- 1724-6040. ; 23:2, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- A new polymer-based sorbent cartridge has been recently developed for enhancing middle molecule removal during hemodialysis. The cartridge (Betasorb, Renaltech, New York, USA) has been designed to be placed in series with the dialyzer in the blood circuit. It is therefore important to evaluate the distribution of flow into the blood compartment of the device in order to assess if the surface of the sorbent is utilized to the best. For this purpose, a special imaging technique was utilized. Cartridges were analyzed during a simulated in vitro circulation at 250 and 350 ml/min of blood flow and 25% and 40% hematocrit. Cartridges were placed in vertical position and a cross longitudinal section 1 cm thick was analyzed in sequence by a helical scanner. Dye was injected into the arterial inlet and the progressive distribution was evaluated by sequential densitometrical measures carried out automatically by the machine. The sequential images analyzed by the scanner demonstrated excellent distribution of the flow in the blood compartment with minimal difference between the central and the peripheral regions of the compartment. In particular the following flow velocity pattern could be observed under the different experimental conditions tested. We may conclude that the cartridge design is adequate and no channelling effects could be detected in the blood compartment. The flow distribution is slightly affected by changes in flow rate and hematocrit showing an optimal utilization of the available surface for molecule adsorption.
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- Senore, C, et al.
(författare)
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Performance of colorectal cancer screening in the European Union Member States: data from the second European screening report
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:7, s. 1232-1244
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Tidskriftsartikel (refereegranskat)abstract
- To present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs).DesignCross-sectional study. We analysed key performance indicators—participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC—based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols.ResultsParticipation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%–71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%–66.6%), and it showed a positive correlation (ρ=0.842, p<0.001) with participation in breast cancer screening in the same areas. Screening performance showed a large variability. Compliance with referral for colonoscopy (total colonoscopy (TC)) assessment ranged between 64% and 92%; TC completion rate ranged between 92% and 99%. PR and DR of advanced adenomas and CRC were higher in FIT, as compared with gFOBT programmes, and independent of the protocol among men, older subjects and those performing their first screening.ConclusionsThe variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management.
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