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1.
Biomolecules ; 11(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800255

RESUMO

The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.

2.
Heart ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795382

RESUMO

OBJECTIVE: Decreased kidney function increases cardiovascular risk and predicts poor survival. Estimated glomerular filtration rate (eGFR) by creatinine may theoretically be less accurate in the critically ill. This observational study compares long-term cardiovascular mortality risk by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; Caucasian, Asian, paediatric and adult cohort (CAPA) cystatin C equation and the CKD-EPI combined creatinine/cystatin C equation. METHODS: The nationwide study includes 22 488 intensive care patients in Uppsala, Karolinska and Lund University Hospitals, Sweden, between 2004 and 2015. Creatinine and cystatin C were analysed with accredited methods at admission. Reclassification and model discrimination with C-statistics was used to compare creatinine and cystatin C for cardiovascular mortality prediction. RESULTS: During 5 years of follow-up, 2960 (13 %) of the patients died of cardiovascular causes. Reduced eGFR was significantly associated with cardiovascular death by all eGFR equations in Cox regression models. In each creatinine-based GFR category, 17%, 19% and 31% reclassified to a lower GFR category by cystatin C. These patients had significantly higher cardiovascular mortality risk, adjusted HR (95% CI), 1.55 (1.38 to 1.74), 1.76 (1.53 to 2.03) and 1.44 (1.11 to 1.86), respectively, compared with patients not reclassified. Harrell's C-statistic for cardiovascular death for cystatin C, alone or combined with creatinine, was 0.73, significantly higher than for creatinine (0.71), p<0.001. CONCLUSIONS: A single cystatin C at admission to the intensive care unit added significant predictive value to creatinine for long-term cardiovascular death risk assessment. Cystatin C, alone or in combination with creatinine, should be used for estimating GFR for long-term risk prediction in critically ill.

3.
Sci Rep ; 11(1): 5882, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723337

RESUMO

Decreased glomerular filtration rate (GFR) is linked to poor survival. The predictive value of creatinine estimated GFR (eGFR) and cystatin C eGFR in critically ill patients may differ substantially, but has been less studied. This study compares long-term mortality risk prediction by eGFR using a creatinine equation (CKD-EPI), a cystatin C equation (CAPA) and a combined creatinine/cystatin C equation (CKD-EPI), in 22,488 patients treated in intensive care at three University Hospitals in Sweden, between 2004 and 2015. Patients were analysed for both creatinine and cystatin C on the same blood sample tube at admission, using accredited laboratory methods. During follow-up (median 5.1 years) 8401 (37%) patients died. Reduced eGFR was significantly associated with death by all eGFR-equations in Cox regression models. However, patients reclassified to a lower GFR-category by using the cystatin C-based equation, as compared to the creatinine-based equation, had significantly higher mortality risk compared to the referent patients not reclassified. The cystatin C equation increased C-statistics for death prediction (p < 0.001 vs. creatinine, p = 0.013 vs. combined equation). In conclusion, this data favours the sole cystatin C equation rather than the creatinine or combined equations when estimating GFR for risk prediction purposes in critically ill patients.

5.
Sci Rep ; 11(1): 4236, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608569

RESUMO

Mechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33481246

RESUMO

BACKGROUND: P. aeruginosa possesses antibiotic resistance, making treatment difficult. Polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) have antibacterial effects, but have not been studied in large animal pneumonia. OBJECTIVES: To test if Pa-IgY decreases the concentration of P. aeruginosa in bronchoalveolar lavage in experimental porcine pneumonia over 27 hours. METHOD: Norwegian landrace pigs were anesthetized, mechanically ventilated, and subject to invasive monitoring. The animals were randomized to receive either P. aeruginosa (control, n = 12) or P aeruginosa + Pa-IgY antibodies with a repeated dose of Pa-IgY after 12 hours (intervention, n = 12) in the right lower pulmonary lobe. Bronchoalveolar lavage (BAL) cultures and physiological measurements were obtained repeatedly for 27 hours after which the pigs were sacrificed. RESULTS: BAL bacterial concentration increased in both groups and peaked at 107.28  ± 100.21  CFU/mL in the intervention group vs 107 .36  ± 100.50  CFU/mL in the control group (n.s.). BAL bacterial concentration decreased during the experiment to 105.35  ± 100 .39  CFU/mL in the intervention group vs 105.19  ± 100.37 in the control group (n.s.). The intervention group had lower heart rate (P < .001), lower cardiac index (P < .01), and lower arterial lactate (P < .001) compared to the control group. The core temperature was lower in the intervention group than in the control group (P < .001). CONCLUSION: The chosen dose of Pa-IgY did not decrease concentrations of P. aeruginosa in BAL over 27 hours. We conclude that it is unlikely that there is a large effect of this specific dose and route of administration of Pa-IgY in this type of model.

8.
Physiol Rep ; 9(1): e14700, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33403805

RESUMO

Acute respiratory distress syndrome (ARDS) is associated with diffuse inflammation, alveolar epithelial damage, and leakage of plasma proteins into the alveolar space, which together contribute to inactivation of pulmonary surfactant and respiratory failure. Exogenous surfactant delivery is therefore considered to hold potential for ARDS treatment, but clinical trials with natural derived surfactant or synthetic surfactant containing a surfactant protein C (SP-C) analogue have been negative. Synthetic surfactant CHF5633, containing analogues of SP-B and SP-C, may be effective against ARDS. The aim here was to compare treatment effects of CHF5633 and animal-derived surfactant poractant alfa in animal model of ARDS. ARDS was induced in adult New Zealand rabbits by mild lung lavages followed by injurious ventilation until respiratory failure (P/F ratio <26.7 kPa). The animals were then treated with intratracheal bolus of 200 mg/kg CHF5633 or poractant alfa (Curosurf® ), or air as control. The animals were subsequently ventilated for an additional 4 hr and respiratory parameters were recorded regularly. Postmortem, histological analysis, degree of lung edema, and levels of the cytokines TNFα, IL-6, and IL-8 in lung homogenates were evaluated. Both surfactant preparations improved lung function, reduced the levels of pro-inflammatory cytokines, and degree of lung edema to very similar degrees versus the controls. No significant differences in any of the analyzed parameters were observed between the CHF5633- and poractant alfa-treated groups. This study indicates that single dose of CHF5633 improves lung function and attenuates inflammation as effectively as poractant alfa in experimental ARDS caused by injurious ventilation.

9.
Intensive Care Med Exp ; 9(1): 3, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33496887

RESUMO

BACKGROUND: Bedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lung injury. We propose here a novel operator-independent technique, enabled by a fibre optic oxygen sensor, to quantify the lung volume available for gas exchange. We hypothesised that the continuous measurement of arterial partial pressure of oxygen (PaO2) decline during a breath-holding manoeuvre could be used to estimate lung volume in a single-compartment physiological model of the respiratory system. METHODS: Thirteen pigs with a saline lavage lung injury model and six control pigs were studied under general anaesthesia during mechanical ventilation. Lung volumes were measured by simultaneous PaO2 rate of decline (VPaO2) and whole-lung computed tomography scan (VCT) during apnoea at different positive end-expiratory and end-inspiratory pressures. RESULTS: A total of 146 volume measurements was completed (range 134 to 1869 mL). A linear correlation between VCT and VPaO2 was found both in control (slope = 0.9, R2 = 0.88) and in saline-lavaged pigs (slope = 0.64, R2 = 0.70). The bias from Bland-Altman analysis for the agreement between the VCT and VPaO2 was - 84 mL (limits of agreement ± 301 mL) in control and + 2 mL (LoA ± 406 mL) in saline-lavaged pigs. The concordance for changes in lung volume, quantified with polar plot analysis, was - 4º (LoA ± 19°) in control and - 9° (LoA ± 33°) in saline-lavaged pigs. CONCLUSION: Bedside measurement of PaO2 rate of decline during apnoea is a potential approach for estimation of lung volume changes associated with different levels of airway pressure.

10.
Cytokine ; 138: 155389, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33348065

RESUMO

BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients. METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality. RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality. CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.


Assuntos
Lesão Renal Aguda/patologia , Síndrome da Liberação de Citocina/mortalidade , Citocinas/sangue , Insuficiência Respiratória/patologia , Lesão Renal Aguda/virologia , Idoso , Biomarcadores/sangue , /mortalidade , Estado Terminal , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , /imunologia
11.
Nephron ; : 1-6, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264783

RESUMO

BACKGROUND: Glycated haemoglobin A1c (HbA1c) has limitations as a glycemic marker for patients with diabetes and CKD and for those receiving dialysis. Glycated albumin is an alternative glycemic marker, and some studies have found that glycated albumin more accurately reflects glycemic control than HbA1c in these groups. However, several factors are known to influence the value of glycated albumin including proteinuria. Continuous glucose monitoring (CGM) is another alternative to HbA1c. CGM allows one to assess mean glucose, glucose variability, and the time spent in hypo-, normo-, and hyperglycemia. Currently, several different CGM models are approved for use in patients receiving dialysis; CKD (not on dialysis) is not a contraindication in any of these models. Some devices are for blind recording, while others provide real-time data to patients. Small studies suggest that CGM could improve glycemic control in hemodialysis patients, but this has not been studied for individual CKD stages. SUMMARY: Glycated albumin and CGM avoid the pitfalls of HbA1c in CKD and dialysis populations. However, the value of glycated albumin may be affected by several factors. CGM provides a precise estimation of the mean glucose. Here, we discuss the strengths and limitations for using HbA1c, glycated albumin, or CGM in CKD and dialysis population. Key Messages: Glycated albumin is an alternative glycemic marker but is affected by proteinuria. CGM provides a precise estimation of mean glucose and glucose variability. It remains unclear if CGM improves glycemic control in the CKD and dialysis populations.

12.
J Appl Lab Med ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33274357

RESUMO

BACKGROUND: The need for rapid point-of-care (POC) diagnostics is now becoming more evident due to the increasing need for timely results and improvement in healthcare service. With the recent COVID-19 pandemic outbreak, POC has become critical in managing the spread of disease. Applicable diagnostics should be readily deployable, easy to use, portable, and accurate so that they fit mobile laboratories, pop-up treatment centers, field hospitals, secluded wards within hospitals, or remote regions, and can be operated by staff with minimal training. Complete blood count (CBC), however, has not been available at the POC in a simple-to-use device until recently. The HemoScreen, which was recently cleared by the FDA for POC use, is a miniature, easy-to-use instrument that uses disposable cartridges and may fill this gap. CONTENT: The HemoScreen's analysis method, in contrast to standard laboratory analyzers, is based on machine vision (image-based analysis) and artificial intelligence (AI). We discuss the different methods currently used and compare their results to the vision-based one. The HemoScreen is found to correlate well to laser and impedance-based methods while emphasis is given to mean cell volume (MCV), mean cell hemoglobin (MCH), and platelets (PLT) that demonstrate better correlation when the vision-based method is compared to itself due to the essential differences between the underlying technologies. SUMMARY: The HemoScreen analyzer demonstrates lab equivalent performance, tested at different clinical settings and sample characteristics, and might outperform standard techniques in the presence of certain interferences. This new approach to hematology testing has great potential to improve quality of care in a variety of settings.

13.
Eur Respir J ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334944

RESUMO

BACKGROUND: The current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in intensive care unit are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). METHODS: An international, multicentre, prospective cohort study of patients presenting with hypoxemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with PaO2/FiO2 ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure (PEEP) of at least 5 cm H2O. ICU prevalence, causes of hypoxemia, hospital survival, factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. FINDINGS: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (8.2%, CHF). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1%versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality but similar adjusted mortality than ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only 2 quadrants involved. INTERPRETATION: More than one third of the patients receiving mechanical ventilation have hypoxaemia and new infiltrates with an hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

14.
Nutrients ; 12(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317156

RESUMO

A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 µg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.

15.
Crit Care ; 24(1): 646, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33189146

RESUMO

BACKGROUND: Sepsis is often treated with penicillin-binding protein 3 (PBP-3) acting ß-lactam antibiotics, such as piperacillin-tazobactam, cefotaxime, and meropenem. They cause considerable bacterial structural changes and have in vitro been associated with an increased inflammatory response. In a clinically relevant large animal sepsis model, our primary aim was to investigate whether bacteria killed by a PBP-3-active antibiotic has a greater effect on the early inflammatory response and organ dysfunction compared with corresponding amounts of live or heat-killed bacteria. A secondary aim was to determine whether the addition of an aminoglycoside could mitigate the cefuroxime-induced response. METHOD: Killed or live Escherichia coli were administrated as a 3-h infusion to 16 healthy pigs in a prospective, randomized controlled interventional experimental study. Cefuroxime was chosen as the PBP-3-active antibiotic and tobramycin represented the aminoglycosides. The animals were randomized to receive (I) bacteria killed by cefuroxime, (II) live bacteria, (III) bacteria killed by heat, or (IV) bacteria killed by the combination of cefuroxime and tobramycin. Plasma endotoxin, tumor necrosis factor alpha, interleukin-6, interleukin-10, leukocytes, and organ function were recorded at the start of the experiment and then hourly for 6 h. RESULTS: Differences in dynamics of concentration over time between the four treatment groups were found for the three cytokines (p < 0.001). Animals receiving cefuroxime-killed bacteria demonstrated higher responses than those receiving live (p < 0.05) or heat-killed bacteria (p < 0.01). The addition of tobramycin reduced the cefuroxime-induced responses (p < 0.001). The cytokine responses were associated with leucocyte activation that was further associated with pulmonary dysfunction and increases in lactate (p < 0.01). CONCLUSIONS: In comparison with live or heat-killed bacteria, bacteria killed by a PBP-3-active antibiotic induced an increased inflammatory response that appears to be associated with deteriorated organ and cellular function. The addition of an aminoglycoside to the PBP-3-active antibiotic reduced that response.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33190222

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID-19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk. METHODS: In a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM-1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP-2) were analysed in 52 patients at admission. The majority (n = 51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n = 37, 65%), whereas stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30-day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n = 9 (17%) patients. CONCLUSIONS: A majority of patients with COVID-19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.

17.
Ann Intern Med ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33166224

RESUMO

BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation. SETTING: Research and clinical studies (n = 13) with measured GFR available. PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). MEASUREMENTS: Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. RESULTS: The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. LIMITATION: No Black patients were included. CONCLUSION: The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. PRIMARY FUNDING SOURCE: Swedish Research Council (Vetenskapsrådet).

18.
Kidney Int ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33157151

RESUMO

The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.

19.
Clin Lab ; 66(11)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33180419

RESUMO

BACKGROUND: In a heterogenous group of patients with acute headache it is important to diagnose subarachnoid hemorrhage (SAH), a potentially lethal but treatable condition, with short turnaround time and high precision. Spectrophotometry of cerebrospinal fluid (CSF) is an essential part in the investigation of patients with suspected SAH but the analysis is slow and operator dependent. METHODS: We have evaluated a new instrument for ultraviolet and visible light (UV-VIS) spectroscopy (DrugLog©, Pharmacolog, Uppsala, Sweden) for automatic determination of oxyhemoglobin and bilirubin in CSF samples. The instrument incorporates software for calculating the absorbance values thus eliminating operator bias. Bilirubin and oxyhemoglobin in CSF was analyzed both with DrugLog© and traditional spectrophotometry at 415 and 476 nanometers (A415 and A476) using patient samples containing varying amounts of bilirubin and oxyhemoglobin. RESULTS: The DrugLog© method showed a strong correlation both for bilirubin (Pearson's r = 0.996) and oxyhemo-globin (Pearson's r = 0.993). The DrugLog© method had good linearity and precision, offering an automated determination of bilirubin and oxyhemoglobin, eliminating operator bias. CONCLUSIONS: The DrugLog© instrument has a short assay time and showed good agreement with traditional spectrophotometry.

20.
Physiol Meas ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049721

RESUMO

The acute respiratory distress syndrome is associated with a high rate of morbidity and mortality, as patients undergoing mechanical ventilation are at risk of ventilator-induced lung injuries. OBJECTIVE: To measure the lung heterogeneity and deadspace volume to find safer ventilator strategies. Then, the ventilator settings could offer homogeneous ventilation and theoretically equalise and reduce tidal strain/stress in the lung parenchyma. APPROACH: The Inspired Sinewave Test (IST) is a non-invasive lung measurement tool, which does not require patients' cooperation. The IST can measure the effective lung volume, pulmonary blood flow and deadspace volume. We developed a computational simulation of the cardiopulmonary system to allow lung heterogeneity to be quantified using data solely derived from the IST. Then, the method to quantify lung heterogeneity using two IST tracer gas frequencies (180s and 60s) was introduced and experimented in the simulation lungs and in animal models. Thirteen anaesthetised pigs were studied with the IST, both before and after experimental lung injury (saline-lavage ARDS model). The deadspace volume is compared between IST and the SF_{6} Washout method. RESULTS: The IST could measure the lung heterogeneity using two frequencies tracer gases. Furthermore, the value of IST ventilation heterogeneity in ARDS lungs were higher than in control lungs at PEEP 10cmH_{2}O (AuC=0.85, p<0.001). Deadspace volume values measured by the IST has a strong relationship with the measured values of the SF_{6} (9mL bias and limits of agreement from -79mL to 57mL in control animals). SIGNIFICANCE: the potential impact of the IST technique in the identification of ventilation and perfusion heterogeneity during ventilator support.

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