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- Bandert, Anna, et al.
(författare)
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Different distances between central venous catheter tips can affect antibiotic clearance during continuous renal replacement therapy
- 2024
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Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few.METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05.RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02).CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.
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| 3. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
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Tidskriftsartikel (refereegranskat)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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| 4. |
- Bülow Anderberg, Sara
(författare)
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Inflammatory aspects of acute kidney injury development during severe infections
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19.The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19.We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone.The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development.Human neutrophil lipocalin is a neutrophil granular protein. It was used to first evaluate neutrophil reactivity by measuring its concentration after ex vivo stimulation and second systemic activity by estimating its concentration in plasma. In turn the association with renal dysfunction in severe COVID-19 was explored. Increased concentrations in both instances were linked to a greater risk of developing severe acute kidney injury.Lastly, the effect of dexamethasone, another glucocorticoid, on AKI development and neutrophil extracellular markers including histones and myeloperoxidase-DNA in critical COVID-19 was investigated. Dexamethasone was associated with lower AKI incidence and reduced extracellular trap formation.
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| 5. |
- Venge, Per, et al.
(författare)
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Plasma Biomarkers Associated to Outcome in Patients with Sars-Cov-2 Infection
- 2024
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Ingår i: Journal of Clinical and Laboratory Medicine. - : Sci Forschen, Inc.. - 2572-9578. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A serious consequence of respiratory infections with SARS-CoV-2 is Acute Kidney Injury (AKI). The aim of this study was to evaluate some novel biomarkers measured in plasma for their associations with the outcome of this infection as to AKI and mortality. Methods: Four different HNL (Human Neutrophil Lipocalin) assays were constructed using different antibody configurations, reflecting both neutrophil and epithelial cell activities. TK-1 (Thymidine kinase-1) was measured as a sign of cell destruction and proliferation. For comparison the plasma concentrations of NGAL (Neutrophil Gelatinase Associated Lipocalin), the cytokines IL-6, IL-8 and IFN-γ and of cystatin C, and procalcitonin were also measured. One hundred and three patients with severe respiratory failure admitted to the ICU were sampled for blood at admittance and at day three (n=67) after admittance. Results: Sixty-five percent of the patients developed AKI. The performance of the HNL assay 763/8F was most closely associated to outcome as to AKI and mortality with Area Under the Receiver Operating Characteristics Curve (AUC) of 0.87 and a sensitivity of 80% and a specificity of 88% in COVID-19 patients with and without severe AKI (p<0.0001). TK-1 was significantly related to the development of AKI (p=0.01) and the three cytokines were related to mortality (p=0.004-p<0.001). Conclusion: The HNL variant 763/8F and TK-1 are novel biomarkers that might become useful and novel tools in the management of COVID-19 patients, but likely also in other patients affected by AKI.
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| 6. |
- Xu, Shengyuan, et al.
(författare)
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The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus
- 2024
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.
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