| 1061. |
- Lipcsey, Miklos, et al.
(författare)
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The brain is a source of S100B increase during endotoxemia in the pig
- 2010
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Ingår i: Anesthesia and Analgesia. - 0003-2999 .- 1526-7598. ; 110:1, s. 174-180
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.METHODS:Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg-1 · h-1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.RESULTS: In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).CONCLUSIONS:Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.
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| 1062. |
- Lipcsey, Miklós, et al.
(författare)
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The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge
- 2019
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 25:6, s. 369-373
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Tidskriftsartikel (refereegranskat)abstract
- Plasma calprotectin has previously been reported as a biomarker for sepsis. The aim of the present study was to elucidate the kinetics of calprotectin release from neutrophils exposed to Escherichia coli and endotoxin. Whole blood samples were exposed to E. coli bacteria or endotoxin in vitro. Blood samples were collected after 0, 1, 2, 3 and 4 h and plasma calprotectin was analysed by particle enhanced turbidimetric immunoassay while TNF-α, IL-6, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were analyzed by ELISA. When neutrophils were exposed to either E. coli or endotoxin, calprotectin levels began to increase within a couple of hours after the challenge. Calprotectin increases early in response to bacterial challenge. Given the logistic advantages of the calprotectin analysis, this may be of interest for early diagnosis of bacterial infections.
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| 1063. |
- Lipcsey, Miklós, et al.
(författare)
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Urine Hydrogen Peroxide Levels and Their Relation to Outcome in Patients with Sepsis, Septic Shock, and Major Burn Injury
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogen peroxide (H2O2) and oxidative stress have been suggested as possible instigators of both the systemic inflammatory response and the increased vascular permeability associated with sepsis and septic shock. We measured H2O2 concentrations in the urine of 82 patients with severe infections, such as sepsis, septic shock, and infections not fulfilling sepsis-3 criteria, in patients with major burn injury with associated systemic inflammation, and healthy subjects. The mean concentrations of H2O2 were found to be lower in patients with severe infections compared to burn injury patients and healthy subjects. Patients with acute kidney injury (AKI), vs. those without AKI, in all diagnostic groups displayed higher concentrations of urine H2O2 (p < 0.001). Likewise, urine concentrations of H2O2 were higher in non-survivors as compared to survivors (p < 0.001) at day 28 in all diagnostic groups, as well as in patients with severe infections and burn injury (p < 0.001 for both). In this cohort, increased H2O2 in urine is thus associated with mortality in patients with sepsis and septic shock as well as in patients with burn injury.
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| 1064. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma : Can the response be predicted?
- 2022
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Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis Group. - 2164-5515 .- 2164-554X. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: After trauma and central nervous system (CNS) injury, trauma-induced immune deficiency syndrome (TIDS) and CNS injury-induced immune deficiency syndrome (CIDS) may negatively affect responses to T-cell-dependent vaccines, such as pneumococcal conjugate vaccine (PCV) recommended after basilar fracture. This study (NCT02806284) aimed to investigate whether there after neurotrauma is a correlation between T-cell-dependent and independent vaccine responses and, thus, if B-cell activity is similarly depressed and whether the T-cell-dependent response is possible to predict.Method: Adult patients with basilar fracture (n = 33) and those undergoing pituitary gland surgery (n = 23) were within 10 days vaccinated with a T-cell-dependent vaccine against Haemophilus influenzae type b (Hib) and a T-cell-independent pneumococcal polysaccharide vaccine (PPSV). Samples reflecting the systemic inflammatory response and pre- and post-vaccination antibody levels after 3–6 weeks against Hib and PPSV were collected and determined by enzyme immunoassays.Results: High and significant correlations were detected in the responses to different pneumococcal serotypes, but none between the Hib and PPSV responses. No differences in trauma scores, C-reactive protein, IL-6, IL-10, pentraxin 3, fractalkine or calprotectin plasma concentrations or in ex vivo TNF-α, IL-6 or IL-10 responses to endotoxin were found between Hib vaccination responders and non-responders.Conclusions: There was no correlation between the pneumococcal responses and that to Hib, indicating that B-cell function is not similarly depressed as T-cell function. Grading of the trauma or parameters reflecting the innate immune response could not predict the T-cell-dependent vaccine response. There is a need of further studies evaluating the vaccine response after neurotrauma.
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| 1065. |
- Lo Mauro, Antonella
(författare)
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Clinical and experimental studies on the diaphragm during physiological and pathophysio-logical conditions
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The diaphragm is the most important respiratory muscle. It separates the thorax from the abdomen and it is innervated by phrenic nerve. The action of the diaphragm strongly depends on the combination of: the conductivity of the phrenic nerve; b) the developed force (pressure); c) the length at which it contracts; d) the velocity of short- ening and e) the level of activation.The general aim of this doctoral thesis is to study the diaphragm in different conditions in which different mechanical loads and/or different agents modified one or more of these factors in order to understand how the diaphragm copes with anesthesia, phrenic nerve injury, severe lung diseases and increasing abdominal load.In Study I, the movement induced by the diaphragm on tumor marker surrogate, being a source of noise while planning target volume during stereotactic body radiation ther- apy was quantified. High Frequency Jet Ventilation at a frequency of 200 min-1 seemed to be the best compromise between immobilization and gas exchange.In Study II, the role of the diaphragm during the emergence from anesthesia (namely, propofol) was investigated, finding no contribution because of active contraction of the expiratory muscles in this phase, presumably triggered by the resistance in the tracheal tube.In Study III, an animal model (porcine) of phrenic nerve damage was created and the compensatory mechanisms of non-diaphragmatic respiratory muscles studied. A 12- fold augmentation of the drive to ribcage muscles occurred during inspiration, while it almost doubled for abdominal muscles during expiration. Increasing level of pres- sure support ventilation masked these respiratory muscles strategy.Study IV described, within an integrated multidisciplinary longitudinal study, differ- ent functional aspects (geometry, weakness, force, mobility, contractility, electrical activity and kinematics) of the diaphragm before and after lung transplantation. A subclinical diaphragmatic dysfunction occurs after surgery, despite appropriate clini- cal course and respiratory outcome, induced by phrenic nerve neurapraxia secondary to surgical procedure.Study V was a non-invasive and longitudinal study of the progressive changes of the diaphragm during healthy pregnancy. During pregnancy, the diaphragm is condi- tioned to optimize its active role provided during parturition, as its co-contraction with abdominal muscles plays a fundamental role in the phase of baby expulsion.
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| 1066. |
- Lo Mauro, Antonella, et al.
(författare)
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Comparison of different methods for lung immobilization in an animal model
- 2020
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 150, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Respiratory-induced motion introduces uncertainties in the delivery of dose in radiotherapy treatments. Various methods are used clinically, e.g. breath-holding, while there is limited experience with other methods such as apneic oxygenation and high frequency jet ventilation (HFJV). This study aims to compare the latter approaches for lung immobilization and their clinical impact on gas exchange in an animal model.MATERIALS AND METHODS: Two radiopaque tumor surrogate markers (TSM) were placed in the central (cTSM) and peripheral (dTSM) regions of the lungs in 9 anesthetized and muscle relaxed pigs undergoing 3 ventilatory interventions (1) HFJV at rates of 200 (JV200), 300 (JV300) and 400 (JV400) min-1; (2) apnea at continuous positive airway pressure (CPAP) levels of 0, 8 and 16 cmH2O; (3) conventional mechanical ventilation (CMV) as reference mode. cTSM and dTSM were visualized using fluoroscopy and their coordinates were computed. The ventilatory pattern was registered, and oxygen and carbon dioxide (pCO2) partial pressures were measured.RESULTS: The highest range of TSM motion, and ventilation was found during CMV, the lowest during apnea. During HFJV the amount of motion varied inversely with increasing frequency. The reduction of TSM motion at JV300, JV400 and all CPAP levels came at the cost of increased pCO2, however the relatively low frequency of 200 min-1 for HFJV was the only ventilatory setting that enabled adequate CO2 removal.CONCLUSION: In this model, HFJV at 200 min-1 was the best compromise between immobilization and gas exchange for sessions of 10-min duration.
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| 1067. |
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| 1068. |
- Lundblad, Katarina, et al.
(författare)
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CSF Concentrations of CXCL13 and sCD27 Before and After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.
- 2023
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Ingår i: Neurology. - 2332-7812. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: In the past decade, autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a treatment for relapsing-remitting multiple sclerosis (RRMS). How this procedure affects biomarkers of B- and T-cell activation is currently unknown. The objective of this study was to investigate CXCL13 and sCD27 concentrations in CSF before and after AHSCT.METHODS: This prospective cohort study was conducted at a specialized MS clinic in a university hospital. Patients with a diagnosis of RRMS, treated with AHSCT between January 1, 2011, and December 31, 2018, were evaluated for participation. Patients were included if CSF samples from baseline plus at least 1 follow-up were available on June 30, 2020. A control group of volunteers without neurologic disease was included as a reference. CSF concentrations of CXCL13 and sCD27 were measured with ELISA.RESULTS: The study comprised 29 women and 16 men with RRMS, aged 19-46 years at baseline, and 15 women and 17 men, aged 18-48 years, in the control group. At baseline, patients had higher CXCL13 and sCD27 concentrations than controls, with a median (IQR) of 4 (4-19) vs 4 (4-4) pg/mL (p < 0.0001) for CXCL13 and 352 (118-530) vs 63 (63-63) pg/mL (p < 0.0001) for sCD27. After AHSCT, the CSF concentrations of CXCL13 were considerably lower at the first follow-up at 1 year than at baseline, with a median (IQR) of 4 (4-4) vs 4 (4-19) pg/mL (p < 0.0001), and then stable throughout follow-up. The CSF concentrations of sCD27 were also lower at 1 year than at baseline, with a median (IQR) of 143 (63-269) vs 354 (114-536) pg/mL (p < 0.0001). Thereafter, sCD27 concentrations continued to decrease and were lower at 2 years than at 1 year, with a median (IQR) of 120 (63-231) vs 183 (63-290) pg/mL (p = 0.017).DISCUSSION: After AHSCT for RRMS, CSF concentrations of CXCL13 were rapidly normalized, whereas sCD27 decreased gradually over the course of 2 years. Thereafter, the concentrations remained stable throughout follow-up, indicating that AHSCT induced long-lasting biological changes.
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| 1069. |
- Lundgren, Morgan, et al.
(författare)
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Interlaboratory variation for NT-proBNP among Swedish laboratories in an external quality program 2011-2021
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:9, s. 1643-1651
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients.Methods: Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP.Results: Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median.Conclusions: The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.
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| 1070. |
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