| 1. |
- Nilsson, Erik, 1975-, et al.
(författare)
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Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up-A CLARICOR Trial Sub-Study
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.
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| 2. |
- Bergman, Lina, 1982, et al.
(författare)
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Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
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Tidskriftsartikel (refereegranskat)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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| 3. |
- Larsson, Anders, et al.
(författare)
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Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:2, s. 156-161
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is the most frequent cause of death in the intensive care unit (ICU). A rapid and correct diagnosis and initiation of therapy is crucial for improving patient outcomes. The aim of this study was to compare the performance of calprotectin with the more widely used sepsis biomarker procalcitonin (PCT) in ICU patients. The performance of calprotectin and PCT as sepsis and prognostic markers for 30-d mortality was compared in a prospective, observational study in an eight-bed ICU. We investigated concentrations of the biomarkers in plasma collected at admission from all ICU patients admitted during a year (2012-2013, n = 271) together with simplified acute physiology 3 scores (SAPS3) and sequential organ failure assessment (SOFA) scores. The receiver operating characteristic (ROC) analysis showed a higher area under the curve (AUC) value for calprotectin (0.79) than for PCT (0.49) when used as a sepsis marker. The calprotectin concentrations at admission were higher in non-survivors than in survivors at day 30. In our study, calprotectin was superior to PCT for distinguishing between ICU patients with sepsis and non-sepsis patients. Calprotectin also had higher predictive ability regarding 30-d mortality.
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| 4. |
- Lipcsey, Miklós, et al.
(författare)
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Endotoxin removal in septic shock with the Alteco LPS adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial-the asset study
- 2020
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 54:2, s. 224-231
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed.Methods: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients.Results: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups.Conclusions: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.
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| 5. |
- Panezai, Jeneen, et al.
(författare)
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Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients
- 2020
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Ingår i: Cytokine. - : Elsevier. - 1043-4666 .- 1096-0023. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic immuno-inflammatory conditions with osteolysis being a hallmark feature. The influence of PD on RA's systemic inflammatory status and disease activity remains unclear. The objective of this study was to assess the systemic inflammation and disease activity of RA under the influence of PD.METHODS: In this case-control study, 38 RA patients (19 with PD and 19 without PD) were compared to 38 non-RA patients and 12 healthy controls. Periodontal parameters (bleeding on probing (BOP), probing pocket depth (PPD), PPD Total, PPD Disease and marginal bone loss (MBL) were determined. Serological analyses included quantification of 92 inflammatory biomarkers using a multiplex proximity extension assay, anti-citrullinated protein antibodies (ACPA), rheumatoid factor (IgM-RF) and erythrocyte sedimentation rate (ESR). RA disease activity was determined using Disease Activity Score for 28 joints (DAS28). All RA patients were on medication.RESULTS: IgM-RF was higher in RA patients with PD. PD conditions were more severe in the non-RA group. Inflammatory biomarkers (IL-10RB, IL-18, CSF-1, NT-3, TRAIL, PD-L1, LIF-R, SLAMF1, FGF-19, TRANCE, CST5, STAMPB, SIRT2, TWEAK, CX3CL1, CXCL5, MCP-1) were significantly higher in RA patients with PD than RA without PD. DAS28 associated with twice as many inflammatory biomarkers in RA patients with PD whereas IgM-RF and ACPA associated more frequently with biomarkers in the RA without PD group. IgM-RF correlated inversely with BOP.CONCLUSION: Periodontal disease augments systemic inflammation in RA. A profound influence exists independent of autoimmune status.
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| 6. |
- Pellegrini, Mariangela, et al.
(författare)
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Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse.
- 2020
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Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 201:10, s. 1218-1229
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL.Objectives: To assess whether external expiratory resistances 1) affect expiratory diaphragmatic contraction during spontaneous breathing, 2) reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants, and 3) reduce tidal atelectasis, preventing hyperinflation.Methods: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. On the basis of computed tomography scans, four lung compartments-not inflated (atelectasis), poorly inflated, normally inflated, and hyperinflated-were defined.Measurements and Main Results: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1) the expiratory transdiaphragmatic pressure decreased during spontaneous breathing by >10%, 2) expiratory flow was reduced and the expiratory time constants became more homogeneous, and 3) the amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation.Conclusions: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.
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| 7. |
- Stattin, Karl, et al.
(författare)
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Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients
- 2020
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Ingår i: Journal of critical care. - : Elsevier BV. - 0883-9441 .- 1557-8615. ; 60, s. 249-252
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.MATERIAL AND METHODS: We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously).RESULTS: Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.CONCLUSIONS: Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.
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| 8. |
- Wändell, P., et al.
(författare)
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TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department
- 2020
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:10, s. 1145-1150
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function.AIM: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea.POPULATION AND METHODS: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP.RESULTS: Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56).CONCLUSIONS: We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.
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| 9. |
- Scaramuzzo, Gaetano, et al.
(författare)
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Influence of Positive End-Expiratory Pressure Titration on the Effects of Pronation in Acute Respiratory Distress Syndrome : A Comprehensive Experimental Study
- 2020
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Ingår i: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Prone position can reduce mortality in acute respiratory distress syndrome (ARDS), but several studies found variable effects on oxygenation and lung mechanics. It is unclear whether different positive end-expiratory pressure (PEEP) titration techniques modify the effect of prone position. We tested, in an animal model of ARDS, if the PEEP titration method may influence the effect of prone position on oxygenation and lung protection. In a crossover study in 10 piglets with a two-hit injury ARDS model, we set the "best PEEP" according to the ARDS Network low-PEEP table (BPARDS) or targeting the lowest transpulmonary driving pressure (BPDPL). We measured gas exchange, lung mechanics, aeration, ventilation, and perfusion with computed tomography (CT) and electrical impedance tomography in each position with both PEEP titration techniques. The primary endpoint was the PaO2/FiO(2) ratio. Secondary outcomes were lung mechanics, regional distribution of ventilation, regional distribution of perfusion, and homogeneity of strain derived by CT scan. The PaO2/FiO(2) ratio increased in prone position when PEEP was set with BPARDS [difference 54 (19-106) mmHg, p = 0.04] but not with BPDPL [difference 17 (-24 to 68) mmHg, p = 0.99]. The transpulmonary driving pressure significantly decreased during prone position with both BPARDS [difference -0.9 (-1.5 to -0.9) cmH(2)O, p = 0.009] and BPDPL [difference -0.55 (-1.6 to -0.4) cmH(2)O, p = 0.04]. Pronation homogenized lung regional strain and ventilation and redistributed the ventilation/perfusion ratio along the sternal-to-vertebral gradient. The PEEP titration technique influences the oxygenation response to prone position. However, the lung-protective effects of prone position could be independent of the PEEP titration strategy.
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| 10. |
- Zamaratskaia, Galia, et al.
(författare)
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Consumption of whole grain/bran rye instead of refined wheat decrease concentrations of TNF-R2, e-selectin, and endostatin in an exploratory study in men with prostate cancer
- 2020
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 39:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. Methods: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. Results: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. Conclusions: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.
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