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- Iorizzo, L., et al.
(författare)
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Proposed cutoff for fetal scalp blood lactate in intrapartum fetal surveillance based on neonatal outcomes: a large prospective observational study
- 2022
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:4, s. 636-646
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate®/StatstripXpress® Lactate system, the only POC designed for hospital use. Design: Observational study. Setting: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. Population: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0weeks of gestation. Method: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25minutes from FBS to delivery were included in the final calculations. Main outcome measures: Metabolic acidosis in cord blood defined as pH <7.05 plus BDecf >10mmol/l and/or lactate >10mmol/l. Results: A total of 3334 women were enrolled of whom 799 were delivered within 25minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77–0.97), cutoff 5.7mmol/l; pH <7.0 AUC 0.83 (95% CI 0.68–0.97), cutoff 4.6mmol/l; pH <7.05 plus BDecf ≥12mmol/l AUC 0.97 (95% CI 0.92–1), cutoff 5.8mmol/l; Apgar score <7 at 5minutes AUC 0.74 (95% CI 0.63–0.86), cutoff 5.2mmol/l; and pH <7.10 plus composite neonatal outcome AUC 0.76 (95% CI 0.67–0.85), cutoff 4.8mmol/l. Conclusion: A scalp lactate level <5.2mmol/l using the StatstripLactate®/StatstripXpress® system will safely rule out fetal metabolic acidosis. Tweetable abstract: Scalp blood lactate <5.2mmol/l using the StatstripLactate®/StatstripXpress system has an excellent ability to rule out fetal acidosis.
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- Frankel, R., et al.
(författare)
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Autocatalytic amplification of Alzheimer-associated A beta 42 peptide aggregation in human cerebrospinal fluid
- 2019
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is linked to amyloid beta (A beta) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of A beta aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of A beta 42 in human CSF through kinetic experiments at several A beta 42 monomer concentrations (0.8-10 mu M). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF.
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- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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