| 1. |
- Sylvan, Sandra Eketorp, et al.
(author)
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First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
- 2019
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In: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
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| 2. |
- Artursson, Karin, et al.
(author)
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Foodborne pathogens in unpasteurized milk in Sweden
- 2018
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In: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605 .- 1879-3460. ; 284, s. 120-127
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Journal article (peer-reviewed)abstract
- Raw milk may be a risk for public health if it is contaminated with zoonotic pathogens. To study the prevalencein unpasteurized milk from Swedish farms, bovine and small ruminant dairy farms were sampled. Since thesampling method and transport conditions may influence the outcome of analyses, efforts were made to optimizethe methodology. Culturing of bacteria was done from in-line milk filters collected from the milk pipe at thepoint where it enters the milk bulk tank at the farms and this way of sampling was compared to sampling bulktank milk (BTM) directly. Analysing milk filters were found to be superior to analysing BTM directly. Conditionsfor transport of milk filter samples were further improved by the addition of Cary Blair transport medium, whichsignificantly increased the number of positive samples for pathogenic bacteria. The isolation of several foodbornepathogens from milk filters was demonstrated. The prevalence of samples with Staphylococcus aureus was71% and 64%, and Listeria spp. 21% and 29% from dairy cow and goat/sheep farms, respectively. Campylobacterjejuni, Yersinia enterocolitica and verotoxigenic Escherichia coli (VTEC) O157 were detected in 9%, 2% and 2% ofsamples from bovine milk, respectively.We conclude that the choice of sampling method and sample handling influence the results of bacterialculturing. From the results of this study, we strongly recommend to sample in-line milk filters instead of BTMdirectly and to use Cary Blair medium during transport, especially if the samples are to be analysed forCampylobacter spp. and/or Listeria spp. The findings also show that unpasteurized milk from Swedish farmsoccasionally contain bacteria with zoonotic potential.
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| 3. |
- Birchenough, George M. H., et al.
(author)
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New developments in goblet cell mucus secretion and function
- 2015
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In: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:4, s. 712-719
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Research review (peer-reviewed)abstract
- Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell that can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example, after endocytosis or in response to acetyl choline. However, despite much progress in recent years, our understanding of goblet cell function and regulation is still in its infancy.
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| 4. |
- Borgström, Kristina, et al.
(author)
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Toddlers’ shape recognition predicts language and working memory at 6-7 years
- 2017
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Conference paper (peer-reviewed)abstract
- An electrophysiological measure of semantic processing (the N400) was used to assess shape recognition in toddlers. This measure strongly predicted working memory at 6-7 years. Moreover, a behavioral measure of shape recognition at 24 months was related to concurrent vocabulary and vocabulary skills at 6-7 years.
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| 5. |
- Braekeveldt, Noémie, et al.
(author)
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Patient-derived xenograft models reveal intratumor heterogeneity and temporal stability in neuroblastoma
- 2018
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In: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
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Journal article (peer-reviewed)abstract
- Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain underexplored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research.
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| 6. |
- Brook, Adam, et al.
(author)
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Cell free hemoglobin in the fetoplacental circulation : A novel cause of fetal growth restriction?
- 2018
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In: FASEB Journal. - 0892-6638. ; 32:10, s. 5436-5446
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Journal article (peer-reviewed)abstract
- Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGRfetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation,which occurs in adults.During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance (P<0.05). fHbF sequesteredNOinacute andchronic exposuremodels (P<0.001), andfHbF-primed placental endothelial cellsdevelopedaproinflammatoryphenotype,demonstratedby activationofNF-κBpathway, generation of IL-1α and TNF-α (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection.Thisunrecognizedmechanismfor fetal compromise offers a novel insight into FGRaswell as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.
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| 7. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 8. |
- Danielsbacka, Jenny S, et al.
(author)
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Lung function, functional capacity, and respiratory symptoms at discharge from hospital in patients with acute pulmonary embolism: A cross-sectional study.
- 2018
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In: Physiotherapy theory and practice. - : Informa UK Limited. - 1532-5040 .- 0959-3985. ; 34:3, s. 194-201
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Journal article (peer-reviewed)abstract
- Acute pulmonary embolism (PE) is a cardiovascular disease with symptoms including respiratory associated chest pain (RACP) and dyspnea. No previous studies exist focusing on lung function, functional capacity, and respiratory symptoms at discharge after PE.The aim was to examine and describe lung function, functional capacity, and respiratory symptoms at discharge in patients with PE and compare to reference values.Fifty consecutive patients with PE admitted to the Acute Medical Unit, Sahlgrenska University Hospital, were included. Size of PE was calculated by Qanadli score (QS) percentage (mean QS 33.4% (17.6)). FVC and FEV1 were registered and 6-minute walk test (6MWT) performed at the day of discharge. RACP was rated before and after spirometry/6MWT with the Visual Analogue Scale. Perceived exertion was rated with Borg CR-10 scale. Spirometry and 6MWT results were compared with reference values.This study shows that patients with PE have significantly reduced lung function (p<0.05) and functional capacity (p<0.001) at discharge compared with reference values. Patients with higher QS percentage were more dyspneic after 6MWT, no other significant differences in lung function or functional capacity were found between the groups. The patients still suffer from RACP (30%) and dyspnea (60%) at discharge.This study indicates that patients with PE have a reduced lung function, reduced functional capacity, and experience respiratory symptoms as pain and dyspnea at discharge. Further studies are needed concerning long-term follow-up of lung function, functional capacity, and symptoms after PE.
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| 9. |
- Danielsson, Helena, et al.
(author)
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Persistent organic pollutants in Swedish mosses
- 2016
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Reports (other academic/artistic)abstract
- On behalf of the Swedish Environmental Protection Agency, IVL Swedish Environmental Research Institute led in 2015 a project aiming to examine the concentrations of persistent organic pollutants (POPs) in mosses. Samples of red-stemmed feathermoss (Pleurozium schreberi) and glittering wood moss (Hylocomium splendens) were collected at 83 rural sampling sites. Of these, 20 samples were analysed for the following groups: polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), selected organochlorine pesticides, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), dioxins and furans (PCDD/PCDFs), dioxin-like PCBs and perfluorinated alkylated substances (PFAS). The sampling sites were selected to cover the whole of Sweden, in both the north-south gradient and in the east-west gradient. The sites were also chosen to represent both eventually elevated concentrations as well as low concentrations of POPs. Information on locations of industrial activities, population density and monitoring stations for organic substances in air and precipitation (Swedish national monitoring programme) were also used for the selection of sampling sites. Generally, the concentrations of the analysed substances were very low, often close to or below the quantification limits for the analyses. Significant correlation was found between the concentrations of PAHs, dioxin/furans and dioxin like PCBs in the mosses and the distance to the closest industry, and also to the distance from the southernmost point in Sweden. p,p-DDE concentrations in mosses showed a correlation to the distance from the southernmost point in Sweden, with the highest concentrations in the south. No correlation was found between the concentrations of p,p-DDE (one of the DDTs) in mosses and distance to the closest industry. The concentrations of PAHs in mosses collected at sites located in the vicinity of three air monitoring stations (Råö, Aspvreten and Pallas) were in agreement with the concentrations of PAHs in air, with the highest concentrations in mosses and in air found in the south and the lowest in the north. Comparison between the PAH profile in air and in mosses showed a higher percentage of heavier PAHs in the mosses. This indicates a larger proportion of particular bounded PAHs in mosses. HBCDD and PFAS were not detected in any of the analysed moss samples, which is consistent with a similar study conducted in Norway.
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| 10. |
- Engström, Gunnar, et al.
(author)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Journal article (peer-reviewed)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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