| 501. |
- Swahn, Fredrik, et al.
(författare)
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Rendezvous cannulation technique reduces post-ERCP pancreatitis : a prospective nationwide study of 12,718 ERCP procedures
- 2013
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 108:4, s. 552-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to investigate if intraoperative rendezvous cannulation reduces the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) because there is no universal consensus on the optimal treatment of common bile duct stones.METHODS: We performed a nationwide case-control study, nested within the cohort of ERCP procedures reported to the Swedish Registry for Gallstone Surgery and ERCP (GallRiks), between 2007 and 2009. Data were collected prospectively from a web-based registry of ERCP procedures that includes variables such as patient characteristics, indication, cannulation technique, diagnostic findings, therapeutic measures, and complications. The primary outcome was PEP.RESULTS: The registry included 12,718 ERCP procedures performed on patients without a history of previous ERCP. The risk of PEP when using the rendezvous technique compared with those who were cannulated by conventional means was reduced from 3.6 to 2.2% (odds ratio (OR) 0.5, 95% confidence interval 0.2-0.9, P=0.02). Although a significant reduction there are overall relatively few cases with PEP and the calculated numbers needed to treat to avoid one case of PEP is as high as 71. Other factors associated with increased risk of PEP were young age, prolonged procedure time, and elective ERCP.CONCLUSIONS: Rendezvous bile duct cannulation during ERCP reduces the risk of PEP from 3.6 to 2.2% compared with conventional biliary cannulation.
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| 502. |
- Swartling, Fredrik J, et al.
(författare)
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Deregulated proliferation and differentiation in brain tumors
- 2015
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 359:1, s. 225-254
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Forskningsöversikt (refereegranskat)abstract
- Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment resistance, suppress tumor growth, and prevent recurrence in patients.
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| 503. |
- Swartling, Fredrik J., et al.
(författare)
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Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC
- 2012
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 21:5, s. 601-613
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Tidskriftsartikel (refereegranskat)abstract
- The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain. Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N-myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic Hedgehog (SHH) dependence and SHH independence, respectively. These differences were regulated in part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal.
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| 504. |
- Swartling, Fredrik J., 1975-, et al.
(författare)
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Signals that regulate the oncogenic fate of neural stem cells and progenitors
- 2014
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 260, s. 56-68
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Forskningsöversikt (refereegranskat)abstract
- Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors.
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| 505. |
- Sällström, Johan, et al.
(författare)
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Diabetes-induced hyperfiltration in adenosine A(1)-receptor deficient mice lacking the tubuloglomerular feedback mechanism
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 190:3, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Glomerular hyperfiltration is commonly found in diabetic patients early after the onset of disease. This is one of the first indications of the development of progressive diabetic nephropathy. It has been proposed that glomerular hyperfiltration is caused by decreased delivery of electrolytes to the macula densa due to the increased sodium and glucose reabsorption in the proximal tubule, which would increase the glomerular filtration rate (GFR) via the tubuloglomerular feedback (TGF) mechanism. In this study, we investigated the role of TGF in diabetes-induced glomerular hyperfiltration by inducing diabetes in adenosine A1-receptor knockout (A1AR−/−) mice known to lack a functional TGF mechanism. Methods: Diabetes was induced by alloxan (75 mg kg−1 bw) injected into the tail vein. The 24-hour urinary electrolyte excretion was measured in metabolic cages, the GFR determined by inulin clearance under isoflurane-anaesthesia, and histological changes evaluated. Results: All alloxan-treated animals developed hyperglycaemia (≥20 mm). Normoglycaemic animals had a similar GFR independent of genotype (A1AR+/+ 9.3 ± 0.5 vs. A1AR−/− 10.1 ± 0.8 μL min−1g−1 bw) and diabetes resulted in similar glomerular hyperfiltration in both groups (A1AR+/+ 14.0 ± 1.7, n = 9 vs. A1AR−/− 15.3 ± 1.9 μL min−1g−1 bw). Diabetic animals had a similar tendency to develop interstitial fibrosis, whereas the glomerular volume was similar in both genotypes, and unaltered by diabetes. Conclusions: This study shows that the A1AR−/− mice develop diabetes-induced glomerular hyperfiltration, demonstrating that the TGF mechanism is not the major cause of the development of hyperfiltration. Furthermore, the hyperfiltration in the present study was not related to alterations in the glomerular filtration area.
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| 506. |
- Sällström, Johan, et al.
(författare)
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Inhibition of sodium-linked glucose reabsorption in the kidney normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A1-receptor-deficient mice
- 2014
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 210:2, s. 440-445
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Tidskriftsartikel (refereegranskat)abstract
- Glomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. In this study, we investigated the role of the increased tubular sodium/glucose co-transport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback mechanism (TGF), we used adenosine A1-receptor deficient (A1AR-/-) mice known to lack a functional TGF mechanism, and compared the results to corresponding wild-type animals (A1AR+/+). Diabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose co-transporters were inhibited by phlorizin 30 minutes prior to GFR measurements. Normoglycemic animals had a similar GFR independent of genotype, and induction of diabetes resulted in similar glomerular hyperfiltration in both groups. Phlorizin had no effect on GFR in normoglycemic mice, whereas it reduced GFR in both genotypes during diabetes. Notably, the reduction was more pronounced in the A1AR-/-. This study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point.
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| 507. |
- Taxbro, Knut, et al.
(författare)
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Factors related to COVID-19 mortality among three Swedish intensive care units-A retrospective study
- 2023
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:6, s. 788-796
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Tidskriftsartikel (refereegranskat)abstract
- Background Mortality due to acute hypoxemic respiratory failure (AHRF) in patients with coronavirus disease-19 (COVID-19) differs across units, regions, and countries. These variations may be attributed to several factors, including comorbidities, acute physiological derangement, disease severity, treatment, ethnicity, healthcare system strain, and socioeconomic status. This study aimed to explore the features of patient characteristics, clinical management, and staffing that may be related to mortality among three intensive care units (ICUs) within the same hospital system in South Sweden.Methods We retrospectively analyzed ICU patients with COVID-19 and AHRF in Region Jonkoping County, Sweden. The primary outcome was the 90-day mortality rate. We used univariate and multivariable logistic regression analyses to investigate the relationship of predictors with outcomes.Results Between March 15, 2020, and May 31, 2021, 331 patients with AHRF and COVID-19 were admitted to the three ICUs. There were differences in disease severity, treatments, process-related factors, and socioeconomic factors between the units. These factors were related to 90-day mortality. After multivariable adjustment, age, severity of acute respiratory distress syndrome, and the number of nurses per ICU-bed independently predicted 90-day mortality.Conclusion Age, disease severity, and nurse staffing, but not treatment or socioeconomic status, were independently associated with 90-day mortality among critically ill patients with AHRF due to COVID-19. We also identified variations in care related processes, which may be a modifiable risk factor and warrants future investigation.
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| 508. |
- Taxbro, Knut, 1973-, et al.
(författare)
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Low mortality rates among critically ill adults with COVID-19 at three non-academic intensive care units in south Sweden
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:10, s. 1457-1465
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Tidskriftsartikel (refereegranskat)abstract
- Background The COVID-19 pandemic has put an exceptional strain on intensive care units worldwide. During the first year, the survival of patients with acute hypoxaemic respiratory failure appears to have improved. We aimed to describe the mortality rates, management characteristics and two pandemic waves during the first year at three non-academic rural intensive care units in Sweden. Methods We retrospectively analysed all cases of COVID-19 admitted to intensive care units in Region Jonkoping County during 1 year. The primary endpoint was 30-day mortality. Results Between 14th March 2020 and 13th March 2021, 264 patients were admitted to undergo intensive care with confirmed SARS-CoV-2 infection. The 30-day mortality rate after the initial intensive care admission was 12.9%, and this rate remained unchanged during both pandemic waves. However, we found several distinct differences between the two pandemic waves, including an increase in the use of high-flow nasal oxygen but a decrease in invasive mechanical ventilation use, biochemical markers of inflammation, continuous renal replacement therapy and length of stay in the intensive care unit. Conclusion Our study showed that critically ill patients with COVID-19 in Sweden have a low 30-day mortality rate which compares well with results published from academic centres and national cohorts throughout Scandinavia. During the second pandemic wave, the proportion of patients receiving invasive mechanical ventilation and continuous renal replacement therapy was lower than that in the first wave. This could be the result of increased knowledge and improved therapeutic options.
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| 509. |
- Tersmeden, Fredrik, et al.
(författare)
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350 näsor under 350 år
- 2018
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Bok (populärvet., debatt m.m.)abstract
- Lättsamt biografiskt översiktsverk med korta personbeskrivningar i ord och bild av dels de 190 personer som t o m 2017 införlivats i Akademiska Föreningens Nasotek, dels ytterligare 160 lundaanknutna historiska personer.
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| 510. |
- Thajudeen, Shamnath, et al.
(författare)
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Parametric modelling of steel connectors in a glulam-based post and beam building system - Towards a flexible product platform approach
- 2020
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Ingår i: Transdisciplinary Engineering for Complex Socio-technical Systems – Real-life Applications. - : IOS Press. - 9781643681115 - 9781643681108 ; , s. 564-573
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Konferensbidrag (refereegranskat)abstract
- House building projects are distinctive, and the degree of customisation creates bottlenecks in the design process and challenges for production, which results in longer lead time and higher costs. Aligned with a product platform approach, previous studies have introduced cost-effective approaches such as standardisation, modularization, configurators, etc. Still, components that cannot be completely modularized and configured due to high complexity level, may require a lot of engineering efforts during development. A platform approach that can be used to support engineer-to-order products that change over time still needs to be explored. The application of parametric modelling to automate the design process in the construction industry has the potential to further increase both the design and production efficiency. Thus, the objective of this research is to apply parametric modelling in the design of steel connectors used in a glulam based post and beam building system as part of a flexible product platform for increased design and production efficiency. A single case study has been carried out with a Swedish multi-storey house building company. Empirical data were gathered from a workshop with the design team followed by interviews, and document analysis. A computer-supported method for the steel bracket connectors has been developed, that connects post and beam components with pre-defined rules and constraints as part of the platform development. The result contributes to expanding knowledge about the development of a flexible product platform for improved design process and downstream production of customised components with parametric modelling support in the industrial post and beam buildng system.
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