| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 4. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 5. |
- Wray, Selina, et al.
(författare)
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Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
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| 6. |
- Jandrić, Petar, et al.
(författare)
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Teaching in the Age of Covid-19
- 2020
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Ingår i: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-4868 .- 2524-485X. ; 2:3, s. 1069-1230
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A collection of 84 author's testimonies and workspace photographs between 18 March and 5 May 2020.
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| 7. |
- Jandrić, Petar, et al.
(författare)
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Teaching in the Age of Covid-19—1 Year Later
- 2021
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Ingår i: Postdigital Science and Education. - : Springer. - 2524-485X .- 2524-4868. ; 3:3, s. 1073-1223
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Holmqvist, Staffan, et al.
(författare)
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Generation of human pluripotent stem cell reporter lines for the isolation of and reporting on astrocytes generated from ventral midbrain and ventral spinal cord neural progenitors.
- 2015
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Ingår i: Stem Cell Research. - : Elsevier BV. - 1876-7753 .- 1873-5061. ; 15:1, s. 203-220
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes play a critical role during the development and the maintenance of the CNS in health and disease. Yet, their lack of accessibility from fetuses and from the brain of diseased patients has hindered our understanding of their full implication in developmental and pathogenic processes. Human pluripotent stem cells (PSCs) are an alternative source to obtain large quantities of astrocytes in vitro, for mechanistic studies of development and disease. However, these studies often require highly pure populations of astrocytes, which are not always achieved, depending on the PSC lines and protocols used. Here, we describe the generation and characterization of human PSC reporter lines expressing TagRFP driven by the ABC1D region of the human GFAP promoter, as new cellular model for generating homogenous population of astrocytes generated from CNS regionally defined PSC-derived neural progenitors. GFAABC1D::TagRFP-expressing astrocytes can be purified by fluorescent-activated cell sorting and maintain a bright expression for several additional weeks. These express canonical astrocyte markers NF1A, S100β, CX43, GLAST, GS and CD44. These new cellular models, from which highly pure populations of fluorescence-expressing astrocytes can be obtained, provide a new platform for studies where pure or fluorescently labeled astrocyte populations are necessary, for example to assess pro-inflammatory cytokine and chemokine release in response to specific treatment, and uptake and degradation of fluorescently labeled pathogenic proteins, as reported in this study.
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| 9. |
- Horrocks, Mathew Harry, et al.
(författare)
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Single-molecule imaging of individual amyloid protein aggregates in human biofluids.
- 2016
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Ingår i: ACS chemical neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 16;7:3, s. 399-406
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Tidskriftsartikel (refereegranskat)abstract
- The misfolding and aggregation of proteins into amyloid fibrils characterizes many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We report here a method, termed SAVE (single aggregate visualization by enhancement) imaging, for the ultra-sensitive detection of individual amyloid fibrils and oligomers using single-molecule fluorescence microscopy. We demonstrate that this method is able to detect the presence of amyloid aggregates of alpha-synuclein, tau and amyloid-β. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a two-fold increase in the average aggregate concentration in CSF from PD patients compared to age-matched controls. Taken together, we conclude that this method provides an opportunity to characterize the structural nature of amyloid aggregates in a key biofluid, and therefore has the potential to study disease progression in both animal models and humans to enhance our understanding of neurodegenerative disorders.
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| 10. |
- Reyes, Juan F, et al.
(författare)
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A cell culture model for monitoring α-synuclein cell-to-cell transfer.
- 2015
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 77:Jul 16, s. 266-275
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Tidskriftsartikel (refereegranskat)abstract
- The transfer of α-synuclein (α-syn) between cells has been proposed to be the primary mechanism of disease spreading in Parkinson's disease. Several cellular models exist that monitor the uptake of recombinant α-syn from the culture medium. Here we established a more physiologically relevant model system in which α-syn is produced and transferred between mammalian neurons. We generated cell lines expressing either α-syn tagged with fluorescent proteins or fluorescent tags alone then we co-cultured these cell lines to measure protein uptake. We used live-cell imaging to demonstrate intercellular α-syn transfer and used flow cytometry and high content analysis to quantify the transfer. We then successfully inhibited intercellular protein transfer genetically by down-regulating dynamin or pharmacologically using dynasore or heparin. In addition, we differentiated human induced pluripotent stem cells carrying a triplication of the α-syn gene into dopaminergic neurons. These cells secreted high levels of α-syn, which was taken up by neighboring neurons. Collectively, our co-culture systems provide simple but physiologically relevant tools for the identification of genetic modifiers or small molecules that inhibit α-syn cell-to-cell transfer.
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| 11. |
- Ustun, Celalettin, et al.
(författare)
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Hematopoietic stem-cell transplantation for advanced systemic mastocytosis
- 2014
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:29, s. 3264-3274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
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| 12. |
- Vynnycky, Michael, et al.
(författare)
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On the formation of fold-type oscillation marks in the continuous casting of steel
- 2017
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Ingår i: Royal Society Open Science. - : Royal Society. - 2054-5703. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Asymptotic methods are employed to revisit an earlier model for oscillation-mark formation in the continuous casting of steel. A systematic non-dimensionalization of the governing equations, which was not carried out previously, leads to a model with 12 dimensionless parameters. Analysis is provided in the same parameter regime as for the earlier model, and surprisingly simple analytical solutions are found for the oscillation-mark profiles; these are found to agree reasonably well with the numerical solution in the earlier model and very well with fold-type oscillation marks that have been obtained in more recent experimental work. The benefits of this approach, when compared with time-consuming numerical simulations, are discussed in the context of auxiliary models for macrosegregation and thermomechanical stresses and strains.
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