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Sökning: WFRF:(Sandström Per A)

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1.
  • Korenblik, R., et al. (författare)
  • Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
  • 2022
  • Ingår i: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
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  • Östling, Jörgen, et al. (författare)
  • IL-17-high asthma with features of a psoriasis immunophenotype
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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  • Engstrand, J., et al. (författare)
  • Liver resection and ablation for squamous cell carcinoma liver metastases
  • 2021
  • Ingår i: BJS Open. - Oxford, United Kingdom : Oxford University Press. - 2474-9842. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS).METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS.RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30).CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.
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5.
  • Heil, J., et al. (författare)
  • Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis
  • 2021
  • Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168. ; 108:7, s. 834-842
  • Tidskriftsartikel (refereegranskat)abstract
    • Y Background: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. Methods: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. Results: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P=0.020) and resectability (90 versus 68 per cent; P=0.007). Major complications (26 versus 34 per cent; P=0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. Conclusion: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.
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  • Yaqub, S., et al. (författare)
  • Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial
  • 2021
  • Ingår i: Trials. - London, United Kingdom : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. Methods The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. Discussion The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness.
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  • Heil, Jan, et al. (författare)
  • Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection-A DRAGON collaborative analysis of 306 patients
  • 2022
  • Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 24:3, s. 413-421
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR >2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.
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  • Takala, S., et al. (författare)
  • Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers
  • 2023
  • Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 112:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.
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  • van Hilst, Jony, et al. (författare)
  • Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA)
  • 2019
  • Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 269:1, s. 10-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC).Background: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC.Methods: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival.Results: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60–400) vs 300 mL (150–500), P = 0.001] and hospital stay [8 (6–12) vs 9 (7–14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8–22) vs 22 (14–31), P< 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22–34] versus 31 (95% CI, 26–36) months (P = 0.929).Conclusions: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.
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  • Chand, Damini, 1986, et al. (författare)
  • Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.
  • 2013
  • Ingår i: Disease models & mechanisms. - Cambridge, UK : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 6:2, s. 373-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroblastoma is a childhood extracranial solid tumor which is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly required characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and 1464STOP) which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression we have employed cell culture based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position F1174I generates a gain-of-function receptor capable of activating intracellular targets, such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These are: (i) gain-of-function ligand independent mutations such as ALK(F1174), (ii) kinase-dead ALK mutants, e.g. ALK(I1250T)(Schonherr et al 2011a) or (iii) ALK mutations which are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (PF-02341066, Xalkori), albeit with differing levels of sensitivity.
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  • Fusai, Giuseppe Kito, et al. (författare)
  • Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries
  • 2023
  • Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).
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  • Hasselgren, Kristina, et al. (författare)
  • ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
  • 2021
  • Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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  • Hasselgren, Kristina, 1976- (författare)
  • Colorectal Liver Metastases – Different Aspects on Treatment with Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy and on Portal Vein Occlusion
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: For patients with colorectal liver metastases (CRLM), the only treatment with a possibility for long-term survival and cure is radical resection. The majority of patients are at the time of diagnosis not assessed as resectable because they have advanced disease in the liver or unresectable extrahepatic disease or are too frail to withstand liver surgery. Patients who at the time of diagnosis are not assessed as resectable may be treated with conversion chemotherapy to downsize the tumor burden and render the patient eligible for resection. One concern with chemotherapy administered preoperatively has been the potential negative effect on the future liver remnant (FLR), especially for patients with a low volume of the FLR who are undergoing techniques to increase the volume. Established techniques to increase the volume are portal vein occlusion (PVO) and two-staged hepatectomy (TSH). A more recent method is Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Due to the relative novelty of ALPPS, the long-term oncological results are not known. For patients with CRLM, resection of liver metastases is more favorable from a health economic perspective than palliative treatment and results in a higher quality of life than palliative chemotherapy. For patients undergoing ALPPS as well as TSH, the data are scarce. Aim: The aim of the first study was to determine whether preoperative chemotherapy has a negative impact on the volume increase for patients undergoing ALPPS. The aim of the second study was to analyze the temporal course of the volume increase in the FLR for patients undergoing PVO. The aim of the third study was to study the long-term outcome for patients randomized to ALPPS or TSH. The aim of the fourth study was to perform a health economic analysis of patients randomized to ALPPS or TSH. Methods: The first study was based on data from the ALPPS registry, which is an international registry initiated 2012. All patients included in the registry between 2012 and 2016 were included. The patients were divided into the following four groups: no preoperative chemotherapy, 1 regimen of neoadjuvant chemotherapy, more than 1 regimen, and more than 1 regimen with the addition of monoclonal antibodies. The volume increase between interventions 1 and 2 was analyzed. In the second study, a retrospective analysis was performed of patients randomized to TSH. Forty-eight patients were included. The volume increase of the FLR was analyzed as the kinetic growth rate (KGR). The KGR was calculated from PVO until radical hepatectomy or exclusion, as well as between the first and second radiological evaluations. In the third and fourth studies, patients randomized to ALPPS and TSH were included. In the third study, survival, as well as factors affecting the outcome, were analyzed. In the fourth study, a calculation of resource use was performed, as was an analysis of health-related quality of life (HRQoL) for the groups. Results: In the first study, it was found that chemotherapy had no negative impact on the volume increase for patients undergoing ALPPS. In the second study, it was found that the volume increase of the FLR was largest the first week after ALPPS. In the third study, it was found that patients randomized to ALPPS had a longer survival than those randomized to TSH. Of the factors affecting the outcome, resection of liver metastases had a significant impact. In the fourth study, no significant difference could be found in resource use or HRQoL for patients randomized to ALPPS over TSH. Conclusion: Patients with advanced CRLM undergoing ALPPS should receive preoperative chemotherapy, if indicated. For those undergoing PVO, early evaluation is crucial to evaluate the volume increase, and for those with insufficient increase, additional techniques to increase the volume should be considered. Resection of liver metastases is an important factor to improve the outcome. Further studies are warranted to conclude whether ALPPS or TSH is most effective from a health economic perspective.
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  • Hasselgren, Kristina, 1976-, et al. (författare)
  • Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO
  • 2019
  • Ingår i: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 23:3, s. 556-562
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPortal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.MethodsPatients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.ResultsForty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (4), compared to 1.5 (+/- 2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (+/- 4) the first week, compared to 4.3 (+/- 2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (+/- 2), respectively (+/- 0.1) (p=0.017).Discussion p id=Par4 The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.
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  • Hoshino, Ayuko, et al. (författare)
  • Tumour exosome integrins determine organotropic metastasis
  • 2015
  • Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 527:7578, s. 329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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22.
  • Hsiao, Ching-Lien, et al. (författare)
  • Nucleation and core-shell formation mechanism of self-induced InxAl1−xN core-shell nanorods grown on sapphire substrates by magnetron sputter epitaxy
  • 2016
  • Ingår i: Vacuum. - : Pergamon Press. - 0042-207X .- 1879-2715. ; 131, s. 39-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleation of self-induced nanorod and core-shell structure formation by surface-induced phase separation have been studied at the initial growth stage. The growth of well-separated core shell nanorods is only found in a transition temperature region (600 degrees C amp;lt;= T amp;lt;= 800 degrees C) in contrast to the result of thin film growth outside this region (T amp;lt; 600 degrees C or T amp;gt; 800 degrees C). Formation of multiple compositional domains, due to phase separation, after similar to 20 nm InxAl1-xN epilayer growth from sapphire substrate promotes the core-shell nanorod growth, showing a modified Stranski-Krastanov growth mode. The use of VN seed layer makes the initial growth of the nanorods directly at the substrate interface, revealing a Volmer-Weber growth mode. Different compositional domains are found on VN template surface to support that the phase separation takes place at the initial nucleation process and forms by a self-patterning effect. The nanorods were grown from In-rich domains and initiated the formation of core-shell nanorods due to spinodal decomposition of the InxAl1-xN alloy with a composition in the miscibility gap.
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23.
  • Lundgren, Linda, et al. (författare)
  • Management of incidental gallbladder cancer in a national cohort
  • 2019
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:9, s. 1216-1227
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. Methods: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007–2011 and 2012–2016) to evaluate changes over time. Results: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). Conclusion: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.
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24.
  • Lutgendorff, Femke, et al. (författare)
  • Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis.
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2, s. e4512-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P<0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P<0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.
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25.
  • Rosok, B. I, et al. (författare)
  • Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy in patients with colorectal liver-metastases and small future liver remnants; a translational substudy of the LIGRO-RCT
  • 2019
  • Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 21:8, s. 1017-1023
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Associated liver partition and portal vein ligation in staged hepatectomy (ALPPS) is an alternative resection method to portal vein embolization (PVE) in patients with small future liver remnants (FLR) but has been associated with early tumor recurrences. Methods: Twenty-four patients with colorectal liver metastases (CRLM) patients from the randomized multicenter LIGRO trial comparing outcome of ALPPS (n = 13) vs PVE (n = 11) were included in the study. Mutational analyses of the KRAS, NRAS, BRAF, PIC3CA and TP53 genes of the metastases were performed in 21 patients and correlated to early tumor recurrence. Results: Within 12 months, 13 patients experienced recurrences (6 in TSH group and 7 in ALPPS group). Nine of 13 patients with recurrences had mutations in the TP53 gene, while 3 of 8 patients without recurrence carried the same mutation. Only sporadic cases of the other mutations studied were identified. Conclusions: ALPPS did not appear to be associated with higher rate of rapid recurrences than PVE following radical resection of colorectal liver metastases. Mutations in genes associated with negative oncologic outcome after surgical resection most likely play a role for tumor recurrences in these patients.
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26.
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27.
  • Sandström, Per, et al. (författare)
  • ALPPS Improves Resectability Compared with Conventional Two-stage Hepatectomy in Patients with Advanced Colorectal Liver Metastasis : Results from a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial)
  • 2018
  • Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 267:5, s. 833-840
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome - RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
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28.
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29.
  • Tholander, Christopher, et al. (författare)
  • Ab initio calculations and experimental study of piezoelectric YxIn1-xN thin films deposited using reactive magnetron sputter epitaxy
  • 2016
  • Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 105, s. 199-206
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining theoretical prediction and experimental verification we investigate the piezoelectric properties of yttrium indium nitride (YxIn1-xN). Ab initio calculations show that the YxIn1-xN wurtzite phase is lowest in energy among relevant alloy structures for 0≤x≤0.5. Reactive magnetron sputter epitaxy was used to prepare thin films with Y content up to x=0.51. The composition dependence of the lattice parameters observed in the grown films is in agreement with that predicted by the theoretical calculations confirming the possibility to synthesize a wurtzite solid solution. An AlN buffer layer greatly improves the crystalline quality and surface morphology of subsequently grown YxIn1-xN films. The piezoelectric response in films with x=0.09 and x=0.14 is observed using piezoresponse force microscopy. Theoretical calculations of the piezoelectric properties predict YxIn1−xN to have comparable piezoelectric properties to ScxAl1-xN.
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30.
  • Amin, Awin, et al. (författare)
  • Patient-reported participation in hepatopancreatobiliary surgery cancer care : A pilot intervention study with patient-owned fast-track protocols
  • 2022
  • Ingår i: European Journal of Cancer Care. - : Wiley. - 0961-5423 .- 1365-2354. ; 31:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Fast-track concepts have been implemented in hepatopancreatobiliary surgery cancer care to improve postoperative recovery. For optimal postoperative care, patient participation is also required. The aim was to investigate and analyse whether an intervention with patient-owned fast-track protocols (PFTPs) may lead to increased patient participation and improve information for patients who underwent surgery for hepatopancreatobiliary cancer. Methods A quantitative comparative design with a control and intervention group was used. The participants in the intervention group followed a PFTP during their admission. After discharge, the patients answered a questionnaire regarding patient participation. Data analyses were performed with descriptive statistics and ANCOVA. Results The results are based on a total of 222 completed questionnaires: 116 in the control group and 106 in the intervention group. It is uncertain whether the PFTP increased patient participation and information, but its use may indicate an improvement for the patient group. Conclusion A successful implementation strategy for the use of PFTP, with daily reconciliations, could be part of the work required to improve overall satisfaction with patient participation.
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31.
  • Bergström, Christel A S, et al. (författare)
  • Hepatitis C virus NS3 protease inhibitors : large, flexible molecules of peptide origin show satisfactory permeability across Caco-2 cells
  • 2009
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 38:5, s. 556-563
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to investigate the intestinal absorption of tripeptide-based compounds intended for treatment of hepatitis C virus (HCV) infection. The intestinal permeability of 11 HCV NS3 protease inhibitors (Mw 687-841, ClogD(pH 7.4) 1.2-7.3 and 10-13 hydrogen bond donors/acceptors) was measured using Caco-2 cells. Each compound was investigated in the apical to basolateral (a-b) and basolateral to apical (b-a) direction at pH 7.4. For compounds displaying efflux the experiment was repeated in the presence of 1 microM GF120918 to investigate possible involvement of P-glycoprotein (Pgp; ABCB1). All compounds displayed intermediate to high permeability. Seven of them showed extensive efflux, with 31-114-fold higher permeability in the b-a direction than the a-b direction. Addition of the Pgp inhibitor GF120918 reduced the b-a transport rate for the effluxed compounds. However, for inhibitors with a C-terminal carboxylic acid and the acidic bioisosteres thereof the efflux was still significant. Hence, the negative charge resulted in efflux by other ABC-transporters than Pgp. From this study it can be concluded that small changes in the overall structure can lead to a large variation in permeability and efflux as shown by the inhibitors herein, properties that also may influence the resulting inhibition potency of the compounds when performing cell-based pharmacological assays.
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32.
  • Bergström, Göran, 1964, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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33.
  • Bergström, Göran, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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34.
  • Björnsson, Bergthor, et al. (författare)
  • Associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases - Intermediate oncological results
  • 2016
  • Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 42:4, s. 531-537
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two-stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. Material and methods: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. Results: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 nun (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. Conclusion: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH. (C) 2016 Elsevier Ltd. All rights reserved.
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35.
  • Björnsson, Bergthor, et al. (författare)
  • Segment 4 occlusion in portal vein embolization increase future liver remnant hypertrophy : A Scandinavian cohort study
  • 2020
  • Ingår i: International Journal of Surgery. - : ELSEVIER. - 1743-9191 .- 1743-9159. ; 75, s. 60-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The additional value of including segment 4 (S4) portal branches in right portal vein embolization (rPVE) is debated. The aim of the study was to explore this in a large multicenter cohort.Material and methods: A retrospective cohort study consisting of all patients subjected to rPVE from August 2012 to May 2017 at six Scandinavian university hospitals. PVE technique was essentially the same in all centers, except for the selection of main embolizing agent (particles or glue). All centers used coils or particles to embolize S4 branches. A subgroup analysis was performed after excluding patients with parts of or whole S4 included in the future liver remnant (FLR).Results: 232 patients were included in the study, of which 36 received embolization of the portal branches to S4 in addition to rPVE. The two groups (rPVE vs rPVE + S4) were similar (gender, age, co-morbidity, diagnosis, neoadjuvant chemotherapy, bilirubin levels prior to PVE and embolizing material), except for diabetes mellitus which was more frequent in the rPVE + S4 group (p = 0.02). Pre-PVE FLR was smaller in the S4 group (333 vs 380 ml, p = 0.01). rPVE + S4 resulted in a greater percentage increase of the FLR size compared to rPVE alone (47 vs 38%, p = 0.02). A subgroup analysis, excluding all patients with S4 included in the FLR, was done. There was no longer a difference in pre-PVE FLR between groups (333 vs 325 ml, p = 0.9), but still a greater percentage increase and also absolute increase of the FLR in the rPVE + S4 group (48 vs 38% and 155 vs 112 ml, p = 0.01 and 0.02).Conclusion: In this large multicenter cohort study, additional embolization of S4 did demonstrate superior growth of the FLR compared to standard right PVE.
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36.
  • Gnekow, Astrid K, et al. (författare)
  • A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - A final report.
  • 2017
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 81, s. 206-225
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.METHODS: Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology-Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02-7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.FINDINGS: No differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.INTERPRETATION: The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of 'duration of therapy' and 'age at stopping therapy'.
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37.
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38.
  • Hendrikx, Tijn, et al. (författare)
  • Atrial fibrillation among patients under investigation for suspected obstructive sleep apnea
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVES: Obstructive sleep apnea is common among patients with atrial fibrillation, but the prevalence and risk factors for atrial fibrillation among patients who are being investigated on suspicion of sleep apnea are not well known. The aim of the study was to estimate the prevalence of atrial fibrillation among patients investigated for suspected obstructive sleep apnea and to identify risk factors for atrial fibrillation among them.METHODS: The prevalence of atrial fibrillation was investigated among 201 patients referred for suspected obstructive sleep apnea. Patients without known atrial fibrillation were investigated with a standard 12-lead ECG at hospital and short intermittent handheld ECG recordings at home, during 14 days.RESULTS: Atrial fibrillation occurred in 13 of 201 subjects (6.5%), and in 12 of 61 men aged 60 years and older (20%). The prevalence of atrial fibrillation increased with sleep apnea severity (p = 0.038). All patients with atrial fibrillation were men and all had sleep apnea. Age 60 or older, the occurrence of central sleep apnea and diabetes mellitus were independent risk factors for atrial fibrillation after adjustments for body mass index, gender, sleep apnea and cardiovascular disease.CONCLUSIONS: Atrial fibrillation is common among subjects referred for sleep apnea investigation and the prevalence of atrial fibrillation increases with sleep apnea severity. Independent risk factors for atrial fibrillation among patients investigated for suspected obstructive sleep apnea include the occurrence of coexisting central sleep apnea, age 60 years or older and diabetes mellitus.
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39.
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40.
  • Henriksson, Martin, et al. (författare)
  • Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv
  • 2020
  • Ingår i: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 4:1, s. 109-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. Methods Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. Results A total of 3376 patients with HCC were registered over 8 years, 246 (7 center dot 3 per cent) of whom underwent transplantation. Some 501 (14 center dot 8 per cent) and 390 patients (11 center dot 6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14 center dot 1 per cent) and 426 patients (12 center dot 6 per cent) respectively; the remaining 1337 (39 center dot 6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4 center dot 6 (i.q.r. 2 center dot 0 to not reached) years after resection and 3 center dot 1 (2 center dot 3-6 center dot 7) years following ablation. In patients referred for palliative treatment, median survival was 1 center dot 4 (0 center dot 8-2 center dot 9), 0 center dot 5 (0 center dot 3-1 center dot 2) and 0 center dot 3 (0 center dot 1-1 center dot 0) years for the TACE, sorafenib and BSC groups respectively (P amp;lt; 0 center dot 001). Median survival was 0 center dot 9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1 center dot 4 years in 2013-2016 (P amp;lt; 0 center dot 001). Conclusion The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
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41.
  • Ibrahim, Farzana, et al. (författare)
  • 'I want to know why and need to be involved in my own care…' : a qualitative interview study with liver, bile duct or pancreatic cancer patients about their experiences with involvement in care.
  • 2019
  • Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 27:7, s. 2561-2567
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposePatients’ involvement in their own care is important for those with upper abdominal tumours. Care is often conducted according to standardized fast-track care programs (FTCP), and a shorter hospital stay is one of the goals. However, there is no research providing an in-depth perspective on patients’ experiences of involvement in care. In this qualitative study, we explored experiences of involvement among patients who had surgery for upper abdominal tumours and were cared for according to an FTCP.MethodsQualitative in-depth face-to-face interviews about patient involvement in care were conducted with 20 patients who had surgery for the liver, bile duct, or pancreatic cancer using an open-interview guide.ResultsThe most important findings are that customized information and active dialogue about care decisions stimulate patient involvement. We identified three themes from the analysed data: involvement depended on the quality of information, communication and involvement during the care period, and safety at discharge.ConclusionsIndividualized care and continuous information about treatment and care goals in the FTCP during the care process create trust between patients and healthcare professionals and increase patient experiences of involvement.
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42.
  • Johansen, Karin, et al. (författare)
  • High resection rate improves overall survival in elderly patients with pancreatic head cancer - A cohort study
  • 2021
  • Ingår i: International Journal of Surgery Open. - : Elsevier Science Ltd. - 2405-8572. ; 34
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is evidence that a high hospital volume of pancreaticoduodenectomy improves short-and long-term outcomes, but there are few population-based studies on the effect of a high resection rate in the population. The aim of this national, observational study was primarily to investigate differences in overall survival among elderly patients with cancer in the pancreatic head between high and low resection rate groups and secondarily to determine if counties with high resection rates of pancreaticoduodenectomy had more severe complications after surgery. Materials and methods: All patients in the Swedish National Registry for tumours in the pancreatic and periampullary region diagnosed between 2010 and 2018 with pancreatic head cancer were included in this retrospective cohort study. Patients were divided into low and high resection rate groups according to the yearly resection rates in the respective counties. For operative outcomes, all patients who had undergone pancreaticoduodenectomy were included regardless of diagnosis. The primary outcome of the study was overall survival among patients aged >= 70 years with pancreatic head cancer. Results: Among 13 933 patients in the registry, 7661 were 70 years or older, of whom 3006 had pancreatic head cancer. Overall survival was longer in high resection rate groups for patients aged >= 70 years, as for the age subgroups 70-79 years and >= 80 years (all p < 0.001). Among patients who had undergone pancreaticoduodenectomy aged >= 80 years the high resection rate counties showed an increased rate of severe complications, but no increase in 90-day mortality. Conclusion: High resection rate groups show a significantly longer overall survival among elderly patients with pancreatic head cancer in Sweden. This implies that there could be a survival benefit from increasing resections in low resection rate groups. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
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43.
  • Johansen, Karin, 1990-, et al. (författare)
  • There Is No Increase in Perioperative Mortality After Pancreaticoduodenectomy in Octogenarians : Results From the Swedish National Registry for Tumors in the Pancreatic and Periampullary Region
  • 2020
  • Ingår i: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 1:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this observational study was to compare postoperative mortality and complications between octogenarians and younger patients following pancreaticoduodenectomy (PD).Summary Background Data: With the growing elderly population and improved operative and postoperative results, PD is performed more frequently in octogenarians. Despite recent studies, it is uncertain whether elderly patients experience worse postoperative outcomes than younger patients.Methods: All patients registered in the Swedish National Registry for tumors in the pancreatic and periampullary region from 2010 to 2018 who underwent PD were included in the analysis.Results: Out of 13,936 patients included in the registry, 2793 patients underwent PD and were divided into the following age groups: <70 (n = 1508), 70–79 (n = 1137), and ≥80 (n = 148) years old. There was no significant difference in in-hospital, 30- or 90-day mortality among groups. The 2 older groups had a higher rate of medical and some surgical complications but not a significantly higher rate of complications ≥IIIa according to the Clavien-Dindo classification system. The 2 older groups had lower body mass index, higher American Society of Anesthesiologists and Eastern Cooperative Oncology Group scores, lower smoking rates, and a higher rate of preoperative biliary drainage than the <70-year-old group (all P < 0.001). The operation time was shorter in the oldest group.Conclusions: Despite the worse preoperative condition of octogenarians than younger patients, short-term mortality and serious complications were not increased. The shorter operation time, however, may indicate that patients in the oldest group were more strictly selected. With careful preoperative consideration, especially regarding cardiovascular morbidity, more octogenarians can potentially be safely offered PD.
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44.
  • Johansson, Stina M., et al. (författare)
  • A(1) receptor deficiency causes increased insulin and glucagon secretion in mice
  • 2007
  • Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 74:11, s. 1628-1635
  • Tidskriftsartikel (refereegranskat)abstract
    • Adenosine influences metabolism and the adenosine receptor antagonist caffeine decreases the risk of type 2 diabetes. In this study the metabolic role of one adenosine receptor subtype, the adenosine A(1)R, was evaluated in mice lacking this receptor [A(1)R (-/-)]. The HbA1c levels and body weight were not significantly different between wild type [A(1)R (+/+)] and A(1)R (-/-) mice (3-4 months) fed normal lab chow. At rest, plasma levels of glucose, insulin and glucagon were similar in both genotypes. Following glucose injection, glucose tolerance was not appreciably altered in A(1)R (-/-) mice. Glucose injection induced sustained increases in plasma insulin and glucagon levels in A(1)R (-/-) mice, whereas A(1)R (+/+) control mice reacted with the expected transient increase in insulin and decrease in glucagon levels. Pancreas perfusion experiments showed that A(1)R (-/-) mice had a slightly higher basal insulin secretion than A(1)R (+/+) mice. The first phase insulin secretion (initiated with 16.7 mM glucose) was of the same magnitude in both genotypes, but the second phase was significantly enhanced in the A(1)R (-/-) pancreata compared with A(1)R (+/+). Insulin- and contraction-mediated glucose uptake in skeletal muscle were not significantly different between in A(1)R (-/-) and A(1)R (+/+) mice. All adenosine receptors were expressed at mRNA level in skeletal muscle in A(1)R (+/+) mice and the mRNA A(2A)R, A(2B)R and A(3)R levels were similar in A(1)R (-/-) and A(1)R (+/+) mice. In conclusion, the A(1)R minimally affects muscle glucose uptake, but is important in regulating pancreatic islet function.
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45.
  • Korrel, Maarten, et al. (författare)
  • Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials
  • 2021
  • Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 23:3, s. 323-330
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Minimally invasive distal pancreatectomy (MIDP) has been suggested to reduce postoperative outcomes as compared to open distal pancreatectomy (ODP). Recently, the first randomized controlled trials (RCTs) comparing MIDP to ODP were published. This individual patient data meta analysis compared outcomes after MIDP versus ODP combining data from both RCTs. Methods: A systematic literature search was performed to identify RCTs on MIDP vs. ODP, and individual patient data were harmonized. Primary endpoint was the rate of major (Clavien-Dindo > III) complications. Sensitivity analyses were performed in high-risk subgroups. Results: A total of 166 patients from the LEOPARD and LAPOP RCTs were included. The rate of major complications was 21% after MIDP vs. 35% after ODP (adjusted odds ratio 0.54; p = 0.148). MIDP significantly reduced length of hospital stay (6 vs. 8 days, p = 0.036), and delayed gastric emptying (4% vs. 16%, p = 0.049), as compared to ODP. A trend towards higher rates of postoperative pancreatic fistula was observed after MIDP (36% vs. 28%, p = 0.067). Outcomes were comparable in high-risk subgroups. Conclusion: This individual patient data meta-analysis showed that MIDP, when performed by trained surgeons, may be regarded as the preferred approach for distal pancreatectomy. Outcomes are improved after MIDP as compared to ODP, without obvious downsides in high-risk subgroups.
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46.
  • Lang, Hauke, et al. (författare)
  • 10th Anniversary of ALPPS-Lessons Learned and quo Vadis
  • 2019
  • Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 269:1, s. 114-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been tested in various indications and clinical scenarios, leading to steady improvements in safety. This report presents the current status of ALPPS. Summary Background Data: ALPPS offers improved resectability, but drawbacks are regularly pointed out regarding safety and oncologic benefits. Methods: During the 12th biennial congress of the European African-Hepato-Pancreato-Biliary Association (Mainz, Germany, May 23-26, 2017) an expert meeting "10th anniversary of ALPP" was held to discuss indications, management, mechanisms of regeneration, as well as pitfalls of this novel technique. The aim of the meeting was to make an inventory of what has been achieved and what remains unclear in ALPPS. Results: Precise knowledge of liver anatomy and its variations is paramount for success in ALPPS. Technical modifications, mainly less invasive approaches like partial, mini- or laparoscopic ALPPS, mostly aiming at minimizing the extensiveness of the first-stage procedure, are associated with improved safety. In fibrotic/cirrhotic livers the degree of future liver remnant hypertrophy after ALPPS appears some less than that in noncirrhotic. Recent data from the only prospective randomized controlled trial confirmed significant higher resection rates in ALPPS with similar peri-operative morbidity and mortality rates compared with conventional 2-stage hepatectomy including portal vein embolization. ALPPS is effective reliably even after failure of portal vein embolization. Conclusions: Although ALPPS is now an established 2-stage hepatectomy additional data are warranted to further refine indication and technical aspects. Long-term oncological outcome results are needed to establish the place of ALPPS in patients with initially nonresectable liver tumors.
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47.
  • Larnebratt, Anton, et al. (författare)
  • Information is the key to successful participation for patients receiving surgery for upper gastrointestinal cancer
  • 2019
  • Ingår i: European Journal of Cancer Care. - : John Wiley & Sons. - 0961-5423 .- 1365-2354. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • Fast-track programmes are aimed at improving perioperative care. The purpose of this study was to identify and explore patient participation among patients who had surgery for liver, bile duct or pancreatic cancer and followed a fast-track programme. A total of 116 questionnaires to investigate patient participation were analysed. Information was important for the patients, as was having the opportunity to ask questions and express personal views. The results showed differences by sex; men responded to a greater extent that they did not want to make decisions as a patient (p = 0.044) and that they had been motivated to take more responsibility for their future health (p = 0.011). Patients with pancreatic cancer discussed treatment goals with doctors to a greater extent than did patients with liver cancer (p = 0.041). Half of the patients perceived that they had not been involved in their care planning after discharge but had a desired to be involved. This seems to be an important point to improve in future care, and also that professionals should be aware of patients' needs for information and participation, especially at discharge.
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48.
  • Lundgren, Linda, 1973- (författare)
  • Incidental Gallbladder Cancer : Incidence, predictors, management and outcome in a Swedish population
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Cholecystectomy is a common surgical procedure and incidental gallbladder cancer is a rare and unexpected finding at a cholecystectomy performed upon benign indications. Whether to perform routine or selective histopathology of the gallbladder specimen is still a subject for discussion. The prognosis of gallbladder cancer is largely affected by tumour stage and treatment.Aims: The overall aim was to study whether routine histological examination of the gallbladder specimen is of clinical and health economic value; determine if there are any predictive factors of incidental gallbladder cancer at benign cholecystectomy and compare the management and outcome of incidental gallbladder cancer patients in Sweden.Methods: All studies were based on registry data from GallRiks (The Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography) between 2007 and 2016, with some modifications between studies. Complemental cross-linkage was made to national registries, and medical records were reviewed. Papers I, II and III were population-based observational studies with prospectively and retrospectively collected data. Paper IV was a health economic evaluation based on the results from papers I and III.Results and conclusions: Hospitals submitting >75 per cent of gallbladder specimens diagnosed a higher proportion of incidental gallbladder cancer than did hospitals submitting ≤25 per cent of samples (paper I). Incidental gallbladder cancer was more prevalent in older patients, women and patients with acute or previous cholecystitis, as well as ongoing jaundice. The risk model based on predictive preoperative factors was further improved by adding a macroscopic assessment of the gallbladder (paper II). Predictive factors for gallbladder cancer appeared to have an impact on which specimens were submitted in hospitals with a selective approach of histopathology (paper I). For pT2 and pT3 patients, re-resection improved diseasespecific survival, although these groups differed in terms of age and comorbidity (paper III). Residual disease was an independent factor for impaired survival. A change to routine histopathology of gallbladder specimens in Sweden would lead to increased costs with little improved health outcomes. Instead, a more standardized approach to selective histology would be needed (paper IV).
  •  
49.
  • Lutgendorff, Femke, 1981-, et al. (författare)
  • Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis
  • 2008
  • Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 μg·kg-1·h-1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-κB activation. The severity of pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5, P = 0.014). AP-induced NF-κB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD 450nm/mg nuclear protein, P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein, P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 μmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 μmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress. Copyright © 2008 the American Physiological Society.
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50.
  • Mosomtai, G., et al. (författare)
  • Characterizing movement patterns of nomadic pastoralists and their exposure to rift valley fever in Kenya
  • 2023
  • Ingår i: The international archives of the photogrammetry, remote sensing and spatial information sciences. - : Copernicus GmbH. - 1682-1750 .- 2194-9034. ; , s. 211-216
  • Konferensbidrag (refereegranskat)abstract
    • The role of animal movement in spreading infectious diseases is highly recognized by various legislations and institutions such as the World Organisation for Animal Health and the International Animal Health Code. The increased interactions at the nexus of human-animal-ecosystem interface have seen an unprecedented introduction and reintroduction of new zoonotic diseases with high socio-economic impacts such as the COVID-19 pandemic. Rift Valley fever (RVF) is a zoonotic disease that affects both humans and animals and is transmitted by Aedes mosquitoes or through contact with the body fluids of infected animals. This study seeks to characterize movement patterns of pastoralist and how this movement behaviour increases their susceptibility to RVF virus exposure. We levarage on a rapidly growing field of movement ecology to monitor five herds collared from 2013 - 2015 in an RVF endemic semi-arid region in Kenya. The herds were also sampled for RVF antibodies to assess their exposure to RVF virus during the rainy seasons. adehabitatLT package in R was used to analyze the trajectory data whereas the first passage time (FPT) analysis was used to measure the area utilized in grazing. Sedentary herds grazed within 15km radius while migrating herds presented restricted space use patterns during the dry seasons and transient movement during the start and end of the rainy season. Furthermore, RVF virus antibodies were generally low for sedentary herds whereas the migrating herds recorded high levels during their transition periods. This study can be used to identify RVF risk zones for timely and targeted management strategies.
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