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- Beziat, Vivien, et al.
(author)
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NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs
- 2013
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:14, s. 2678-2688
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Journal article (peer-reviewed)abstract
- Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.
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| 3. |
- Hehlmann, Ruediger, et al.
(author)
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The European LeukemiaNet : achievements and perspectives
- 2011
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:1, s. 156-162
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Journal article (peer-reviewed)abstract
- The only way to cure leukemia is by cooperative research. To optimize research, the European Leukemia Net integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European Leukemia Net has steadily expanded and has unified leukemia research across Europe. The European Leukemia Net grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European Leukemia Net has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European Leukemia Net-Foundation) will take over when the support of the European Commission ends.
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| 4. |
- Ljungman, David, et al.
(author)
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Cost-Utility Estimation of Surgical Treatment of Pancreatic Carcinoma Aimed at Cure.
- 2011
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In: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 35:3, s. 662-70
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Journal article (peer-reviewed)abstract
- BACKGROUND: Little is reported on costs for radical tumor resections of pancreatic carcinoma in relationship to adjusted quality of life survival postoperatively. Therefore, the aim of the present study was to estimate the cost utility of surgical treatment aimed at cure. METHODS: A population-based cohort of patients with exocrine or ampullary pancreatic adenocarcinoma resected for cure in Gothenburg University Hospitals during 1998-2005 were evaluated retrospectively (n=139). Total inpatient and outpatient healthcare costs were available for 103 patients, and health-related quality of life (HRQL) (based on the SF-36 Health Survey) were assessed preoperatively and postoperataively in 119 patients. Survival and utility index (SF-36-6D) across 5years of postoperative follow-up were used to achieve quality adjusted life years. RESULTS: Mean survival after resection was 977days for patients with exocrine pancreatic carcinoma, with expected differences among subgroups as related to disease stage (p<0.01), in agreement with international reports. The HRQL index was 0.65±0.06 preoperatively, 0.63±0.04 early postoperatively (<1year) and 0.69±0.06 at long-term follow-up (1-5years) compared to 0.77±0.02 in age-matched healthy reference individuals from the Swedish population (p<0.05). Total lifetime costs for treatments including surgery and adjuvant chemotherapy were 39,000 per patient, with a mean of 1.13 (95% Confidence Interval [CI] 0.93-1.40) QALYs across 5years follow-up. The cost per QALY was 35,000 (95% CI 28,026-41,947). CONCLUSIONS: Resection aimed at cure of pancreatic exocrine ductal carcinoma provided costs for one quality adjusted year of survival comparable to other complex surgical treatments within cost limits regarded as reasonable to bear by the Swedish health care system, as well as in several other Western countries.
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| 5. |
- Ljungman, David, et al.
(author)
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Cost-Utility Estimations of Palliative Care in Patients With Pancreatic Adenocarcinoma: A Retrospective Analysis.
- 2013
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In: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 37:8, s. 1883-1891
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Journal article (peer-reviewed)abstract
- BACKGROUND: We earlier reported cost-utility estimates in patients who undergo resection aimed at cure for pancreatic carcinoma. The present study describes similar information on patients with unresectable tumors who experienced palliative care only. METHODS: A population-based cohort of patients with exocrine pancreatic adenocarcinoma during 1998-2005 was evaluated retrospectively (n=444). Total direct health care costs at departments of surgery and oncology, for primary health care, and at hospice were achieved. Self-estimated health-related quality of life (HRQL) was assessed by the SF-36. A single preference-based utility index, SF-6D, was derived from SF-36 items to estimate quality-adjusted life years (QALYs). Results were compared to similar findings in a previously reported group of patients with pancreatic carcinoma resected for cure (n=31). RESULTS: Palliative care patients (n=305) had impaired HRQL particularly related to physical domains. The mean preference-based health utility index at diagnosis was 0.65±0.02 [95% confidence interval (CI) 0.61-0.69] compared to 0.77±0.02 (95% CI 0.75-0.79) in healthy reference individuals. Total direct health care costs were 50% in patients on palliative care compared to costs for surgical R0 resections (23,701 and 50,950, respectively). QALYs for 1year from diagnosis were 0.2 (95% CI 0.17-0.23) in patients on palliative care and 0.48 (95% CI 0.44-0.54) in resection patients. Costs per QALY were 118,418 and 106,146, respectively (95% CI 103,048-139,418 and 94,352-115,795). CONCLUSIONS: Optimized palliative care of patients with exocrine pancreatic carcinoma had costs per achieved utility similar to those for surgical resections aimed at cure.
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| 6. |
- Ljungman, David
(author)
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Pancreatic Cancer. Experimental and Clinical Studies
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Background: Pancreatic cancer is one of the most lethal of known cancers and the only treatment with possibility of cure is surgery. The costs associated with treatment of pancreatic cancer are reputably high, both in terms of morbidity and financially. To reinforce decision making there is a need to assess the costs and benefits of current treatment. Furthermore, the incitements to develop therapeutic alternatives and biologically characterize individual tumors are considerable. Methods: Evaluation of effects of proteasome inhibition on intracellular signaling systems using in vitro and in vivo experiments. Estimation of achieved utilities and direct healthcare costs based on a clinical cohort. Assessment of prognostic significance of structural genomic aberrations using comparative genomic hybridization and single nucleotide polymorphism analysis on resected tumor tissue. Results: Proteasome inhibition activated an antiapoptotic and mitogenic therapy resistance response in several mediators (EGFR, JNK, ERK and PI3K/Akt) and the inhibition of Akt and JNK increased the tumoricidal effect of proteasome inhibitors. The activation was EGFR independent and the increased cell death was not NF-κB mediated. Patients undergoing resections with curative aim and patients receiving palliative care both experienced decreased health related quality of life in all SF-36 dimensions at diagnosis, without apparent improvement over time. The cost of treatment for patients undergoing surgery was two times the cost for the palliative patients (€50,950 vs. €23,701). Interestingly, already after one year the achieved QALY was twice as large in the resection group (0.48 vs. 0.20) resulting in cost per QALY neutralization between groups. DNA copy number alterations were seen in 2p11.2, 3q24, 8p11.22, 14q11.2 and 22q11.21. No convincing specific aberrations of prognostic value were found. Short survival was however responsible for 67% of total copy number variation and associated with significantly more amplifications, possibly related to alterations in chromosome 2, 11 and 21. Conclusions: Proteasome inhibition is a promising adjunct in horizontal targeted therapy regimens and the effect may be potentiated by simultaneous inhibition of signaling systems. Costs for pancreatic cancer surgery are comparable to other major healthcare interventions and long term survival in a few is effectively increasing cost-effectiveness on patient group basis. DNA from patients with poor prognosis contains more amplifications and seems to be generally more degenerated possibly indicating a greater genomic instability. The pancreatic cancer mutational profile is displaying vast inter-individual heterogeneity and most mutations are probably passengers.
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| 7. |
- Lundgren, Fredrik, et al.
(author)
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PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
- 2010
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
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Journal article (peer-reviewed)abstract
- BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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