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| 2. |
- Augustinus, Simone, et al.
(författare)
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Ideal Outcome After Pancreatoduodenectomy : A Transatlantic Evaluation of a Harmonized Composite Outcome Measure
- 2023
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Ingår i: Annals of Surgery. - 0003-4932. ; 278:5, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden. Background: Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO). Methods: This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications - Clavien-Dindo ≥3, (3) postoperative pancreatic fistula - International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay >75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models. Results: Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P<0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO. Conclusions: The newly developed composite outcome measure "Ideal Outcome"can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.
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| 3. |
- Courseaux, A, et al.
(författare)
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Definition of the minimal MEN 1 candidate area based on a 5-Mb integrated map proximal to 11q13 : The european consortium on men1
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 37:3, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
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| 4. |
- Davis, Catherine H., et al.
(författare)
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Impact of Neoadjuvant Therapy for Pancreatic Cancer : Transatlantic Trend and Postoperative Outcomes Analysis
- 2024
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Ingår i: Journal of the American College of Surgeons. - : LIPPINCOTT WILLIAMS & WILKINS. - 1879-1190 .- 1072-7515. ; 238:4, s. 613-621
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and short-term outcomes in patients with PDAC undergoing pancreatoduodenectomy (PD) among registries from the US and Canada, Germany, the Netherlands, and Sweden. STUDY DESIGN: Databases from 2 multicenter (voluntary) and 2 nationwide (mandatory) registries were queried from 2018 to 2020. Patients undergoing PD for PDAC were compared based on the use of upfront surgery vs NAT. Adoption of NAT was measured in each country over time. Thirty-day outcomes, including the composite measure (ideal outcomes), were compared by multivariable analyses. Sensitivity analyses of patients undergoing vascular resection were performed. RESULTS: Overall, 11,402 patients underwent PD for PDAC with 33.7% of patients receiving NAT. The use of NAT increased steadily from 28.3% in 2018 to 38.5% in 2020 (p < 0.0001). However, use of NAT varied widely by country: the US (46.8%), the Netherlands (44.9%), Sweden (11.0%), and Germany (7.8%). On multivariable analysis, NAT was significantly (p < 0.01) associated with reduced rates of serious morbidity, clinically relevant pancreatic fistulae, reoperations, and increased ideal outcomes. These associations remained on sensitivity analysis of patients undergoing vascular resection. CONCLUSIONS: NAT before PD for pancreatic cancer varied widely among 4 Western audits yet increased by 26% during 3 years. NAT was associated with improved short-term outcomes.
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| 5. |
- Latenstein, Anouk E.J., et al.
(författare)
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The use and clinical outcome of total pancreatectomy in the United States, Germany, the Netherlands, and Sweden
- 2021
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Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 170:2, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total pancreatectomy has high morbidity and mortality and differences among countries are currently unknown. This study compared the use and postoperative outcomes of total pancreatectomy among 4 Western countries. Methods: Patients who underwent one-stage total pancreatectomy were included from registries in the United States, Germany, the Netherlands, and Sweden (2014–2018). Use of total pancreatectomy was assessed by calculating the ratio total pancreatectomy to pancreatoduodenectomy. Primary outcomes were major morbidity (Clavien Dindo ≥3) and in-hospital mortality. Predictors for the primary outcomes were assessed in multivariable logistic regression analyses. Sensitivity analysis assessed the impact of volume (low-volume <40 or high-volume ≥40 pancreatoduodenectomies annually; data available for the Netherlands and Germany). Results: In total, 1,579 patients underwent one-stage total pancreatectomy. The relative use of total pancreatectomy to pancreatoduodenectomy varied up to fivefold (United States 0.03, Germany 0.15, the Netherlands 0.03, and Sweden 0.15; P <.001). Both the indication and several baseline characteristics differed significantly among countries. Major morbidity occurred in 423 patients (26.8%) and differed (22.3%, 34.9%, 38.3%, and 15.9%, respectively; P <.001). In-hospital mortality occurred in 85 patients (5.4%) and also differed (1.8%, 10.2%, 10.8%, 1.9%, respectively; P <.001). Country, age ≥75, and vascular resection were predictors for in-hospital mortality. In-hospital mortality was lower in high-volume centers in the Netherlands (4.9% vs 23.1%; P =.002), but not in Germany (9.8% vs 10.6%; P =.733). Conclusion: Considerable differences in the use of total pancreatectomy, patient characteristics, and postoperative outcome were noted among 4 Western countries with better outcomes in the United States and Sweden. These large, yet unexplained, differences require further research to ultimately improve patient outcome.
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| 6. |
- Musi, N., et al.
(författare)
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Metformin increases AMP-activated-protein-kinase activity in skeletal of subjects with type 2 diabetes
- 2002
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Ingår i: Diabetes. - Alexandra, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 51:7, s. 2074-2081
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Tidskriftsartikel (refereegranskat)abstract
- Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK α2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK α2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK α2.
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| 7. |
- Williamsson, C., et al.
(författare)
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Sustainability of an Enhanced Recovery Program for Pancreaticoduodenectomy with Pancreaticogastrostomy
- 2019
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 108:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enhanced recovery program for pancreaticoduodenectomy have become standard care. Little is known about adherence rates and sustainability of the program, especially when pancreaticogastrostomy is used in reconstruction. The aim of this study was, therefore, to evaluate adherence rates and continued outcome, after implementation of an enhanced recovery program. Methods: Consecutive patients undergoing pancreaticoduodenectomy at the Department of Surgery, Skåne University Hospital, Lund, Sweden were followed, after implementation of enhanced recovery program, October 2012. In April 2015, some items in the enhanced recovery program were modified, namely earlier removal of nasogastric tubes and abdominal drain. The patients were analyzed in three groups, the implementation group (control) and two post-implementation groups; intermediate and modified group. Sustainability was assessed according to length of stay and adherence rate. Results: In total, 160 patients were identified. The overall protocol adherence rate increased from 65% to 72%, p = 0.035. While the pre- and intraoperative protocol items were fulfilled to more than >90%, the postoperative were lower, but increasing over time; 48%, 50%, and 58%, p = 0.033. Postoperative complications and hospital length of stay did not change significantly. Conclusion: The positive outcome of an enhanced recovery program for pancreaticoduodenectomy was reasonably well sustained. Compliance with the protocol has increased, but strict adherence remains a challenge, especially with the postoperative items.
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| 8. |
- Williamsson, D., et al.
(författare)
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An Approach to Integrated Modularization
- 2016
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Ingår i: Procedia CIRP. - : Elsevier. - 2212-8271. ; , s. 613-617
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Konferensbidrag (refereegranskat)abstract
- A modular architecture is a strategic means to deliver external variety (to the customers) and internal commonality (to the manufacturing organization). A common view is that a module should be a physical and functional building block, with well-defined and standardized interfaces between modules, and that it should be chosen for company specific reasons. Existing methodologies, such as Modular Function Deployment with the Modular Indication Matrix (MIM) representation of identified company-specific module drivers, can be used to assist the task to identify modules. Other approaches, such as clustering of the Design Structure Matrix product representation, may be used to identify modules from a technical complexity point of view. A new methodology for product modularization that integrates technical complexity and company strategies is proposed in this paper. The core of the presented methodology is to adapt the component-DSM with MIM-strategies, before clustering this hybrid representation with the previously presented IGTA++ clustering algorithm. The proposed methodology is exemplified and logically verified with an industrial test rig modularization case. The modular test rig architecture chosen with the new methodology is shown to have 53% less complexity, as defined by Pugh, compared with the original architecture, and it could potentially reduce the risk of design mistakes, and reduce the development time by up to 70%. It is also estimated that it would be possible to reuse up to 57% of the modules, in future test rig redesign projects, which indicates potentially large savings in cost and development time.
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| 9. |
- Williamsson, D., et al.
(författare)
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Product architecture transition in a modular cyber-physical truck
- 2019
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Ingår i: Journal of Computing and Information Science in Engineering. - : American Society of Mechanical Engineers (ASME). - 1530-9827 .- 1944-7078. ; 19:3
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Tidskriftsartikel (refereegranskat)abstract
- A modular product architecture is a strategic means to deliver external variety and internal commonality. In this paper, we propose a new clustering-based method for product modularization that integrates product complexity and company business strategies. The proposed method is logically verified by a studied industrial case, where the architecture of a heavy truck driveline is analyzed in terms of how it has evolved over a couple of decades, due to changed business strategies and the evolution of new technology. The presented case indicates that the new methodology is capable of identifying and proposing reasonable module candidates that address product complexity as well as company-specific strategies. Furthermore, the case study clearly shows that the business strategic reasons for a specific architecture can be found by analyzing how sensitive the clusters are to changes in the module drivers (MD).
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