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- Fernandes E Fernandes, José, et al.
(författare)
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The conundrum of asymptomatic carotid stenosis-determinants of decision and evidence
- 2020
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 8:19
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Forskningsöversikt (refereegranskat)abstract
- Management of asymptomatic carotid disease continues to challenge medical practice and present evidence is often conflicting. Stroke is a significant burden in Public Health and 11% to 15% appear as first neurologic event associated with asymptomatic carotid stenosis. Randomized trials provided support for Guidelines and Recommendations to intervene on asymptomatic stenosis, but at a known cost of a high number of unnecessary operations. Conflicting evidence from natural history studies and the widespread use of proper medical management including risk factors control, lowering-lipid drugs and strict control of arterial hypertension have reduced the incidence of strokes associated to asymptomatic carotid disease challenging established practice. Need to identify vulnerable lesions prone to develop thromboembolic brain events and also vulnerable patients at a higher risk of stroke is necessary and essential to further improve effectiveness of our interventions. After review of published literature on natural history of asymptomatic carotid stenosis, diagnostic methods to identify plaque vulnerability and present-day results of both endarterectomy and stenting, a strategy for management of asymptomatic carotid stenosis is suggested aiming to reduce unnecessary interventions and effectively contribute to stroke prevention.
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- Hasselgren, Kristina, et al.
(författare)
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Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease
- 2020
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.
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- Lu, Yingying, et al.
(författare)
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Telomere dysfunction promotes small vessel vasculitis via the LL37-NETs-dependent mechanism
- 2020
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Ingår i: Annals of Translational Medicine. - : AME PUBL CO. - 2305-5839 .- 2305-5847. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small vessel vasculitis (SVV) is a group of systemic autoimmune diseases that are mediated by neutrophil extracellular traps (NETs) in response to cathelicidin LL37, an aging molecular marker, which could be induced by telomere dysfunction. Therefore, in this study, we evaluated the hypothesis that telomere dysfunction in neutrophils may promote SVV via an LL37-NETs-dependent mechanism. Methods: We contrasted the release of neutrophil NETs from mice with telomere dysfunction, mice with DNA damage and wide-type mice. Neutrophil telomere length, the expression of LL37, and the formation of NETs were measured in SVV patients and healthy controls (HCs). The co-expression of gamma H2AX, LL37, and NETs were detected in SVV patients to evaluate the association of the immune aging of neutrophils and pro-inflammatory conditions. LL37 inhibitor was used to verify its key role in NETs release in SVV patients and DNA damage mice. Results: We found that NETs were over-induced by telomere dysfunction and DNA damage in mice, which may be associated with a marked increase in LL37. For patients with SVV, telomeres in neutrophils were significantly shortened, which was also associated with higher levels of LL37 and NETs. Inhibition of LL37 reduced the NETs released from neutrophils. Conclusions: Taken together, the results of these studies suggest that dysfunction of telomeres may promote SVV through the mechanism of LL37-dependent NETs. Thus, targeting the LL37-NETs may be a novel therapy for SVV.
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