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- Aguiar, A., et al.
(författare)
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Practices in prescribing protein substitutes for PKU in Europe : No uniformity of approach
- 2015
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192 .- 1096-7206. ; 115:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: There appears little consensus concerning protein requirements in phenylketonuria (PKU). Methods: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. Results: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants <1 year, >2-3 g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n = 4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). Conclusions: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.
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- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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- Beziat, Vivien, et al.
(författare)
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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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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:14, s. 2678-2688
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Tidskriftsartikel (refereegranskat)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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- Grip, L, et al.
(författare)
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Coronary angioplasty in patients with unstable angina, with special reference to preceding treatment with antithrombin III and heparin
- 1996
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Ingår i: CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 2:2, s. 107-115
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Seventy-nine patients undergoing percutane ous transluminal coronary angioplasty (PTCA) for unsta ble angina were analyzed with respect to preceding an tithrombin treatment; group I comprised patients (n = 26) without antecedent antithrombin therapy; group II, pa tients (n = 30) with heparin infusion for ≥24 h, and group III patients (n = 23) with ongoing heparin infusion and given antithrombin III concentrate immediately before the procedure because of plasma antithrombin III <85%. Immediate results were 89% (70 of 79) angiographic suc cess, five (6%) subacute occlusions (two subsequent non-Q wave infarctions), no emergency coronary artery bypass grafting (CABG), and no immediate mortality. There were no differences between the groups. From dis charge to 4 months, one patient died, one had a nonfatal infarction, and 24 (30%) had repeated PTCA or CABG. The cumulative 4-month event rate was 11 of 26 (42%) in group I, 10 of 30 (33%) in group II, and 7 of 23 (30%) in group III (NS). During PTCA, heparin bolus administra tion was guided by activated clotting time (ACT), aiming at>300 s. Baseline ACT was significantly less in patients not treated with heparin (129 ± 34 s in group I vs. 179 ± 38 and 162 ± 29 s in groups II and III, respectively; p < 0.05), but during the procedure, patients from all groups required the same amount of heparin (13,900 ± 4,800, 13,000 ± 6,800, and 13,000 ± 5,700 IU, respectively; NS) to reach similar maximum ACT levels (334 ± 36, 312 ± 32, and 319 ± 44 s, respectively; NS). Patients receiving warfarin ( n = 8) responded with a higher ACT (456 ± 110 s; p < 0.05) on lower doses of heparin (10,000 ± 3,800 IU). In conclusion, patients with unstable angina receiv ing individualized antithrombotic therapy can be success fully treated with PTCA, with an acute complication rate and long-term results comparable with those expected in patients undergoing elective procedures. The value of an tithrombin III substitution must be evaluated in random ized trials. Preprocedural heparin infusion does not re duce the need of extra heparin during the procedure. Key Words: Antithrombin III—Heparin—PTCA (percutane ous transluminal coronary angioplasty)—Unstable angina pectoris.
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| 20. |
- Gupta, G., et al.
(författare)
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Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
- 2023
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Ingår i: Acs Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 17:17, s. 17451-17467
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.
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| 23. |
- Hage, C, et al.
(författare)
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Glycaemic control and restenosis after percutaneous coronary interventions in patients with diabetes mellitus: a report from the Insulin Diabetes Angioplasty study
- 2009
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Ingår i: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 6:2, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the impact of glucose control on target lesion restenosis after PCI in patients with type 2 diabetes. Methods: Ninety-three consecutive patients with type 2 diabetes accepted for PCI were randomised to intensified glucose control based on insulin (I-group; n=44) or to continue ongoing glucose-lowering treatment (C-group; n=49).The treatment target was a FBG of 5—7 mmol/L and HbA1c <6.5%. Information on target lesion restenosis after six months was available in 82 patients. Results: At baseline HbA1c and FBG did not differ between the I- and C-groups, respectively (HbA1c: 6.5 vs. 6.5%; p=1.0 and FBG: 7.0 vs. 7.3 mmol/L; p=0.3). After six months there was no significant change in HbA1c or FBG in either group (change in HbA1c: -0.2 vs.-0.1%; p=0.3 and in FBG: +0.2 vs. -0.3 mmol/L; p=0.3 in the I- and C-groups, respectively). Target lesion restenosis at six months did not differ, I vs. C = 41 and 44% (p=0.8). Independent predictors for restenosis were previous myocardial infarction (OR 8.0, 95% CI 2.5—25.7; p=<0.001) and FBG at baseline (OR for an increase by 1 mmol/L = 1.4, 95% CI 1.1—1.9; p=0.015). Conclusions: Restenosis was predicted by baseline FBG suggesting that it would be of interest to target glucose normalisation in future trials. Intensified insulin treatment did not influence the rate of restenosis indicating that the main focus should be on lowering glucose rather than the tool to normalise glucose.
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| 24. |
- Hagmar, L, et al.
(författare)
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Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose
- 2001
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 27:4, s. 219-226
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study assessed the health effects of occupational acrylamide exposure using hemoglobin (Hb) adducts as biomarkers of internal dose. METHODS: Two hundred and ten tunnel workers exposed for about 2 months to a chemical-grouting agent containing acrylamide and N-methylolacrylamide underwent a health examination. Blood samples were drawn for the analysis of Hb adducts of acrylamide. Fifty workers claiming recently developed or deteriorated symptoms of the peripheral nervous system (PNS) were referred to a neurophysiological examination. Workers with Hb-adduct levels exceeding 0.3 nmol/g globin attended follow-up examinations 6, 12, and 18 months after exposure cessation. RESULTS: Forty-seven workers had Hb-adduct levels within the normal background range (0.02-0.07 nmol/g globin), while the remaining 163 had increased levels up to a maximum of 17.7 nmol/g globin. Clear-cut dose-response associations were found between the Hb-adduct levels and PNS symptoms. Thirty-nine percent of those with Hb-adduct levels exceeding 1 nmol/g globin experienced tingling or numbness in their hands or feet. A no-observed adverse effect level of 0.51 nmol/g globin was estimated for numbness or tingling in the feet or legs. For 23 workers there was strong evidence of PNS impairment due to occupational exposure to acrylamide. All but two had recovered 18 months after the cessation of exposure. CONCLUSIONS: Occupational exposure to a grouting agent containing acrylamide resulted in PNS symptoms and signs. The use of Hb adducts of acrylamide as a biomarker of internal dose revealed strong dose-response associations. The PNS symptoms were, however, generally mild, and in almost all cases they were reversible.
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| 26. |
- Herlitz, Johan, et al.
(författare)
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Mortality and morbidity during a five-year follow-up of diabetics with myocardial infarction
- 1988
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 224:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- In 787 patients with acute myocardial infarction originally participating in the Göteborg Metoprolol Trial, mortality and morbidity during 5 years' follow-up were assessed and related to whether patients had diabetes mellitus. Diabetes occurred in 78 patients (10%). Patients with diabetes had a different risk factor pattern, including higher age, higher occurrence of angina pectoris and hypertension, whereas smoking habits did not differ. In the early phase (hospitalization), patients with diabetes had a higher mortality (12% versus 8%), required more treatment for heart failure and stayed longer in hospital. Other morbidity aspects, such as severity of pain, occurrence of severe supraventricular and ventricular arrhythmias, high-degree AV-block and infarct size did not differ. During 5 years' follow-up mortality rate in patients with diabetes mellitus was 55% as compared with 30% among patients with no diabetes (P<0.001). Reinfarction rate during 5 years was 42% in daibetics versus 25% in non-diabetics (P<0.001). In a multivariate analysis, taking into account the differences in risk factor pattern, diabetes turned out to be an independent determinant for long-term mortality and reinfarction (P<0.001). We conclude that patients with diabetes mellitus, developing acute myocardial infarction, is a group with particularly high risk of death and reinfarction. Interventions aiming at its reduction have priority.
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| 32. |
- Malmberg, K, et al.
(författare)
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Randomised trial of insuline-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI-Study) Effects on mortality at 1 year
- 1995
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Ingår i: Journal of the American College of Cardiology. - : Elsevier Inc.. - 0735-1097 .- 1558-3597. ; 26:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. Background. Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. Methods. A total of 620 patients were studied : 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for ≥3 months and 314 to conventional therapy. Results. The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 ± 4.1 to 9.6 ± 3.3 mmol/liter (mean ± SD) in the infusion group during the 1st 24 h, and from 15.7 ± 4.2 to 11.7 ± 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046] ; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). Conclusions. Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.
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| 36. |
- Mellbin, L. G., et al.
(författare)
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The relationship between glycaemic variability and cardiovascular complications in patients with acute myocardial infarction and type 2 diabetes: a report from the DIGAMI 2 trial
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:5, s. 374-379
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Tidskriftsartikel (refereegranskat)abstract
- AimsHyperglycaemia during hospitalization for acute myocardial infarction (AMI) is a risk predictor, but attempts to improve the prognosis by insulin-based glucose control have not been consistently successful. Increased glycaemic variability, a potential effect of insulin treatment, has been linked to a worse prognosis in critically ill patients. The present aim was to study the possibility of such a relation in patients with type 2 diabetes (T2DM) and AMI.Method and resultsWe studied 578 T2DM patients who had glucose levels measured hourly while receiving an insulin-glucose infusion during the first 48 h of hospitalization for AMI. Three measures of glycaemic variability: root mean square error (RMSE), range, and slope were studied in relation to a composite endpoint of mortality, stroke, and reinfarction and to mortality.In unadjusted analyses, the mean level of glycaemic variability did not differ between patients who died during 12 months of follow-up compared with those who survived. In a Cox regression model adjusting for age and previous congestive heart failure, there was no increased risk for the composite endpoint associated with increased glycaemic variability; RMSE: hazard ratio (HR) 1.09 [95% confidence interval (CI) 0.93-1.27; P = 0.28], range: HR 1.01 (95% CI: 0.98-1.05; P = 0.47), and slope: HR 1.01 (95% CI: 0.99-1.04; P = 0.40). There was furthermore no increased risk in mortality; RMSE HR 1.14 (95% CI: 0.93-1.38; P = 0.21), range HR 1.03 (95% CI: 0.98-1.08; P = 0.28), and slope HR 1.01 (95% CI: 0.98-1.04; P = 0.55).ConclusionThe 1-year risk for death, reinfarction, or stroke did not relate to glycaemic variability in T2DM patients with AMI treated with insulin infusion.
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| 42. |
- Reynolds, C. A., et al.
(författare)
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Sortilin receptor 1 predicts longitudinal cognitive change
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:6
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Tidskriftsartikel (refereegranskat)abstract
- The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.
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| 43. |
- Ritsinger, V., et al.
(författare)
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Elevated levels of adipokines predict outcome after acute myocardial infarction : A long-term follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort
- 2017
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Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 14:2, s. 77-87
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Adiponectin and leptin are associated with insulin resistance and cardiovascular disease. Information on the prognostic value after an acute myocardial infarction is still conflicting. Methods: Patients (n = 180) without known diabetes and with admission glucose of <11 mmol/L admitted for an acute myocardial infarction in 1998-2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/heart failure) until the end of 2011 (median: 11.6 years). Plasma adiponectin and leptin were related to outcome in Cox proportional-hazard regression analyses. Results: Median age was 64 years and 69% were male. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event. Adiponectin at discharge predicted cardiovascular events (hazard ratio; 95% confidence interval; 1.45; 1.02-2.07, p = 0.038), total mortality (2.53; 1.64-3.91, p < 0.001) and cancer mortality (3.64; 1.51-8.74, p = 0.004). After adjustment for age, sex, body mass index, previous myocardial infarction and heart failure, adiponectin predicted total mortality (1.79; 1.07-3.00, p = 0.027) but not cardiovascular events. High levels of leptin were associated with cardiovascular events during the first 7 years, after which the association was attenuated. Leptin did not predict total mortality. Conclusion: In patients with acute myocardial infarction but without previously known diabetes, high levels of adiponectin at discharge predicted total mortality. The present results support the hypothesis that high rather than low levels of adiponectin predict mortality after acute myocardial infarction.
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| 46. |
- Schrieks, I. C., et al.
(författare)
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Adiponectin, Free Fatty Acids, and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Acute Coronary Syndrome
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 41:8, s. 1792-1800
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio (Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus) trial, which compared the PPAR-alpha/gamma agonist aleglitazar with placebo. Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death. A twofold higher baseline adiponectin (n = 6,998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08-1.27]) and death (HR 1.53 [95% CI 1.35-1.73]). A doubling of adiponectin from baseline to month 3 (n = 6,325) was also associated with risk of death (HR 1.20 [95% CI 1.03-1.41]). Baseline FFAs (n = 7,038), but not change in FFAs from baseline (n = 6,365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment. In contrast to prior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes.
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| 47. |
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| 48. |
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| 49. |
- Stahli, B. E., et al.
(författare)
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Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With Diabetes and Acute Coronary Syndrome
- 2018
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:7, s. 2522-2533
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain. Design: The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-a/g agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results: In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events. Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.
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| 50. |
- Tobin, N. P., et al.
(författare)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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