| 1. |
- Bech-Hanssen, Odd, 1956, et al.
(författare)
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Pressure reflection in the pulmonary circulation in patients with severe mitral regurgitation indicates adverse postoperative outcome.
- 2013
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Ingår i: European Journal Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 44:6, s. 1037-1044
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Severe pulmonary hypertension (PH) is a known risk factor in valvular surgery. In the present study, we hypothesized that the assessment of pressure reflection (PR) in the pulmonary circulation, indicating increased pulmonary vascular resistance, might improve the identification of patients with increased morbidity and mortality following surgery for severe mitral regurgitation. METHODS: A total of 103 patients without atrial fibrillation were divided into three groups: Group 1 (n = 48), patients without PR; Group 2 (n = 36), patients with PR and pulmonary artery systolic pressure (PASP) ≤60 mmHg and Group 3 (n = 19), patients with PR and PASP >60 mmHg. Three variables related to PR were selected: the acceleration time in the right ventricular outflow tract (RVOT), the interval between peak velocity in the RVOT and peak tricuspid regurgitant jet velocity and the right ventricular pressure increase after peak RVOT velocity. RESULTS: There were no differences between groups in age, ejection fraction, need for coronary bypass grafting or creatinine. Patients with PR (Groups 2 and 3) had more use of vasoactive drugs (overall P < 0.0001, Group 1 vs Group 2 P = 0.018). The proportion of patients with >24 h in the intensive care unit was 27% in Group 1, 54% in Group 2 and 84% in Group 3 (overall P < 0.0001, Group 1 vs Group 2 P = 0.006). The in-hospital mortality in patients without PR (n = 49) was 0% compared with 10.9% in patients with PR (P = 0.029). CONCLUSIONS: Echocardiography assessment of PR in the pulmonary circulation and severe PH may identify patients with adverse outcome following mitral surgery.
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| 2. |
- Berkenstam, Anders, et al.
(författare)
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The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:2, s. 663-667
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115, (3-[[3,5-dibromo-4- [4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis. © 2007 by The National Academy of Sciences of the USA.
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| 3. |
- Bhat, Misha, et al.
(författare)
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Longitudinal ECG changes in tetralogy of Fallot and association with surgical repair
- 2024
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Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: ECG abnormalities have been linked to adverse changes in right ventricular (RV) morphology and poor clinical outcomes in repaired Tetralogy of Fallot (rTOF). Our aim was to describe how ECG changes progress in early and intermediate follow-up and whether types of surgical strategy at the time of primary repair affected these changes. Methods: We studied patients with rTOF born 2000–2018 operated at our institution. Seven time points in relation to primary repair, follow-up, and pulmonary valve replacement (PVR) were identified. Patients correct with valve sparing repair (VSR), trans-annular patch (TAP) including with a monocusp valve (TAP + M) and with at least 3 ECGs were included. PQ interval, QRS duration, dispersion, and fragmentation, QTc duration and dispersion, JTc as well as presence of a right bundle branch block (RBBB) were analyzed. Medical records were reviewed for demographic and surgical data. Results: Two hundred nineteen patients with 882 ECGs were analyzed with a median follow-up time of 12.3 years (8.4, 17) with 41 (19%) needing PVR during the study period. QRS duration increased at time of primary repair to discharge from 66 msec (IQR 12) to 129 msec (IQR 27) (p < 0.0001) and at 1- and 6- year follow-up but showed only a modest and temporary decrease after PVR. QTc increased at the time of primary repair as well as prior to PVR. PQ interval showed a small increase at the time of primary repair, was at its highest prior to PVR and decreased with PVR. Type of surgical repair affected mainly QTc and JTc and was consistently longer in the TAP + M group until PVR. In VSR, QTc and JTc were prolonged initially compared to TAP but were similar after 1 year. After PVR, there were no differences in adverse ECG changes between surgical groups. Conclusions: PQ interval and QRS duration best correspond to the assumed volume load whereas the relationship with QTc and JTc is more complex, suggesting that these represent more complex remodeling of the myocardium. Before PVR, QTc and JTc are longer in the TAP + M group which may be due to a longer surgical incision.
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| 4. |
- Björklund, Erik, et al.
(författare)
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Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome.
- 2021
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak.To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy.This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020.Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only.Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up.A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P=.34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P=.29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P=.011). Sensitivity analyses confirmed the results.In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.
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| 5. |
- Björklund, Erik, et al.
(författare)
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Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting
- 2023
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Ingår i: HEART. - 1355-6037 .- 1468-201X.
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction.Methods All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk.Results Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event.Conclusions The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.
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| 6. |
- Björklund, Erik, et al.
(författare)
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Postoperative platelet function is associated with severe bleeding in ticagrelor-treated patients
- 2019
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 28:5, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Preoperative testing of platelet function predicts bleeding risk in cardiac surgery patients treated with dual antiplatelet therapy, but the value of postoperative platelet function testing, reflecting both preoperative antiplatelet therapy and perioperative changes in platelet function, has not been evaluated. Methods: Seventy-four patients with acute coronary syndrome treated with acetylsalicylic acid and ticagrelor within 5 days before cardiac surgery were included in a prospective observational study. Platelet aggregation induced by adenosine diphosphate, arachidonic acid and thrombin receptor-activating peptide was assessed with multiple electrode impedance aggregometry immediately before surgery and 2 h after weaning off cardiopulmonary bypass. Receiver operating characteristic curves were used to determine any association between platelet aggregation and severe bleeding according to the universal definition of perioperative bleeding in adult cardiac surgery. Results: Severe bleeding occurred in 25 of 74 patients (34%). Preoperative and postoperative adenosine diphosphate-induced platelet aggregations were associated with bleeding, with comparable areas under the receiver operating characteristic curve [0.77 (95% confidence interval 0.65-0.89) vs 0.75 (0.62-0.87)]. Postoperative arachidonic acid-and thrombin receptor-activating peptide-induced aggregation had markedly smaller areas under the curve. There were significant correlations between preoperative and postoperative platelet aggregation induced by adenosine diphosphate (r2 = 0.77, P < 0.001), arachidonic acid (r2 = 0.24, P < 0.001) and thrombin receptoractivating peptide (r2 = 0.21, P < 0.001) but with large interindividual variations. Conclusions: Poor postoperative platelet function was associated with severe bleeding, with accuracy comparable to that of preoperative platelet function. There was a correlation between preoperative and postoperative platelet function, but the predictability in an individual patient was limited. © 2018 The Author(s). Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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| 7. |
- Björklund, Erik, et al.
(författare)
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Secondary prevention medications after coronary artery bypass grafting and long-term survival : a population-based longitudinal study from the SWEDEHEART registry.
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:17, s. 1653-1661
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the long-term use of secondary prevention medications [statins, β-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality.METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for β-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between β-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54).CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of β-blockers may be questioned.
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| 8. |
- Giwercman, Aleksander, et al.
(författare)
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Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.
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| 9. |
- Gäbel, Jakob, 1971, et al.
(författare)
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Cell saver processing mitigates the negative effects of wound blood on platelet function
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 60:7, s. 901-909
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWound blood is highly activated and has poor haemostatic properties. Recent data suggest that retransfusion of unwashed wound blood may impair haemostasis. We hypothesized that cell saver processing of wound blood before retransfusion reduces the negative effects. MethodsWound blood was collected from 16 cardiac surgery patients during cardiopulmonary bypass. One portion of the wound blood was processed in a cell saver and one portion left unprocessed. Increasing amounts of unprocessed blood (10% and 20% of the systemic blood volume) or corresponding volumes of processed blood were added ex vivo to whole blood samples from the same patient. Clot formation was assessed by modified thromboelastometry (ROTEM (R)) and platelet function with impedance aggregometry (Multiplate((R))). ResultsAddition of unprocessed wound blood significantly impaired clot formation and platelet aggregability. Cell saver processing before addition did not influence clot formation but abolished completely the negative effects of wound blood on platelet aggregability tested with all agonists. Median adenosine diphosphate-induced platelet aggregation was 51 (25th and 75th percentiles 42-69) when 20% processed cardiotomy suction blood was added vs. 34 (24-52) U when 20% unprocessed blood was added, P < 0.001. The corresponding figures for arachidonic acid-, thrombin receptor activating peptide- and collagen-induced aggregation was 21 (17-51) vs. 13 (10-25) U, 112 (87-128) vs. 78 (65-103) U and 58 (50-73) vs. 33 (28-44) U, respectively, all P < 0.001). ConclusionThe results suggest that cell saver processing before retransfusion mitigates the negative effects of wound blood on platelet function despite that cell saver processing reduces platelet count.
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| 10. |
- Hansson, Emma C., 1985, et al.
(författare)
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Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery
- 2017
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 51:4, s. 633-637
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dual antiplatelet therapy with ticagrelor and aspirin is associated with an increased risk of perioperative bleeding complications. Current guidelines recommend therefore discontinuation of ticagrelor 5 days before surgery to allow sufficient recovery of platelet function. It is not known how the time to recovery varies between individual patients after discontinuation of ticagrelor. METHODS: Twenty-five patients accepted for urgent coronary artery bypass surgery and treated with ticagrelor and aspirin were included in a prospective observational study. Platelet aggregation was evaluated with impedance aggregometry at five timepoints 12-96 h after discontinuation of ticagrelor. In a subset of patients (n = 15), we also tested the ex vivo efficacy of platelet concentrate supplementation on platelet aggregation. RESULTS: There was a gradual increase in mean adenosine diphosphate-induced platelet aggregation after discontinuation of ticagrelor. After 72 h, mean aggregation was 38 +/-23 aggregation units (U), which is above a previously suggested cut-off of 22 U, when patients can be operated without increased bleeding risk. However, there was a large interindividual variability (range 488 U at 72 h) and 6/24 patients (25%) had <22 U after 72 h. Ex vivo administration of platelet concentrate did not improve adenosine diphosphate-induced aggregation at any timepoint after ticagrelor discontinuation. CONCLUSIONS: Adenosine diphosphate-induced aggregation was acceptable after 72 h in the majority of patients but with a large interindividual variability. Due to the large variability, platelet function testing may prove to be a valuable tool in timing of surgery in patients with ongoing or recently stopped ticagrelor treatment. Adenosine diphosphate-induced aggregation was not improved by addition of platelet concentrate.
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| 11. |
- Kihlstedt, Carl-Johan, et al.
(författare)
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Freezing of gait in idiopathic normal pressure hydrocephalus
- 2024
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG’s responsiveness to shunt surgery.Methods: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71–79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared.Results: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups.Conclusions: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.
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| 12. |
- Malm, Carl Johan
(författare)
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Cardiac surgery and antiplatelet therapy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and a P2Y12 inhibitor improves outcome in acute coronary syndrome (ACS). In the subset of ACS patients undergoing urgent cardiac surgery, ongoing or recently discontinued DAPT is associated with increased risk of bleeding. Postoperative DAPT in ACS patients after coronary artery bypass grafting (CABG) may improve graft patency and short-term survival. The aim of this project was to study ACS patients undergoing cardiac surgery and how DAPT with ASA and ticagrelor influences perioperative bleeding risks, how bleeding can be treated, and to investigate if survival after CABG is influenced by antiplatelet therapy. Methods In paper I, recovery of platelet function after discontinuation of ticagrelor was investigated using multiple-electrode aggregometry (MEA) in ACS patients awaiting CABG. The effect of platelet concentrate at different discontinuation times was also studied. Paper II was a prospective observational study of patients undergoing cardiac surgery with ongoing or recently discontinued ticagrelor treatment. The relationship between preoperative MEA and postoperative bleeding was investigated. In paper III, MEA was used to investigate the effect of aprotinin and tranexamic acid on platelet function in ACS patients with ongoing DAPT using ASA and ticagrelor. Paper IV was a nationwide study of all ACS patients undergoing isolated CABG surgery during a four-year period. The influence of postoperative antiplatelet therapy on one- year mortality was investigated using propensity score matching. Results Mean platelet ADP-induced aggregation increased gradually after ticagrelor discontinuation and reached normal values after 72–96 hours. There was a large inter-individual variability. Platelet concentrate did not improve ADP- induced aggregation at any time, but markedly increased arachidonic acid- induced aggregation at all time points. Preoperative ADP-induced aggregation predicted severe bleeding complications, with an optimal cut-off of 22 aggregation units. Aprotinin, but not tranexamic acid increased ADP-induced aggregation in patients with ongoing DAPT using ASA and ticagrelor. Postoperative treatment with ASA + ticagrelor was associated with a reduced one-year mortality compared to ASA only (hazard ratio 0.42, p=0.020). Conclusions Platelet function testing improved the assessment of the operative risk in ticagrelor treated patients. Platelet transfusion have no or limited effect in treating bleeding in patients with recent ticagrelor therapy. From a platelet function perspective, aprotinin may be preferred over TA in ticagrelor treated patients. Survival after CABG in ACS patients is likely influenced by postoperative antiplatelet therapy, with improved outcome associated with ticagrelor treatment.
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| 13. |
- Malm, Carl Johan, et al.
(författare)
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Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 259, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investor-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.
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| 14. |
- Malm, Carl Johan, et al.
(författare)
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Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study
- 2016
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 117:3, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment with P2Y(12) receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients. Methods: Ninety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index. Results: The median time from the last ticagrelor dose to surgery was 35 (range 4-108)h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63-0.84, P<0.001); TRAP 0.61 (0.49-0.74); AA 0.53 (0.40-0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively. Conclusions: Preoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.
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| 15. |
- Malm, Carl Johan, et al.
(författare)
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Small calibre biosynthetic bacterial cellulose blood vessels: 13-months patency in a sheep model.
- 2012
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 46:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives. Many patients in need of bypass surgery lack graft material and current synthetic alternatives have poor performance. A 4 mm vascular graft composed of bacterial cellulose (BC) was developed and tested in pilot study in a large animal model. Design. BC is a biopolymer made by the bacteria acetobacter xylinum. BC grafts (n = 16) with 4 cm length and 4 mm internal diameter were implanted bilaterally in the carotid arteries of eight sheep. No long-term antithrombotic therapy was administered. Patency was assessed with ultrasound. Histology, immunohistochemistry, and electron microscopy were performed after explantation. Results. Fifty percent of the grafts occluded within two weeks. One animal died with patent grafts after 14 days. In the three remaining animals 5/6 grafts were patent after nine months. Two animals were followed 13 months after implantation with 3/4 grafts patent at explantation. All patent grafts had confluent endothelial-like cells. Conclusions. Biosynthetic small calibre vascular grafts made from BC can be patent for up to 13 months in sheep carotid arteries. BC is a potential material for small calibre grafts but patency in animal models needs to be improved before clinical studies can be planned.
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| 16. |
- Malm, Johan, et al.
(författare)
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Isolation and characterization of the major gel proteins in human semen, semenogelin I and semenogelin II
- 1996
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 238:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- Semenogelin I and semenogelin II constitute the major gel-forming proteins in human semen. The gel proteins were rapidly solubilized and separated from spermatozoa in ejaculates collected at pH 9.7 in buffer containing 4 mol/l urea and dithiothreitol. This protected the semenogelins from proteolytic degradation by prostate-specific antigen, and allowed their isolation by affinity chromatograph:g on heparin-sepharose. Semenogelins I and II were almost selectively retained and eluted partially separated in 0.25 mol/l NaCl. Further purification was achieved by chromatography on Superose. Approximately 10-20 mg semenogelin I and 2-5 mg semenogelin II were recovered from each sample with a purity exceeding 95% as judged by SDS/PAGE. The molecular mass of semenogelin I (49,958 Da) and the major form of semenogelin II (63,539 Da) measured by mass spectrometry was consistent with the reported cDNA data. The occurrence of a second, larger form of semenogelin II was due to asparagine-linked glycosylation. The amino-termini of the purified proteins were blocked, but digestion with pyroglutamate aminopeptidase enabled the identification of amino-terminal sequences consistent with the reported cDNA data. The amino acid compositions of the purified proteins were also consistent with those derived from cDNA data. The absorption coefficients (280 nm, 1%, 1 cm) for semenoaelins I and II. were 5.5 and 5.4, respectively, and the isoelectric point was above pH 9.5 for both proteins.
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| 17. |
- Martinsson, Andreas, et al.
(författare)
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Renin-angiotensin system inhibition and outcome after coronary artery bypass grafting: A population-based study from the SWEDEHEART registry
- 2021
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 331, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renin-angiotensin system (RAS) inhibitors are recommended postoperatively to coronary artery bypass grafting (CABG) patients with reduced left ventricular function, diabetes, hypertension or previous myocardial infarction, but not to remaining patients. The aim of the study was to assess the long-term utilization of RAS inhibitors after CABG in patients with and without indication for treatment, and its association with outcome. Methods: All patients (n = 28,782) not meeting exclusion criterion in Sweden who underwent isolated first time CABG from 2006 to 2015 were included using nationwide registries. The association between treatment and outcome was assessed using adjusted Cox regression models with time-updated data on medications. The primary outcome was major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke and/or myocardial infarction. Results: At baseline 26,284 (91.3%) of the patients had at least one indication for RAS inhibition while 2498 (8.7%) had not. RAS inhibitors were dispensed to 77.0% and 29.7% of patients with and without indication respectively. Dispense declined over time. RAS inhibition was associated with a reduction in MACE in the whole study population (adjusted hazard ratio (aHR) 0.88, 95% confidence interval (95% CI) 0.83–0.93, p < 0.0001), and in patients with (aHR 0.87 95% CI: 0.82–0.93, p < 0.0001) and without indication (aHR 0.75, 95% CI: 0.58–0.98, p = 0.034). Conclusions: RAS inhibition is underutilized after CABG. The use of RAS inhibitors was associated with a reduction in MACE, both in patients with and without indication for treatment. The results suggest that RAS inhibition is beneficial for all CABG patients. Randomized controlled trials are necessary to confirm this hypothesis. © 2021 The Authors
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| 18. |
- Nielsen, Susanne, 1969, et al.
(författare)
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Socioeconomic Factors, Secondary Prevention Medication, and Long-Term Survival After Coronary Artery Bypass Grafting: A Population-Based Cohort Study From the SWEDEHEART Registry.
- 2020
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Low income and short education have been found to be independently associated with inferior survival after coronary artery bypass grafting (CABG), whereas the use of secondary prevention medications is associated with improved survival. We investigated whether underusage of secondary prevention medications contributes to the inferior long-term survival in CABG patients with a low income and short education. Methods and Results Patients who underwent CABG in Sweden between 2006 to 2015 and survived at least 6months after discharge (n=28448) were included in a population-based cohort study. Individual patient data from 5 national registries, including the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry, covering dispensing of secondary prevention medications (statins, platelet inhibitors, β-blockers, and RAAS inhibitors), socioeconomic factors, patient characteristics, comorbidity, and long-term mortaity were merged. All-cause mortality risk was estimated using multivariable Cox regression models adjusted for patient characteristics, baseline comorbidities, time-updated secondary prevention medications, and socioeconomic status. Long-term mortality was higher in patients with a low income and short education. Statins and platelet inhibitors were dispensed less often to patients with a low income, both at baseline and after 8years. The decline in dispensing over time was steeper for low-income patients. Short education was not associated with reduced dispensing of any secondary prevention medication. Use of statins (adjusted hazard ratio=0.57 [95% CI, 0.53-0.61]), RAAS inhibitors (adjusted hazard ratio=0.78 [0.73-0.84]), and platelet inhibitors (adjusted hazard ratio=0.74 [0.68-0.80]) were associated with reduced long-term mortality irrespective of socioeconomic status. Conclusions Secondary prevention medications are dispensed less often after CABG to patients with low income. Underusage of secondary prevention medications after CABG is associated with increased mortality risk independently of income and extent of education.
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| 19. |
- Nilsson, Tobias S, et al.
(författare)
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Hemofiltration in exvivo lung perfusion-a study in experimentally induced pulmonary edema.
- 2016
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Ingår i: The Journal of thoracic and cardiovascular surgery. - : Elsevier BV. - 1097-685X .- 0022-5223. ; 151:2, s. 570-75
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Tidskriftsartikel (refereegranskat)abstract
- Exvivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight.
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| 20. |
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| 21. |
- Singh, Sukhi, 1990, et al.
(författare)
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Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor-treated patients
- 2018
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Ingår i: Research and Practice in Thrombosis and Haemostasis. - : John Wiley & Sons. - 2475-0379. ; 2:4, s. 718-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Temporarily improved platelet reactivity may reduce the bleeding in patients on antiplatelet therapy who have ongoing bleeding or who are in need of acute surgery. Adrenaline can bind to adrenergic alpha(2A)-receptors on platelets and potentially enhance platelet reactivity.Objective: To assess if adrenaline can improve adenosine diphosphate (ADP)-induced platelet aggregation and activation in blood samples from patients on dual antiplatelet therapy with acetylsalicylic acid (ASA) and the ADP-receptor antagonist ticagrelor.Methods: Blood samples were collected from a total of forty acute coronary syndrome patients on dual antiplatelet therapy with ASA and ticagrelor. ADP-induced platelet aggregation (by impedance aggregometry) and activation (by flow cytometry) were assessed before and after supplementation with adrenaline and/or platelet concentrate.Results: Adrenaline supplementation (770 nmol L-1) increased median ADP-induced aggregation from 15 (25-75th percentiles: 10-20) to 26 (18-38) aggregation units. The effect was independent of concomitant platelet supplementation. Adrenaline also increased ADP-induced platelet activation: from 40% (36-54%) to 83% (74-88%) platelets with active fibrinogen receptor (binding PAC-1) and from 13% (7-21%) to 35% (18-50%) P-selectin-expressing platelets.Conclusions: Adrenaline potentiated ADP-induced platelet aggregation and activation in blood samples from ticagrelor-treated patients. Adrenaline infusion may be a new method to enhance platelet function in ticagrelor-treated patients who are in need of acute surgery or have ongoing bleeding. In vivo studies are needed to confirm the present results.
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| 22. |
- Smirnova, Joulia, et al.
(författare)
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An organoiron approach to thyroid hormone analogues
- 2005
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Ingår i: Journal of Organo metallic Chemistry. - : Elsevier BV. - 0022-328X. ; 690, s. 1784-1792
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Tidskriftsartikel (refereegranskat)abstract
- An approach to thyroid hormone analogues was proposed involving sequential substitution of cationic cyclopentadienyl(1.4-dichlorobenzene)iron(II) complexes with phenoxide/thiophenoxide and hydroxide/amine, followed by decomplexation. Although the selectivity for monosubstitution with phenolates and thiophenolates was poorer than previously observed, it was often possible to control the reaction with sterically less demanding phenolates of intermediate nucleophilicity. The subsequent introduction of a polar substituent into the monosubstituted product was successful with amine nucleophiles. A modified approach, based on the reverse order of substitution was also attempted. Whereas clean monosubstitution with hydroxide/hydroxide equivalents was unsuccessful, cyclopentadienyl(N-alkyl-1-chloro-4-aminobenzene)iron(II) complexes could be prepared in fair yields and further substituted with nucleophiles such as thiophenolates.
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| 23. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 24. |
- Wallgren, Sara, et al.
(författare)
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A single sequential snake saphenous vein graft versus separate left and right vein grafts in coronary artery bypass surgery: a population-based cohort study from the SWEDEHEART registry
- 2019
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 56:3, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Our goal was to compare short- and midterm outcomes after coronary artery bypass grafting (CABG) using 2 different revascularization strategies.A total of 6895 patients were included who had CABG in Sweden from 2009 to 2015 using the left internal mammary artery to the left anterior descending artery and either a single sequential saphenous vein graft connecting the left and right coronary territories to the aorta (snake graft, n=2122) or separate vein grafts to both territories (n=4773). Data were obtained from the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and the Swedish Patient Registry. The groups were compared using adjusted logistic regression for short-term (30-day) and Cox regression and flexible parametric survival models for midterm outcomes. Primary outcome was a composite of all-cause mortality, myocardial infarction (MI), reangiography and new revascularization. The median follow-up time was 35months.At 30days, the incidences of the composite end point [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.03-1.68; P=0.03] and reangiography (OR 1.51, 95% CI 1.07-2.14; P=0.02) were higher in the snake group. There was also a trend towards higher mortality (OR 1.47, 95% CI 0.97-2.22; P=0.07). The event rates during the complete follow-up period were 6.5 (5.9-7.2) and 5.7 (5.3-6.1) per 100 person-years for the snake group and the separate vein group, respectively. At the midterm follow-up, no significant difference between the groups could be shown for the composite end point [hazard ratio (HR) 1.08, 95% CI 0.95-1.22; P=0.24], mortality (HR 0.95, 95% CI 0.79-1.14; P=0.56), MI (HR 1.11, 95% CI 0.88-1.41; P=0.39) or new revascularization (HR 1.19, 95% CI 0.94-1.50; P=0.15), whereas reangiography remained more common in the snake group (HR 1.25, 95% CI 1.05-1.48; P=0.01).Snake grafts were associated with a higher rate of early postoperative complications, possibly reflecting a more demanding surgical technique, whereas midterm outcomes were comparable. Based on these data, one strategy cannot be recommended over the other.
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