FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Diabetes, prediabetes, and atrial fibrillation-A population-based cohort study based on national and regional registers.

BACKGROUND: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF. OBJECTIVE: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF. METHODS: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference. RESULTS: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF. CONCLUSIONS/INTERPRETATION: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

Rationale and design of switch Swedeheart: A registry-based, stepped-wedge, cluster-randomized, open-label multicenter trial to compare prasugrel and ticagrelor for treatment of patients with acute coronary syndrome.

BACKGROUND: European treatment guidelines recommend prasugrel over ticagrelor for treating patients with non-ST-elevation acute coronary syndrome (ACS), prompting several Swedish administrative regions to transition from ticagrelor to prasugrel as the preferred treatment for patients with ACS. We aim to systematically evaluate this transition to determine the relative efficacy of prasugrel versus ticagrelor in a real-world cohort of patients with ACS. STUDY DESIGN AND OBJECTIVES: The SWITCH SWEDEHEART trial is a prospective, multicenter, open-label, cross-sectional, stepped-wedge cluster-randomized clinical trial, in which administrative regions in Sweden will constitute the clusters. At the start of the study, all clusters will use ticagrelor as the P2Y12 inhibitor drug of choice for ACS. The order in which the clusters will implement the transition from ticagrelor to prasugrel will be randomly assigned. Every 9 months, 1 cluster will switch from ticagrelor to prasugrel as the P2Y12 inhibitor of choice for patients with ACS. The primary endpoint is the composite 1-year rate of the death, stroke, or myocardial infarction. CONCLUSIONS: The SWITCH SWEDEHEART study will provide an extensive randomized comparison between ticagrelor and prasugrel. Novel therapies are frequently costly and supported by evidence from few or small studies, and systematic evaluation after the introduction is rare. This study will establish an important standard for introducing and evaluating the effects of health care changes within our societies.

Notifications and alerts in patient dose values for computed tomography and fluoroscopy-guided interventional procedures.

The terms "notifications" and "alerts" for medical exposures are used by several national and international organisations. Recommendations for CT scanners have been published by the American Association of Physicists in Medicine. Some interventional radiology societies as well as national authorities have also published dose notifications for fluoroscopy-guided interventional procedures. Notifications and alerts may also be useful for optimisation and to avoid unintended and accidental exposures. The main interest in using these values for high-dose procedures (CT and interventional) is to optimise imaging procedures, reducing the probability of stochastic effects and avoiding tissue reactions. Alerts in X-ray systems may be considered before procedures (as in CT), during procedures (in some interventional radiology systems), and after procedures, when the patient radiation dose results are known and processed. This review summarises the different uses of notifications and alerts to help in optimisation for CT and for fluoroscopy-guided interventional procedures as well as in the analysis of unintended and accidental medical exposures. The paper also includes cautions in setting the alert values and discusses the benefits of using patient dose management systems for the alerts, their registry and follow-up, and the differences between notifications, alerts, and trigger levels for individual procedures and the terms used for the collective approach, such as diagnostic reference levels. KEY POINTS: • Notifications and alerts on patient dose values for computed tomography (CT) and fluoroscopy-guided interventional procedures (FGIP) allow to improve radiation safety and contribute to the avoidance of radiation injuries and unintended and accidental exposures. • Alerts may be established before the imaging procedures (as in CT) or during and after the procedures as for FGIP. • Dose management systems should include notifications and alerts and their registry for the hospital quality programmes.

IL-6 as a Mediator of the Association Between Traditional Risk Factors and Future Myocardial Infarction: A Nested Case-Control Study.

[Figure: see text].

Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction.

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case-control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02-3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06-3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.

G Protein-Coupled Receptor 15 Expression Is Associated with Myocardial Infarction.

Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case−control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (ß = 0.8498, p = 0.111), C-reactive protein (ß = 0.2238, p = 0.0052), ejection fraction (ß = −0.9991, p = 0.0281) and smoking (ß = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

Smoking tobacco is associated with renal hyperfiltration.

Tobacco consumption is a renal risk factor, but the effects on the estimated glomerular filtration rate (eGFR) remain unclear. We aimed to evaluate the possible impact of using tobacco products (smoking and snus) on eGFR based on creatinine or cystatin C. We used a first cohort with 949 participants and a second cohort with 995 participants; none had pre-existing renal disease. All subjects donated a blood sample and completed a questionnaire, including questions about tobacco use. To assess the effect on eGFR, hierarchical multiple linear regression models were used. Active smoking associated independently with a higher eGFRcreatinine in all subjects (p < 0.001; ß = 0.11). Further analyses stratified for sex, showed similar findings for men (p < 0.001; ß = 0.14) and for women (p = 0.026; ß = 0.10). eGFRcystatin C was significantly associated with active smoking in all subjects (p = 0.040; ß = -0.05), but no association was seen after stratification for sex. Snus did not associate with eGFR. In conclusion, smoking associated significantly with a higher eGFRcreatinine. The mechanism may be renal hyperfiltration of smaller molecules such as creatinine. This is probably caused by substances from smoked tobacco other than nicotine, as no effect was seen for snus.

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk of a future first-ever myocardial infarction in women.

Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called 'Shrunken Pore Syndrome' has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFRcystatin C) is affected earlier due to differences in molecular size compared to eGFRcreatinine. The aim was to investigate if a lower eGFRcystatin C/eGFRcreatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFRcystatin C/eGFRcreatinine ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34-0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFRcreatinine associated independently with an increased risk of future MI in men only: OR 1.25 [1.05-1.48]. Thus, for women, a lower eGFRcystatin C/eGFRcreatinine ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease.

Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease.

BACKGROUND: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). METHODS: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Applying three different methods of measuring CTDIfree air to the extended CTDI formalism for wide-beam scanners (IEC 60601-2-44): A comparative study.

PURPOSE: The weighted CT dose index (CTDIw ) has been extended for a nominal total collimation width (nT) greater than 40 mm and relies on measurements of CTDIfreeair. The purpose of this work was to compare three methods of measuring CTDIfreeair and subsequent calculations of CTDIw to investigate their clinical appropriateness. METHODS: The CTDIfreeair, for multiple nTs up to 160 mm, was calculated from (1) high-resolution air kerma profiles from a step-and-shoot translation of a liquid ionization chamber (LIC) (considered to be a dosimetric reference), (2) pencil ionization chamber (PIC) measurements at multiple contiguous positions, and (3) air kerma profiles obtained through the continuous translation of a solid-state detector. The resulting CTDIfreeair was used to calculate the CTDIw , per the extended formalism, and compared. RESULTS: The LIC indicated that a 40 mm nT should not be excluded from the extension of the CTDIw formalism. The solid-state detector differed by as much as 8% compared to the LIC. The PIC was the most straightforward method and gave equivalent results to the LIC. CONCLUSIONS: The CTDIw calculated with the latest CTDI formalism will differ most for 160 mm nTs (e.g., whole-organ perfusion or coronary CT angiography) compared to the previous CTDI formalism. Inaccuracies in the measurement of CTDIfreeair will subsequently manifest themselves as erroneous calculations of the CTDIw , for nTs greater than 40 mm, with the latest CTDI formalism. The PIC was found to be the most clinically feasible method and was validated against the LIC.

Outcomes 1 year after thrombus aspiration for myocardial infarction.

BACKGROUND: Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration. METHODS: We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial. RESULTS: No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients (191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6% (202 of 3623) in the PCI-only group (hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P=0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively (hazard ratio, 0.97; 95% CI, 0.73 to 1.28; P=0.81), and stent thrombosis in 0.7% and 0.9%, respectively (hazard ratio, 0.84; 95% CI, 0.50 to 1.40; P=0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively (hazard ratio, 0.94; 95% CI, 0.80 to 1.11; P=0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI. CONCLUSIONS: Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year. (Funded by the Swedish Research Council and others; TASTE ClinicalTrials.gov number, NCT01093404.).

Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1.

Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.

Dietary inflammatory index and risk of first myocardial infarction; a prospective population-based study.

BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DIITM), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up. METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population. RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available. CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

If you can make it, you can share it - Perspectives on the first DIY-fair at the European congress of medical physics (ECMP, DUBLIN 2022).

The medical physics and engineering community is known for being active in conjuring do-it-yourself (DIY) -solutions to support their clinical and research work. To facilitate the exchange of solutions and ideas, a DIY-fair was held for the first time at the European Congress of Medical Physics (ECMP) in August 2022 in Dublin, Ireland. Altogether 32 contributions were presented, consisting of software, scripts, 3D-printed customized solutions, devices, gadgets and phantoms. All contributions were published in video format on a dedicated YouTube channel, and most were also presented in person at the conference. The fair demonstrated that there is an unmet need for sharing and distributing information on self-created solutions in the medical physics community. The authors propose the creation of a dedicated platform for sharing such content within our community, as well as a continuity of DIY-fairs at future ECMP meetings.

E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs. OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion. METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells. CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.

Abbreviated Versus Standard Dual Antiplatelet Therapy Times After Percutaneous Coronary Intervention in Patients With High Bleeding Risk With Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS AND RESULTS: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P=0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. CONCLUSIONS: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.