bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incident cardiovascular events and risk of subsequent cancer diagnosis
Authors: Fardman A , Oppenheim A , Banschick G.D , Rabia R , Segev S , Klempfner R , Fourey D , Percik R , Grossman E , Maor E 
Published: November 2020

Abstract

Background
Cardiovascular disease (CVD) and cancer share common risk factors. This study investigated the association of CVD diagnosis and the risk of future cancer.

Methods
We evaluated asymptomatic self-referred adults aged 40–79 years who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention or stroke. Cancer and mortality data were available for all subjects from national registries. Primary end-point was development of cancer during follow up. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event.

Results
Final study population included 15,486 subjects. Median age was 50 years (Interquartile range [IQR] 44–55) and 72% were men. During median follow up time of 11 years (IQR 6–15) 1,028 (7%) subjects developed CVD, 1,281 (8%) developed cancer and 499 (3%) died. Most common cancer types were prostate among men (N=277, 1.8%) and breast among women (N=187, 1.2%). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop cancer (95% Confidence Interval [CI] 1.3–1.95, p&lt;0.001). However, after adjustment for known predictors of cancer, the association of incident CVD with cancer diagnosis was no longer significant (p=0.21). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (&lt;50 years; N=7,649) incident CVD was associated with a significant 2 fold increased risk of subsequent cancer diagnosis (95% CI 1.2–3.6, p=0.014) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =0.035; Figure 1).

Conclusions
Incident CVD is independently associated with 2-fold increased risk of subsequent cancer diagnosis among young adults. Our analysis underscores the importance of cancer surveillance among young patients following a CVD event.
Figure 1

Funding Acknowledgement
Type of funding source: None
Amygdalar activity among patients with head and neck cancer predicts cerebrovascular events: a retrospective FDG PET/CT Cohort Study
Authors: Hassan M , Abohashem S , Wang Y , Jones O'connor M , Alvi R.M , Zlotoff D.A , Bakar R.B , Osborne M.T , Chan A.W , Wirth L.J , Awadalla M.A , Addison D , Tawakol A , Neilan T 
Published: November 2020

Abstract

Background
Radiation therapy for head and neck cancer (HNC) associates with an increase in cerebrovascular events. Amygdalar metabolic activity (AmygA), a measure of stress-associated neurobiological activity, associates with cardiovascular events in patients without cancer. In this study, we tested whether AmygA was associated with cerebrovascular events among patients treated with radiation therapy.

Methods
The associations between AmygA (at cancer staging) and subsequent cerebrovascular events as well as inflammatory biomarkers and arterial inflammation, were tested among consecutive patients with HNC treated with radiation therapy who underwent 18F-FDG-PET/CT.

Results
Among 240 patients (59±13 years; 30% female, 48% had stage 4 disease), there were 26 events over a median follow-up period of 3 years (IQR: 1.7–5.1). AmygA at cancer staging was associated with subsequent cerebrovascular events, an effect that remained significant after adjustment for age, sex, and cerebrovascular risk factors (adjusted hazard ratio 1.47, 95% CI 1.04–2.09, P=0.031). The association persisted when the analysis was restricted to patients with no prior history of CV disease and even among those with lower predicted CV risk (P&lt;0.001). Higher AmygA at cancer staging also associated with serum inflammatory markers and arterial inflammation (P&lt;0.05 each).

Conclusions
Amygdalar activity, a quantifiable biomarker of stress-associated brain activity, associated with subsequent cerebrovascular events among patients with cancer treated with radiation therapy.

Funding Acknowledgement
Type of funding source: None
Mitochondrial dysfunction associated with AC mode of chemotherapy intake
Authors: Avagimyan A.A , Mrochek A.G , Sarrafzadegan N , Konradi A.O , Aznauryan A.V , Chernova A.A , Oganov R.G , Mkrtchyan L.H , Ionov A.Y.U , Chelidze K.H , Petrosyan R.R , Petrosyan A.R , Aznauryan A.Z , Navasardyan G.A , Ostoumova O.D 
Published: November 2020

Abstract

Since the establishment of the anthracycline drugs cardiotoxigenic effect, the most widely accepted mechanistic base for their iatrogenic cardiotoxicity was connected with excessive and inadequate intensification of LPO. However, ineffectiveness of the antioxidant and multivitamin regimens of cardio-protection caused the necessity of finding new pathogenic targets, exposure to which will prevent the development of cardiovascular symptoms. Such a target became the nuclear topoisomerases, the study results of which served as the foundation for the creation of dexrazoxan, the only drug with this regard approved by the FDA. However, our interest was attracted towards the mitochondrial topoisomerases, since the integrity of the mitochondrial apparatus of cardiomyocytes is the basic link in maintaining the physiological morpho-functional balance of cardiomyocytes. At the same time, it is established that in the cell doxorubicin is predominantly accumulated in the mitochondria, which also makes emphasizes onto the prospects of studying this issue.

Purpose
Purpose of the study was to investigate the influence of AC mode of chemotherapy (adriamicin (doxorubicin) + cyclophosphomide) on the mitochondrial topoisomerases levels.

Methods
60 inbred mice of the C57BL/6J line with genotype a,H-2b were used. The experimental animals were divided into 2 groups: in the first group polychemotherapy in AC mode was applied; in the second group (placebo group) saline solution was used. Doxorubicin (Sigma Aldrich) was administered at a dose of 4 mg/kg and cyclophosphamid (Sigma Aldrich) at a dose of 2 mg/kg were administered intravenously. There were 4 courses conducted with the intervals of 21 days between them. The study results were recorded in 6 days after the last cycle of chemotherapy. The total duration of experiment was 90 days. The following types of topoisomerases have been studied: Top2β, Top3α, and Top1mt.

Results
The results of the first group showed a decrease in the Top2β level by 2.4±0.4%, Top3α - by 0.7±0.5, and Top1mt - by 49.5±11.7% (p=0.05). When analyzing the results of the second group no statistically significant changes were recorded.

Conclusion
The fact of AC mode of chemotherapy administered should be taken as a predictor of destabilization of the mitochondrial topoisomerases signaling, in particular of the Top1mt, which in turn, causes the development of mitochondrial dysfunction and results the energy imbalance in cardiomyocytes.

Funding Acknowledgement
Type of funding source: None
Severe preeclampsia is associated with postpartum diastolic dysfunction and non-dipping blood pressure profile pattern
Authors: Abdel Ghany M , Rashed M , Abbas A , Youssef A.M.R , Sayed M 
Published: November 2020

Abstract

Background
Left ventricular diastolic dysfunction and non-dipping profile, detected by ambulatory blood pressure monitoring (ABPM), are two features recorded to be associated with sustained hypertension. Both are predictors of an increased cardiovascular morbidity later in life. Complete normalization of blood pressure (BP) in preeclampsia is detected over a variable period of time.

Methods
A prospective cohort study was conducted in a tertiary university hospital including normotensive women with a history of preeclampsia in the current pregnancy enrolled within the first week postpartum. All cases were subjected to 24 h-ABPM and 2D trans-thoracic echocardiography three months post postpartum concomitantly with a clinical evaluation. Chi2-test was used to compare the qualitative data while student t-test was used to compare the quantitative data. Multivariate regression analysis was used for prediction of non-dippers and diastolic dysfunction in our cohort.

Results
Hundred twenty eight women were included in the study. Their mean age was 28.6±5.1 years and the mean basal BP was 123.1±6.4/74.6±5.9 mm Hg. Out of the studied women, 90 (70.3%) women were dippers and 38 (29.7%) women were non-dippers. It was noticed that diastolic dysfunction was presented in 28 (73.7%) of non-dippers while none of dippers had diastolic dysfunction. Women with severe preeclampsia had higher frequency of non-dipper (35.5% vs. 24.2%; P=0.02) and diastolic dysfunction (29% vs. 15%; P=0.01) in comparison to those women with mild preeclampsia. Severe preeclampsia and previous history of preeclampsia were significant predictors for non-dipping status (OR=1.1, 95% CI: 0.05–10.56 and 1.4, 95% CI: 0.30–4.26 respectively, R2 = 0.7; P&lt;0.001). They were also predictors for diastolic dysfunction in our studied population (OR = 1.6, 95% CI: 1.1–2.2 and 1.3, 95% CI: 1.2–2.2 respectively, R2 = 0.6; P&lt;0.05).

Conclusion
Women with a history of preeclampsia have the risk for developing cardiovascular events later in life. The severity and recurrence of preeclampsia were significant predictors for both non-dipping profile and diastolic dysfunction.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Orman Heart Hospital-Assiut University; Women Health Hospital-Assiut University
Cardiac surgery during pregnancy: what is the optimal timing of intervention? A meta-analysis of individual patient data
Authors: Van Steenbergen G , Tsang Q.H.Y , Kimmenade R.R.J , Van Der Heijden O.W.H , Vart P , Roos-Hesselink J.W , Li W.W.L , Verhagen A.F.T.M 
Published: November 2020

Abstract

Background
Cardiac disease can manifest or worsen during pregnancy and some cases urges cardiac surgery. According to current guidelines, the second trimester is supposed to be the optimal time frame. However, evidence for this recommendation is poor.

Objective
We evaluate whether an optimal period to undergo cardiac surgery during pregnancy can be identified, focusing on both maternal and foetal outcomes.

Methods
All studies published in Medline up to February 8th, 2018 on maternal and/or foetal outcome of cardiac surgery during pregnancy that included individual patient data were identified. Three groups were analysed: all identified patients (total population), patients who underwent caesarean section (CS) prior to cardiac surgery (subgroup A) and patients who underwent cardiac surgery with the foetus in utero (subgroup B). For the total population and subgroup B, logistic regression analysis was performed to find predictors of maternal and foetal outcome.

Results
We identified 142 studies including 328 patients of which 114 underwent CS prior to cardiac surgery (subgroup A). Maternal mortality in the total population was 5.2% and did not differ significantly among trimester (p=0.634). Foetal mortality in the total population was lowest in the third trimester (9.4%, p&lt;0.01) and CS prior to surgery significantly reduced risk of foetal mortality in a multivariate model (OR 0.09, CI 0.02–0.35). Subgroup analysis showed foetal mortality of 7.0% in subgroup A and 33.6% in subgroup B (p&lt;0.01). Trimester was not identified as a significant predictor for foetal and/or maternal mortality in subgroup B. See table 1.

Conclusion
Maternal mortality of cardiac surgery during pregnancy is not significantly influenced by trimester. Foetal mortality after maternal cardiac surgery is very high. When the fetus is viable, CS prior to cardiac surgery should be considered in the third trimester. If not feasible or safe to postpone surgery, trimester stage should not delay cardiac surgery.

Funding Acknowledgement
Type of funding source: None
Protease inhibitor-contaning antiretroviral therapy effects on QT interval and heart rate: a cross-sectional study
Authors: Rodriguez Szaszdi D , Bogran Castro D , Alvarado Sosa J 
Published: November 2020

Abstract

Background
HIV has been associated with QT prolongation and it is believed this is from drug interaction as well as HIV infection. In vitro studies have showed that protease inhibitors block potassium channel HERG, suggesting that these drugs can cause drug-induced QT prolongation. Few case-reports have showed that protease inhibitors can cause drug-induced bradycardia, but data is still limited.

Objective
To describe the correlation between HIV infection and the duration of QT interval and to evaluate the effects that protease inhibitors-containing antiretroviral regime have on the duration of QT interval and cardiac frequency.

Methods
A cross-sectional study was made. Participants were assigned to 3 groups: HIV positive with antiretroviral therapy which included protease inhibitors (HIV+ with treatment), treatment-naïve HIV positive and HIV negative. None of the participants had past medical history of cardiovascular disease or use of known QT prolonging medication. 12-lead ECG were made to all participants. QT interval and cardiac frequency were measured to be compared between the 3 groups and the results were analyzed by the statistical test ANOVA.

Results
A total of 213 participants were enrolled, 84 in the HIV+ with treatment, 45 in the HIV+ treatment-naïve, and 84 HIV-. 63% of the participants were males. The treatment-naïve HIV+ group only had 5 female participants. This study did not find a relation between HIV infection or protease inhibitor use and an increase in the duration of QT interval in males. For females, this study found an association between HIV infection and longer QT interval duration, as seen in the mean of each group: 442.8 ms for treatment-naïve HIV+ group, 422.42 ms for protease inhibitor HIV+ with treatment group and 420.34 ms HIV- group. It was found that the use of antiretroviral regime with protease inhibitor was associated with a decrease in cardiac frequency, as seen in each group's cardiac frequencies: HIV+ with treatment group: 63.34 bpm, treatment-naïve HIV positive: 79.77 bpm and control group: 69.3 bpm.

Conclusion
We did not find correlation between HIV infection, the use of protease inhibitor-containing antiretroviral regime and QT interval prolongation in males, as opposed to females, where it was shown that QT interval duration is longer in the HIV+ treatment-naïve group. It was also observed that the use of protease inhibitor-containing antiretroviral regime was associated with a decrease in cardiac frequency.

Funding Acknowledgement
Type of funding source: None
HIV may indirectly accelerate coronary artery disease through enhancing the effects of conventional and non-conventional cardiovascular risk factors
Authors: Kolossvary M , Fishman E.K , Gerstenblith G , Bluemke D.A , Mandler R.N , Kickler T.S , Bazr S , Chen S , Lai S , Lai H 
Published: November 2020

Abstract

Background/Introduction
Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated.

Purpose
In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA).

Methods
Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3 years). Agatston-score, number of coronary plaques, segment stenosis score were calculated, and we also segmented the coronary plaques to enumerate total, noncalcified (−100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CCTA markers of CAD.

Results
In univariate analysis, there was no significant difference in CAD characteristics between HIV-infected and -uninfected, neither at baseline nor at follow-up (p&gt;0.05 for all). Furthermore, there was no significant difference in annual progression rates between the two groups (p&gt;0.05 for all). By multivariate analysis, HIV was not associated with any CAD parameter (p&gt;0.05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p&lt;0.05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p&lt;0.05). These associations were only present among HIV-infected individuals.

Conclusion(s)
Instead of directly worsening CAD, HIV may promote CAD through increased susceptibility to conventional and nonconventional cardiovascular risk factors. Therefore, aggressive management of both conventional and nonconventional cardiovascular risk factors is needed to reduce cardiovascular burden of HIV-infection.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Institute on Drug Abuse
Visit-to-visit systolic blood pressure variability associates with vascular thrombosis in hemodialysis patients
Authors: Wu C.C , Lin P.S , Hsieh M.Y , Chen T.Y , Lin T.T , Chuang S.Y 
Published: November 2020

Abstract

Background
Blood pressure variability (BPV) is an independent risk factor for cardiovascular events and death in general population. Hemodialysis patients have higher BPV and higher vascular events than general population. However, the impact of BPV on vascular events of hemodialysis patients is not clear.

Purpose
To determine the association of BPV with vascular outcomes in patients on maintenance hemodialysis.

Method
In this prospective multi-center study, we enrolled 927 maintenance hemodialysis patients from Jan, 2017 to Dec, 2017. We used the coefficient of variation (CV) and the variance independent of mean (VIM) of predialysis systolic blood pressure (SBP) derived from the first 3 months (36 dialysis sessions) after enrollment as the metrics of BPV. Patients were prospectively followed at 3-month interval. Outcomes included death, systemic vascular thrombosis (nonfatal myocardial infarction, ischemic stroke, and acute limb ischemia), and dialysis vascular access thrombosis.

Results
In all, 707 subjects with at least 20 measurements were included in the analysis. Patients' mean age was 66 years and 50% of patients were male. Baseline factors associated higher BPV included diabetes, high co-morbidity scores, low albumin, high systolic and diastolic blood pressure. The mean pre-dialysis SBP CV was 10.9% and VIM was 28.9%. The median follow-up duration was 2.5 years, during which 103 deaths, 81 systemic vascular thrombosis, and 155 dialysis access thrombosis occurred. In unadjusted model, we found that the highest BPV tertile had a 52% increased risk of vascular thrombosis than the lowest BPV tertile (HR=1.52, 95% CI 1.23–1.86, P&lt;0.001). After multivariable adjustment (including age, diabetes, co-morbidity score, albumin, baseline systolic and diastolic BP), this association remained statistically significant (HR=1.47, 95% CI=1.18–1.84, P=0.001). Systolic BPV was associated with either systemic vascular thrombosis (HR=1.44, 95% CI=1.08–1.93, P=0.01) or dialysis vascular access thrombosis (HR=1.55, 95% CI=1.16–1.82, P=0.001).

Conclusion
In the cohort of patients on maintenance hemodialysis, high pre-dialysis systolic BPV was associated a higher risk of vascular thrombosis events, both for systemic vascular thrombosis and dialysis vascular access thrombosis.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): National Taiwan University Hsinchu Branch
Patterns and trends of idarucizumab use in an Italian region: a probabilistic record-linkage approach in a real-life setting
Authors: Lombardi N , Brilli V , Crescioli G , Bettiol A , Ippazio C.A , Mazzaglia G , Fumagalli S , Mannaioni G , Vannacci A , Gini R 
Published: November 2020

Abstract

Background
Idarucizumab is a specific reversal agent for dabigatran, a direct oral anticoagulant. In 2015, idarucizumab was approved in Europe to quickly restore coagulation and it is currently subject to additional safety monitoring. The drug is administered only during inpatient or emergency care: in such settings, its use is poorly captured by most real-world databases.

Purpose
To retrieve individual level information on idarucizumab use from an Italian record-linkage claims database in order to describe main characteristics of users.

Methods
Italy has a regional-based, universal coverage healthcare system. Healthcare delivered to each inhabitant of Tuscany, an Italian region, is registered in a record-linkage claims database (RLCD). This information can be traced at individual level using an encrypted identification code, except in the case of medicines administered in Inpatients or Emergency Care (IEC), where only date and ward of administration are recorded. All person-years (PYs) exposed to dabigatran from January 2015 to December 2018 were calculated from RLCD, using defined daily doses (DDDs) to estimate duration of each recorded dispensation. Idarucizumab use during the study period was identified from IEC, and incidence rate was calculated over PYs of dabigatran use. To identify subjects treated with idarucizumab, emergency admissions and hospital discharge records were probabilistically linked to dabigatran users, matching date and ward of admission as retrieved from RLCD. A further selection was made by a manual check of the diagnoses compatible with the indications of use of idarucizumab. Linked users were described in terms of indication and followed-up for 30 days to assess mortality.

Results
During the study period, 26,821 PYs of dabigatran use were observed, and 112 administrations of idarucizumab were recorded, corresponding to 4.2 (95% CI: 3,4–5,0) per 1,000 PYs. Overall, 103 idarucizumab administrations (92.0%) were linked to at least one patient, while 50 (44.6%) were uniquely linked to 47 patients. Most of them were men (55.3%), aged ≥80 years (68.1%). Indications were emergency surgical procedures and life-threatening bleeding in 17 (36.1%) and in 30 subjects (63.9%), respectively. Overall, 30-days mortality was 17.0% (N=8).

Conclusions
This analysis demonstrates the potential of the Tuscany database in retrieving patient-level information on idarucizumab use and sets the stage for post-marketing surveillance on its safety profile in a real-life setting.

Funding Acknowledgement
Type of funding source: None