bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab, Ipilimumab and Nivolumab reduces cardiac pAMPK and IL-10, increases vascular NF-kB expression and levels of IL-1b, IL-2 and IL-6 in myocardial tissue
Authors: Maurea N , De Lorenzo C , Passariello M , Iovine M , Buccolo S , Di Mauro A , Cipullo C , Paccone A , Maurea F , Caronna A , Quagliariello V 
Published: October 2022

Abstract

Background
Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality.

Purpose
We analyzed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.

Methods
C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. pAMPK expression and vascular p65/NF-kB was analyzed through Immunohistochemistry. Cardiac levels of IL-1α, IL-1β, IL-2, IL-6 and IL-10 were quantified through ELISA method

Results
In preclinical models, all ICIs increased p65/NF-kB expression in vascular endothelial cells of mice compared to saline group. IHC analysis indicates that ICIs reduced pAMPK expression in myocardial cells. Notably, tissue levels of IL-1α, IL-1β, IL-2, IL-6 were strongly increased in ICIs group vs saline (p&lt;0.05 vs saline). On the other hand, levels of the anti-inflammatory cytokine IL-10 were strongly reduced (overall reduction of 43.3–54.5% vs saline)

Conclusion
In preclinical models, a short treatment with ICIs is sufficient to confer a pro-inflammatory phenotype in the heart of mice. Furthermore, reductions in pAMPK indicate the inhibition of mitochondrial metabolism after ICIs. Furthermore ICIs induce chemokines involved in fibrosis, myocarditis and vascultitis. These results could indicate new therapeutic candidates aimed to prevent myocardial and vascular damages in cancer patients treated with ICIs.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute
Berberine associated to SGLT2i Dapagliflozin synergistically reduces cardiac cell apoptosis during exposure to Trastuzumab through reduction of AGEs and IL-6 and induction of pAMPK
Authors: Maurea N , Buccolo S , Iovine M , Maurea C , Paccone A , Quagliariello V 
Published: October 2022

Abstract

Background
Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Recent preclinical systematic review indicated that Berberine significantly reduces myocardial infarct size and the incidence of ventricular arrhythmia, improves cardiac function, ameliorates myocardial apoptosis.

Purpose
To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER-2 blocking agent-induced cardiotoxicity

Methods
Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes-B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL-6 was performed through ELISA method.

Results
Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p&lt;0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL-6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group).

Conclusion
Berberine and Dapagliflozin exerts significant cardioprotective effects in cardiac cells exposed to the HER2-bloking agent Trastuzumab. Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute
Dose-dependency of diclofenac's cardiovascular risks: a series of nationwide emulated trials
Authors: Schmidt M , Arendt-Nielsen L , Hauge E M , Soerensen H T , Pedersen L 
Published: October 2022

Abstract

Background
The dose dependency of the adverse effects of diclofenac remains poorly understood.

Purpose
To examine the dose-related cardiovascular risks associated with diclofenac initiation

Methods
We used Danish nationwide health registries (1999–2018) to conduct a series of emulated trials (n=285). Eligible adults had no recent NSAID fillings, contraindications, or conditions with low adherence. Individuals eligible for inclusion were ≥18 years with (1) ≥90 days continuous prescription records prior to diclofenac initiation (baseline); (2) no NSAID prescriptions ≤90 days before enrollment, and (3) no exclusion criteria. Exclusion criteria reflected likelihood of low adherence to treatment (dementia, schizophrenia, or antipsychotic drug use) and labeled contraindications (ulcer disease/anti-ulcer drugs, gastrointestinal bleeding, inflammatory bowel disease, thrombocytopenia, or heart failure). Initiators of diclofenac were compared to healthcare-seeking non-initiators, but also head-to-head for initiators of high (≥75 mg pills as proxy for ≥150 mg/daily) vs. low dose (≤50 mg pills as proxy for &lt;150 mg/daily). Cox proportional-hazards regression was used to compute the intention-to-treat hazard ratio, as measure of the incidence rate ratio (IRR), of major adverse cardiac and cerebrovascular events (MACCE) within 30 days from initiation.

Results
Among 3,177,484 diclofenac initiatiors, 31% used high and 69% used low dose. Compared with non-initiators, diclofenac initiatiors had a 70% increased rate for MACCE (IRR 1.70, 95% CI: 1.55–1.86), reflecting for the individual MACCE components an increased IRRs of 1.66 (95% CI: 1.54–1.79) for myocardial infaction, 1.32 (1.20–1.45) for ischemic stroke, and 1.69 (1.54–1.86) for cardiac death. The effect for MACCE did not differ between initiators of high (IRR 1.73, 95% CI: 1.51–1.97) and low dose (IRR 1.68, 95% CI: 1.52–1.86) (Figure 1). When comparing high and low dose diclofenac head-to-head, we found no meaningful difference in the IRR for MACCE (1.03, 95% CI: 0.89–1.19), MI (0.99, 0.87–1.11), ischemic stroke (0.95, 0.81–1.11) or cardiac death (1.04, 0.90–1.21) (Figure 2).

Conclusion
Initiation of low- and high-dose diclofenac was associated with a consistent and comparable increase in cardiovascular risk.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation
A blueprint for the continuation of comprehensive cardiac rehabilitation during the COVID-19 pandemic. An Australian single hospital experience
Authors: Zecchin R , Dickson C , Hungerford J , Leow J , Lindsay G , Mander R , Saliba I , Denniss A R 
Published: October 2022

Abstract

Background
The COVID-19 pandemic has disrupted cardiac rehabilitation (CR) around the world with an estimated 50–75% of CR programmes discontinuing or reducing services. Alternative models such as TeleHealth have been encouraged and adopted in place of face to face (F2F) CR. There is a paucity of published data on the continuation of F2F CR during the pandemic.

Methods
A retrospective database audit examined the CR participation rates at an Australian quaternary public hospital during the pre-COVID (2018/2019) and in-COVID (2020/2021) periods. Socio-demographic status, diagnosis at CR entry, CR modalities, and outcome measures (wait times, completion rates) were analysed.

Results
There were no COVID-19 cases or cross infections occurring in CR during the in-COVID period. An audit of 1623 consecutive patients who attended our CR programme (pre-COVID n=760: in-COVID n=863) were included in this study. No significant differences were observed in age, male sex, CR wait times and completion rates between the two groups. Participation rates of patients diagnosed with heart failure (CCF) increased (p=0.02) and those who entered CR after elective PCI decreased (p=0.03) during the in-Covid period in comparison with the pre-COVID period. Total F2F CR was maintained in the in-COVID period compared to the pre-COVID period (85%: 89%, p=not significant (NS)). A significant increase in F2F utilising home walking (p&lt;0.0001) and a decrease in F2F utilising supervised exercise (p&lt;0.0001) was seen. TeleHealth, introduced during the in-COVID period, only contributed to 6% of the total CR participation. More detailed results of this study are presented in Table 1 below.

Conclusions
During the COVID-19 pandemic our CR programme adhered to state health orders, recorded zero transmissions, maintained face to face services, and increased CR uptake only partially due to the introduction of TeleHealth. Our blueprint for the successful continuation of CR during COVID involves having expert nursing management, medical CR champions, dedicated CR gym, and well-established, flexible patient-centric programme modalities.

Funding Acknowledgement
Type of funding sources: None.
Cognitive impairment and low health literacy are associated with poor health outcomes in patients with heart failure
Authors: Wu J , Moser D 
Published: October 2022

Abstract

Background
Cognitive impairment and low health literacy are prevalent in patients with heart failure (HF). Low health literacy is associated with poor health outcomes, such as frequent re-hospitalizations and increased mortality. Little is known about the relationships among cognitive impairment, health literacy, and health outcomes (HF rehospitalization and cardiac death).

Objective
To explore the associations among cognitive impairment, health literacy, and cardiac event-free survival in patients with HF.

Methods
This was a longitudinal study of 614 rural patients with HF (male 59%, age 66±13 NYHA class III/IV: 35%). Cognitive function was measured using the Mini-Cog test. Health literacy was measured by the Short Test of Functional Health Literacy in Adults. HF hospitalizations and cardiac mortality were followed at least 2 years and obtained by patient interview, medical record review, and death certificate review. Chi-squares, t-tests, ANOVA, Kaplan-Meier with log rank tests, logistic and Cox regressions were used for data analysis.

Results
Two hundred and seven patients (34%) had cognitive impairment. Compared to those without cognitive impairment, patients with cognitive impairment were 2.77 times more likely to have low health literacy (P&lt;0.001). Patients were divided into 4 groups based on cognitive impairment or not and adequate/low health literacy: (1) No cognitive impairment with adequate health literacy; (2) cognitive impairment with adequate health literacy; (3) no cognitive impairment with low health literacy; and (4) cognitive impairment with low health literacy. Both cognitive impairment and health literacy independently predicted cardiac event-free survival. Cardiac event-free survival was worst in those with both cognitive impairment and low health literacy compared to patients in any of the other three groups. Patients with cognitive impairment and low health literacy had 3.5 times higher risk of a cardiac event compared to those without cognitive impairment or low health literacy (P&lt;0.001, Figure). Age, income, angiotensin converting enzyme inhibitor use, beta-blocker use, New York Heart Association functional class, left ventricular ejection fraction, BNP level were significantly different among the four cognitive and literacy groups.

Conclusion
Patients with cognitive impairment with low health literacy were at high risk of experiencing a cardiac event. Interventions need to be developed to target high risk patients with cognitive impairment and low health literacy, such as older, low-income patients, to alleviate poor outcomes in patients with HF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH/NHLBI
Patients and healthcare professionals views on injectables for cardiovascular disease
Authors: Lee G , Durante A , Vellone E , Dellafiore F , Cagginelli G , Khan M , Baker E E , Khatib R 
Published: October 2022

Abstract

Introduction
Injectable medicines are increasingly used to manage risk factors for cardiovascular (CV) events, such as PCSK-9 inhibitors in dyslipidaemia and GLP-1 agonists in diabetes. However, there is a paucity of data around the administrative and clinical practicalities when using these injectables, and limited information on patient and healthcare professionals' perceptions.

Purpose
To identify the facilitators and barriers on the use of injectable therapies with CV benefits by undertaking interviews with patients, caregivers and healthcare professionals (HCPs).

Methods
Interviews were conducted via telephone and using MS Teams due to Covid-19 restrictions in the United Kingdom (London and Leeds) and Italy (Rome and Milan) in 2021. Coding was undertaken using NVivo and thematic analysis performed.

Results
A total of 56 patients were interviewed: 30 in the U.K. (mean age 66 yrs, 60% male) and 26 patients in Italy (mean age 63 yrs, 80% male) and 11 caregivers (mean age 59 yrs, 73% female). A total of 38 HCPs were interviewed, 19 in each country and composed of physicians (n=18), pharmacists (n=10), nurses (n=9) and pharmacy technician (n=1). Three distinct themes were identified: (i) Organisational and governance issues - relating to prescribing restrictions and availability of the drugs locally (PCSK9i are initiated and supplied from hospitals) and lack of communication between hospital and primary care setting; (ii) Clinical issues around HCPs' skills and experience - including: lack of experience with these injectables, lack of time to provide education to patients and caregivers, therapeutic inertia (HCPs not adopting a change in practice despite the evidence or due to bureaucratic restrictions) as well as lack of knowledge on long-term effects, and finally (iii) Patient-related issues - relating to behaviours and beliefs such as reluctance about using injectable therapies, and lack of education about these injectables in terms of indications/clinical benefits for use. Despite some differences in the prescribing of these injectables in the two countries, the analysis captured similar facilitators and barriers. Facilitators included prior use of injectables (e.g. insulin), and the ability to reach a clinical target of lower cholesterol by having just a “one shot”. HCPs stated that access to rapid pathology tests would aid uptake of injectables with CV benefit as well as having educational tools on these injectables in practice.

Conclusion
This qualitative study identified barriers to initiation, continuation, and adherence with injectable therapies with CV benefits but also highlighted areas where changes can be made especially around education and support for patients and HCPs.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): ACNAP education grant. Sponsored by Amgem and Novo Nordisk
Changes in self-care maintenance during quarantine in patients with heart failure
Authors: Klompstra L , Almenar L , Deka P , Munoz-Gomez E , Lopez-Vilella R , Pathak D , Westas M , Marques-Sule E 
Published: October 2022

Abstract

Background
Patients with heart failure (HF) experience challenges in self-care that contribute to poor quality of life and high health care utilization. The COVID-19 pandemic required HF patients, especially living in countries with strict lockdowns and quarantines, to change their lifestyle including health promoting behaviors.

Purpose
To assess changes in self-care maintenance in patients with HF changed during quarantine compared to before quarantine. We hypothesized that the self-care maintenance behavior physical activity was most effected during quarantine.

Method
This is a cross-sectional survey study. From the medical chart, patients' disease severity (NYHA-class), ejection fraction and comorbidities were collected. Self-care maintenance was assessed using subscale Self-Care of Heart Failure Index 6.2. The total score ranges from 0–100, where 70 or higher is seen as having good self-care maintenance. With all the questions in the self-care maintenance scale a question was added: Did this change due to the COVID-19 pandemic? Patients could answer yes or no. When patients answered yes, they were asked the elaborate. Patients self-reported physical activity, before and during the pandemic, using the International Physical Activity Questionnaire (short form). Descriptive analyses were used for self-care maintenance, content analysis was applied for the qualitative data. Paired sample t-test were performed to assess the change in the total physical activity.

Results
In total, 120 patients with HF were included in this study (mean age was 79±13, 39% female, 78% NYHA-class I/II). Patients had a mean self-care maintenance of 32 (±6). No participant had good self-care maintenance (score of 70 or higher). Patients were non-adherent to regular physical activity (77%, n=92), keeping weight down (74%, n=89) and weighing themselves (66%, n=79) during quarantine (Figure). Behaviors which changed the most included keeping medical appointments (81%) and regular exercise (82%). Significantly higher levels of physically active was noticed before quarantine (776 Mets-minutes) compared to during quarantine (106 Mets-minutes) (p&lt;0.01). The change in self-care maintenance was explained by change in motivation and self-confidence. Because of the pandemic and the quarantine, patients reported not being able to rely on health care and their usual social support system. Patients tried to create new habits when trying to maintain their self-care.

Conclusion
Patients with HF reported experiencing low self-care maintenance during quarantine due to not being able to go to medical appointments and decrease in physical activity. Public health policies during crisis events such as a pandemic should strive to provide support in coping with these changes and offer alternative ways of maintaining their self-care maintenance, especially with physical activity.

Funding Acknowledgement
Type of funding sources: None.
A service evaluation of patch technology compared with traditional holter monitoring in a stroke pathway
Authors: Orava S , Chauhan M , Stain N 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) is a known risk factor for embolic stroke. Establishing a diagnosis of AF will guide clinical decision making and help with downstream secondary stroke prevention. Patch technology is increasingly used for long-term cardiac monitoring for arrhythmia detection, as healthcare organisations look for new innovative ways to streamline service delivery. We were selected as a host site to evaluate the service and patient benefits of Zio XT in AF detection for cryptogenic stroke, as part a Artificial Intelligence Award.

Purpose
To evaluate the service and patient benefits of patch technology versus traditional Holter in a Stroke / TIA pathway.

Methods
The Zio XT data were collected between March and December 2021. A total of 778 patients were included. We only selected patients who were referred for a long-term ambulatory monitoring following a recent diagnosis of stroke or transient ischaemic attack (TIA) of an unknown cause (cryptogenic). The stroke pathway operates across three sites and all were included. We undertook a retrospective analysis of our previous pathway using Holter monitoring and sampled 100 stroke / TIA patients who underwent 24–72 hours of monitoring between January to June 2019. In order to obtain the requisite data a variety of sources were scrutinised: referral letters, test reports, patient medical records, internal clinical systems and third-provider platforms.

Results
The comparison of the ECG technologies showed the Zio XT used less staff time. We found a 50% reduction in-clinic monitor fitting when compared with Holter. Zio XT were all analysed by the provider staff resulting in significant savings in service resource time for analysis. The Zio XT had a faster test turnaround time (referral to report available), 19 days (inclusive of 14 days wear time) for Zio compared with 60 days for Holters. The rapid Zio turnaround led to a 27.5% reduction in repeat clinic appointments, due to results being unavailable for the consultation (table 1). Zio XT also had fewer repeat testing due to inconclusive results, 1% for Zio versus 16% for Holter. AF yield did not vary significantly between technologies, 3% yield for both Holter and Zio, which could be due to the young mean age of the stroke/ TIA the patient cohort: 63.8 years for Holter versus 62.9 years for Zio XT.

Conclusion
Introducing new ECG technologies such as Zio XT could increase outpatient and diagnostic capacity due to patches being more readily available than Holters, reduced reliance on clinical staff for fitting and analysis as well as fewer repeat clinic appointments. Overall, access to rapid long term cardiac monitoring has benefits over traditional Holter monitoring for TIA/stroke patients and service delivery.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): AI award from the Accelerated Access Collaborative (ACC) in partnership with NHSX and National Institute for Health Research