Aims\nLeadless cardiac pacing has recently been proposed as alternative to conventional right ventricular (RV) pacing. With this approach, devices are directly screwed or fixed with tines in the RV wall, but the possible consequences on RV and tricuspid valve (TV) structure and function remain unknown. We thus conducted a study to evaluate this potential impact in chronically implanted patients.\n\n\nMethods and results\nRepeated echocardiographic studies were performed prior to implantation, at discharge, and 2 months thereafter on all consecutive patients implanted with a leadless pacemaker at our centre between October 2014 and end-December 2015. Whenever possible, patients were evaluated in non-paced rhythm. Anatomical and functional parameters of RV, TV, and left cardiac structures were assessed. Overall, 23 patients (12 females, aged 85.2 ± 6.3 years) were included, with 14 implanted using Nanostim™ (Saint Jude Medical) and 9 with Micra™ (Medtronic). Indications for pacing were paroxysmal atrio-ventricular block in 12 patients, intermittent sinus bradycardia in 5, unexplained syncope in 3, and atrial fibrillation with slow ventricular rate in the remaining 3. The pacing percentage was 34 ± 42% at the last visit. Most devices were implanted in the septo-apical or mid-septal region. There were no significant changes in echocardiographic parameters observed. One patient developed significantly increased TV regurgitation, without abnormal leaflet motion or TV annulus size changes, suggesting it to be due to RV pressure changes.\n\n\nConclusion\nIn patients chronically implanted with leadless pacemakers, there were no significant changes in heart structure and function observed, especially concerning the RV and TV.

Right ventricular and tricuspid valve function in patients chronically implanted with leadless pacemakers

Prostate cancer (PC) is the third most frequently diagnosed cancer worldwide and the second most frequent in men. Several risk factors can contribute to the development of PC, and those include age, family history, and specific genetic mutations. So far, drug testing in PC, as well as in cancer research in general, has been performed on 2D cell cultures. This is mainly because of the vast benefits these models provide, including simplicity and cost effectiveness. However, it is now known that these models are exposed to much higher stiffness; lose physiological extracellular matrix on artificial plastic surfaces; and show changes in differentiation, polarization, and cell–cell communication. This leads to the loss of crucial cellular signaling pathways and changes in cell responses to stimuli when compared to in vivo conditions. Here, we emphasize the importance of a diverse collection of 3D PC models and their benefits over 2D models in drug discovery and screening from the studies done so far, outlining their benefits and limitations. We highlight the differences between the diverse types of 3D models, with the focus on tumor–stroma interactions, cell populations, and extracellular matrix composition, and we summarize various standard and novel therapies tested on 3D models of PC for the purpose of raising awareness of the possibilities for a personalized approach in PC therapy.

https://www.mdpi.com/1422-0067/24/6/5293/pdf?version=1678420331

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Relationship between cigarette use and prostate cancer risk: what do we know and what should we do?

Simple Summary As lifestyle intervention has come to the fore for cancer prevention, the causal effect of lifestyle behaviors on prostate cancer remains to be elucidated. No comparison across different ethnicities has been conducted previously. In this study, we used a novel instrumental variable methodology, namely, Mendelian randomization analysis, to explore the associations between a wide range of behavioral factors and prostate cancer in both Europeans and East Asians. The results of this study showed that lifetime tobacco smoking was positively related to an increased prostate cancer risk in Europeans. In East Asians, alcohol consumption and delayed sexual initiation were risk factors, while vegetable intake was a protective factor for prostate cancer. These findings largely broaden the evidence base for the spectrum of risk factors for prostate cancer, and provide insights into the priority of behavioral interventions for high-risk groups in different population settings. Abstract Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. Methods: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). Results: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09–3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01–1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00–1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88–0.96, p = 0.001) was a protective factor for PCa. Conclusions: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.

/pdf/causal-effects-of-modifiable-behaviors-on-prostate-cancer-in-1erfevws.pdf

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study

2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review.

Modifiable risk factors for prostate cancer in low- and lower-middle-income countries: a systematic review and meta-analysis

Beyond the Wires: A Case of Leadless Pacemaker-Mediated Tricuspid Regurgitation.

605 Validation Of Aortic Valve Computed Tomography Calcium Quantification In Contrast Computed Tomography

BACKGROUND
Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including the adverse cardiometabolic effects of androgen deprivation therapy for prostate cancer, make cardiovascular disease an frequent and important co-morbidity in patients with a genitourinary malignancy. Complex cardiovascular disease can pose significant challenges in the management of these patients given the uncertainties related to the best approach to reconcile ischemic and bleeding risks, and the role of invasive cardiovascular interventions in individuals with advanced cancer. In this review, we discuss the current evidence that informs decision-making in this clinical context.

The Cardiologist's Role in the Management of Patients with a Genitourinary Cancer.

INTRODUCTION
Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity.


MATERIALS AND METHODS
We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration.


RESULTS
Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function.


CONCLUSIONS
Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up.

Filipe Cirne

Papers

Modifiable risk factors for prostate cancer in low- and lower-middle-income countries: a systematic review and meta-analysis

Beyond the Wires: A Case of Leadless Pacemaker-Mediated Tricuspid Regurgitation.

605 Validation Of Aortic Valve Computed Tomography Calcium Quantification In Contrast Computed Tomography

The Cardiologist's Role in the Management of Patients with a Genitourinary Cancer.

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.