Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium

Purpose: Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients. Methods: Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters. Results: Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively). Conclusion: The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.</p

“Shake It Baby, Shake It”: Media Preferences, Sexual Attitudes and Gender Stereotypes Among Adolescents

In this study exposure to and preferences for three important youth media (TV, music styles/music TV, internet) were examined in relation to adolescents’ permissive sexual attitudes and gender stereotypes (i.e., views of men as sex-driven and tough, and of women as sex objects). Multivariate structural analysis of data from a school-based sample of 480 13 to 16-year-old Dutch students revealed that preferences, rather than exposure were associated with attitudes and stereotypes. For both girls and boys, preferences for hip-hop and hard-house music were associated positively with gender stereotypes and preference for classical music was negatively associated with gender stereotypes. Particularly for boys, using internet to find explicit sexual content emerged as a powerful indicator of all attitudes and stereotypes

A visual analytics approach for effective radon risk perception in the IoT era

Radon gas is one of the most relevant indoor pollutants in areas of slaty and granitic soils, and is considered by the World Health Organization (WHO) as the second-largest risk factor associated with lung cancer. In the IoT era, active radon detectors are becoming affordable and ubiquitous, and in the near future, data gathered by these IoT devices will be streamed and analyzed by cloud-based systems in order to perform the so-called mitigation actions. However, a poor radon risk communication, independently of the technologies and the data analytics adopted, can lead to a misperception of radon risk, and therefore, fail to produce the wanted risk reduction among the population. In this work we propose a visual analytics approach that can be used for effective radon risk perception in the IoT era. The proposed approach takes advantage of specific space-time clustering of time-series data and uses a simple color-based scale for radon risk assessment, specifically designed to aggregate, not only the legislation in force but also the WHO reference level, by means of a visual analytics approach. The proposed methodology is evaluated using real time-series radon data obtained during a long-term period of 7 months.2411-78B2-7CDB | Pedro Miguel MoreiraN/

Prevention and rehabilitation - Three life-years gained from smoking cessation after coronary artery bypass surgery: A 30-year follow-up study

Background Previous studies have shown that smoking cessation after a cardiac event reduces the risk of subsequent mortality in patients, but the effect of smoking cessation in terms of prolonged life-years is not yet known. Methods We analyzed the 30-year clinical outcome of the first 1,041 consecutive patients (age at operation 51 years, 92% male) who successfully underwent isolated venous coronary artery bypass surgery between 1971 and 1980. All 55 1 smokers (53%) were included in this study. Of these, 43% stopped smoking throughout the first year whereas 57% persisted smoking. Results The median follow-up was 29 years (range 26-36 years). The cumulative 10-, 20-, and 30-year survival rates were 88%, 49%, and 19%, respectively, in the group of patients who quit smoking, and only 77%, 36%, and 11 %, respectively, in the persistent smokers (P <.0001). After adjusting for all baseline characteristics, smoking cessation remained an independent predictor Of lower mortality (hazard ratio 0.60, 95% CI 0.48-0.72). We were able to assess the exact life expectancy by calculating the area under the Kaplan-Meier curves. Life expectancy in the quitters was 20.0 years and 17.0 years in the persistent smokers (P < .0001). Conclusions Using 30-year follow-up data, we estimated that self-reported smoking cessation after coronary artery bypass surgery was associated with a life expectancy gain of 3 years. Smoking cessation turned out to have a greater effect on reducing the risk of mortality than the effect of any other intervention or treatment

Ratio of Intratumoral Macrophage Phenotypes Is a Prognostic Factor in Epithelioid Malignant Pleural Mesothelioma

Hypothesis: The tumor micro-environment and especially the different macrophage phenotypes appear to be of great influence on the behavior of multiple tumor types. M1 skewed macrophages possess anti-tumoral capacities, while the M2 polarized macrophages have pro-tumoral capacities. We analyzed if the macrophage count and the M2 to total macrophage ratio is a discriminative marker for outcome after surgery in malignant pleural mesothelioma (MPM) and studied the prognostic value of these immunological cells. Methods: 8 MPM patients who received induction chemotherapy and surgical treatment were matched on age, sex, tumor histology, TNM stage and EORTC score with 8 patients who received chemotherapy only. CD8 positive T-cells and the total macrophage count, using the CD68 pan-macrophage marker, and CD163 positive M2 macrophage count were determined in tumor specimens prior to treatment. Results: The number of CD68 and CD163 cells was comparable between the surgery and the non-surgery group, and was not related to overall survival (OS) in both the surgery and non-surgery group. However, the CD163/CD68 ratio did correlate with OS in both in the total patient group (Pearson r-0.72, p < 0.05). No correlation between the number of CD8 cells and prognosis was found. Conclusions: The total number of macrophages in tumor tissue did not correlate with OS in both groups, however, the CD163/CD68 ratio correlates with OS in the total patient group. Our data revealed that the CD163/CD68 ratio is a potential prognostic marker in epithelioid mesothelioma patients independent of treatment but cannot be used as a predictive marker for outcome after surgery

Optimization of intra-operative electrophysiological localization of the ligament of Marshall

Background: The ligament of Marshall (LOM) may play a role in the pathophysiology of several tachyarrhythmias and accurate electrophysiological localization of this structure is crucial for effective ablation therapy. This study therefore quantifies electrophysiological properties of the LOM, and identifies which electrogram (EGM) recording (uni- or bipolar) and processing technologies [local activation time (LAT) and/or voltage mapping] are most suitable for accurate localization of the LOM. Methods: The LOM was electrophysiologically identified in 19 patients (mean age 66 ± 14 years; 12 male) undergoing elective cardiac surgery using intra-operative high-density epicardial mapping, to quantify and visualize EGM features during sinus rhythm. Results: Only a third of LOM potentials that were visualized using unipolar EGMs, were still visible in bipolar activation maps. Unipolar LOM potentials had lower voltages (P50: LOM: 1.51 (0.42–4.29) mV vs. left atrium (LA): 8.34 (1.50–17.91) mV, p < 0.001), less steep slopes (P50: LOM: –0.48 (–1.96 to –0.17) V/s vs. LA: –1.24 (–2.59 to –0.21) V/s, p < 0.001), and prolonged activation duration (LOM: 20 (7.5–30.5) ms vs. LA: 16.5 (6–28) ms, p = 0.008) compared to LA potentials. Likewise, bipolar LOM voltages were also smaller (P50: LOM: 1.54 (0.48–3.28) mV vs. LA: 3.12 (0.50–7.19) mV, p < 0.001). Conclusion: The LOM was most accurately localized in activation and voltage maps by using unipolar EGMs with annotation of primary deflections in case of single potentials and secondary deflections in case of double or fractionated potentials

Normothermic Ex Situ Heart Perfusion with the Organ Care System for Cardiac Transplantation: A Meta-analysis

Background. Heart transplantation (HTx) is, at present, the most effective therapy for end-stage heart failure patients; however, the number of patients on the waiting list is rising globally, further increasing the gap between demand and supply of donors for HTx. First studies using the Organ Care System (OCS) for normothermic machine perfusion show promising results yet are limited in sample size. This article presents a meta-analysis of heart donation either after brain death (OCS-DBD) or circulatory death (OCS-DCD) on using OCS versus static cold storage used for HTx. Methods. A systematic literature search was performed for articles discussing the use of normothermic ex situ heart perfusion in adult patients. Thirty-day survival outcomes were pooled, and odds ratios were calculated using random-effects models. Long-term survival was visualized with Kaplan-Meier curves, hazard ratios were calculated and pooled using fixed-effects models, and secondary outcomes were analyzed. Results. A total of 12 studies were included, with 741 patients undergoing HTx, of which 260 with the OCS (173 DBD and 87 DCD). No differences were found between the 3 groups for early and late survival outcomes or for secondary outcomes. Conclusions. OCS outcomes, for both DBD and DCD hearts, appeared similar as for static cold storage. Therefore, OCS is a safe and effective technique to enlarge the cardiac donor pool in both DBD and DCD, with additional benefits for long-distance transport and surgically complex procedures

Biomimetic cultivation of atrial tissue slices as novel platform for in-vitro atrial arrhythmia studies

Living myocardial slices (LMS) are beating sections of intact human myocardium that maintain 3D microarchitecture and multicellularity, thereby overcoming most limitations of conventional myocardial cell cultures. We introduce a novel method to produce LMS from human atria and apply pacing modalities to bridge the gap between in-vitro and in-vivo atrial arrhythmia studies. Human atrial biopsies from 15 patients undergoing cardiac surgery were dissected to tissue blocks of ~ 1 cm2 and cut to 300 µm thin LMS with a precision-cutting vibratome. LMS were placed in a biomimetic cultivation chamber, filled with standard cell culture medium, under diastolic preload (1 mN) and continuous electrical stimulation (1000 ms cycle length (CL)), resulting in 68 beating LMS. Atrial LMS refractory period was determined at 192 ± 26 ms. Fixed rate pacing with a CL of 333 ms was applied as atrial tachyarrhythmia (AT) model. This novel state-of-the-art platform for AT research can be used to investigate arrhythmia mechanisms and test novel therapies