Marinobufagenin (MBG) is a member of the bufadienolide family of compounds, which are natural cardiac glycosides found in a variety of animal species, including man, which have different physiological and biochemical functions but have a common action on the inhibition of the adenosine triphosphatase sodium-potassium pump (Na+/K+-ATPase). MBG acts as an endogenous cardiotonic steroid, and in the last decade, its role as a pathogenic factor in various human diseases has emerged. In this paper, we have collated major evidence regarding the biological characteristics and functions of MBG and its implications in human pathology. This review focused on MBG involvement in chronic kidney disease, including end-stage renal disease, cardiovascular diseases, sex and gender medicine, and its actions on the nervous and immune systems. The role of MBG in pathogenesis and the development of a wide range of pathological conditions indicate that this endogenous peptide could be used in the future as a diagnostic biomarker and/or therapeutic target, opening important avenues of scientific research.

Background and Aims The management of complications of arteriovenous fistula (AVF) for hemodialysis, principally stenosis, remains a major challenge for clinicians with a substantial impact on health resources. Stenosis not infrequently preludes to thrombotic events with the loss of AVF functionality. A frequent monitoring with physical examination is at the basis for an appropriate clinical care. It includes a regular inspection, palpation and auscultation of the arm. A normally functioning AVF, when listened by a stethoscope, has a continuous systolic-diastolic low-frequency murmur while with stenosis the frequency of the murmur increases and the duration of diastolic component decreases, disappearing in severe stenosis. These evidences are strictly subjective and dependent from operator skill and experience. New generation digital stethoscopes are able to record sound and subsequently dedicated software allows to extract quantitative variables (amplitude and frequency) that characterize the sound in an absolutely objective and repeatable way. The aim of our study was to analyze with an appropriate software listenable sound from AVFs taken by a commercial digital stethoscope and to investigate the potentiality to develop an objective new monitoring system to detect stenosis. Method Between September 2022 and January 2023, we screened forty-eight patients from two hemodialysis centers in Catanzaro (Italy). Patients were screened from two blinded experienced examiners for recognized criteria for stenosis by doppler ultrasound (DUS). We recorded the sound coming from the AVFs using a 3M™ Littmann® CORE Digital Stethoscope 8570 (Figure 1-A), in standardized sites: on the anastomosis chamber, at a distance of 5 and 10 cm from it, on the site of stenosis and immediately after. The sound waves were transformed into quantitative variables (amplitude and frequency) using a sound analysis software. Results Based on doppler evaluation, 14/48 patients (29%) were classified as stenotic of which three were hemodynamically significant. The sounds detected in the stenosis sites had a significant higher average frequency compared to non-stenotic sites (Figure 1-B). Characteristics of sound waves were significant different for stenotic and non-stenotic patients in term of average power, mean amplitude and mean frequency. Analysis of waves permitted us to determine peculiar shape for stenosis and another for normal AVF (Figure 1-C,D). Conclusions The analysis of sound waves by a digital stethoscope permitted us to distinguish between stenotic and no stenotic AVFs. The standardization of this technique and the introducing of data in a deep learning algorithm could allow an objective and fast method for a frequent monitoring of AVF.

Background and Aims Hemodialysis sessions exert an acute impact on cardiac geometry and mechanics. The recent development of quantitative measurement of intracardiac fluid-dynamics and analysis of vortexes offers a new opportunity to better understand the fine changes in intracardiac hemodynamic associated with hemodialysis sessions. Vortexes rise in cardiac chambers from blood flow and they are defined as circular fluid structures with rotational movement around a central virtual axis, capable of storing kinetic energy during rotation. They must be distinguished from turbulences, in which various vortexes of different sizes coexist chaotically, resulting in a rapid dissipation of kinetic energy. Our aim was to assess the impact of a hemodialytic session on new parameters originated from intracardiac flow dynamics. Method We included 26 consecutive patients on chronic hemodialysis in clinically stable phase. They underwent echocardiography including intracardiac fluid-dynamic analysis by Color Vector Flow Mapping (Hyperdoppler) before and after a single dialysis session(Fig. 1-A). Patients with hemodynamically relevant valvular disease were excluded. A complete fluid-dynamics evaluation included the measurement of multiple parameters such as vortex area (VA); vortex length (VL); vortex depth (VD). Bland Altman Plot has been used to assess intra and inter-observer variability. Changes in fluid dynamics after dialysis sessions were tested using the Wilcoxon matched-pairs test. Results The Mean Vortex Area (VA) (p = 0.034) (Fig. 1-B), Vortex Depth (VD) (p = 0.024) (Fig. 1-C) and Vortex Length (L) (p = 0.037) (Fig. 1-D) were significantly reduced after the dialysis session. A similar trend towards the reduction of Direct Flow (DF) parameter after the session was found, which was significantly larger for patients with larger baseline left ventricular (V) end-diastolic diameter (r = 0.446; p = 0.037) (Fig. 1-E). On the other hand, mean Vortex Intensity (VI) was significantly increased after dialysis (p = 0.046) (Fig. 1-F). Among energy parameters, the intradialytic change in Kinetic Energy Fluctuation (KEF) (r = 0.4; p = 0.058) and Shear Stress Fluctuation (SSF) (r = 0.435; p = 0.038) (Fig. 1-G) were most closely correlated with intradialytic weight change. Fluid dynamic parameters had similar trends of intradialytic change, with stronger correlations among geometric parameters. Delta changes in VA were closely related to changes in VI (p<0.001) or LV (p<0.001). VI was also correlated with VL (p<0.001) and with Kinetic Energy Dissipation (KED) (p = 0.030), which was also correlated with VL (p = 0.044). KEF was correlated with KED (p = 0.001) and SSF ( = 0.022). Finally, changes in SSF were correlated with those in Flow Force Parameter (p = 0.033) and Flow Force Angle (p = 0.034), that were very closely correlated each other (p<0.001). Conclusion This is the first study assessing the impact of haemodialytic sessions on intracardiac flow dynamics. Measurement of hyperdoppler indices on haemodialysis chair was feasible and reliable in the whole population. Our results uncovered quantitative changes of echocardiographic parameters of vortex geometry and energy during haemodialysis.