Role of advanced echocardiography in the follow-up of pediatric cardiac transplant patients

openPresupposti dello studio. Il trapianto cardiaco in età pediatrica è la strategia risolutiva per l’insufficienza cardiaca end-stage. Fra le complicanze del post-trapianto, quelle che maggiormente impattano sulla prognosi sono il rigetto acuto e lo sviluppo della cardiac allograft vasculopathy (CAV). Pertanto, i pazienti cardiotrapiantati vengono sottoposti ad un follow-up a vita in cui è centrale il ruolo dell’ecocardiografia. Tuttavia, l'eco convenzionale si è dimostrata inadeguata nell’intercettare precocemente eventi avversi. Per cui è crescente l’interesse verso le metodiche di eco avanzata, sebbene attualmente non abbiano un ruolo stabilito nel follow-up. Ciononostante, nell’ottica di individuare marker non invasivi predittivi di eventi avversi, è promettente il ruolo di strumenti avanzati come lo Speckle tracking echocardiography (STE) e il Myocardial Work (MW). Scopo dello studio. Gli obiettivi dello studio sono stati: a) valutare le caratteristiche demografiche e cliniche dei pazienti sottoposti a trapianto cardiaco e attivamente seguiti dalla Cardiologia Pediatrica dell'Azienda Ospedaliera di Padova da gennaio 2008 a luglio 2024; b) definire parametri eco, convenzionali o avanzati, utili nel follow-up dei pazienti cardiotrapiantati e predittivi di outcomes. Materiali e metodi. Sono stati studiati, retrospettivamente, 25 pazienti cardiotrapiantati da gennaio 2008 a luglio 2024 ed attivamente seguiti dal nostro servizio. Per ogni paziente sono stati analizzati esami ecocardiografici seriati eseguiti nel corso del follow-up, in modo da ricostruirne l’andamento nel tempo. Inoltre, sono stati analizzati anche gli esami ecocardiografici eseguiti in concomitanza con la biopsia ed un mese prima e dopo dalla stessa. Questo ha permesso di definire la relazione fra la biopsia ed il quadro ecocardiografico. Per ogni valutazione sono stati ricavati i parametri eco convenzionali e avanzati, fra cui il peak strain dispersion (PSD), lo strain longitudinale globale del ventricolo sinistro (GLS), lo strain della parete libera e globale del ventricolo destro (RV-FWS, GS), il myocardial work (MW) e gli indici derivati. Risultati. I principali risultati individuati dal nostro studio sono: a) il PSD è significativamente aumentato al momento dell’episodio di rigetto nei pazienti presentanti tale evento (p=0,036); b) un valore di GLS ad un mese dal trapianto significativamente diminuito è predittivo dello sviluppo di outcomes compositi (p=0,013); c) il GCW e RV FWS peggiorano significativamente al momento dell’episodio di rigetto rispetto all’assenza dello stesso nel singolo paziente (p=0,045 e p=0,032, rispettivamente). Conclusioni. Il nostro studio è il primo che esplora il ruolo di parametri ecocardiografici avanzati, quali il PSD e il MW, come predittori di rigetto acuto nei pazienti pediatrici sottoposti a trapianto cardiaco. Dal nostro studio emerge l'inadeguatezza dell'ecocardiografia convenzionale nel monitoraggio di questi pazienti. Al contrario, le metodiche avanzate come il 2D-STE e il MW mostrano un potenziale maggiore nel predire eventi avversi. Inoltre, si evince che in questi pazienti il confronto con dei cut-off di riferimento, o tra i diversi pazienti, è del tutto futile. L’unica valutazione predittiva è quella dell’andamento nel tempo dei parametri ecocardiografici avanzati nel singolo paziente. Tali metodiche, per essere incluse routinariamente, necessitano di ulteriore approfondimento.Background. Pediatric heart transplantation represents the only decisive strategy for end-stage heart failure. Among the main complications occurring in the post-transplant period, those with the greatest impact on prognosis are acute rejection and the development of cardiac allograft vasculopathy (CAV). Therefore, heart transplant patients undergo lifelong follow-up in which the role of echocardiography is central. However, conventional echo parameters have proven inadequate in early detection of adverse events. Therefore, there is growing interest in advanced echo methods, although they currently have no standardized role in the follow-up of heart transplant patients. Nevertheless, with a view to identifying non-invasive markers predictive of adverse events, the role of advanced tools such as Speckle tracking echocardiography (STE) and Myocardial Work (MW) is promising. Purpose. The aims of the study were: a) to evaluate the demographic and clinical characteristics of pediatric patients who underwent heart transplantation and were referred to the Pediatric Cardiology Department from January 2008 to July 2024; b) to define conventional or advanced echocardiographic parameters that are useful in the follow-up of heart transplant patients and that can predict overall outcomes. Materials and methods. Twenty-five heart transplant patients, actively followed by the Pediatric Cardiology service at the Padua Hospital, were retrospectively studied from January 2008 to July 2024. Serial echocardiographic exams performed during follow-up were analyzed for each patient to reconstruct the time course of echocardiographic parameters for individual patients. Additionally, echocardiographic exams performed in conjunction with biopsy, as well as one month before and after, were analyzed. This allowed the definition of the relationship between biopsy and the echocardiographic findings. For each evaluation, conventional and advanced echocardiographic parameters were obtained, including peak strain dispersion (PSD), global longitudinal strain of the left ventricle (GLS), strain of the free wall and global strain of the right ventricle (RV-FWS, GS), myocardial work (MW), and derived indices. Results. The main findings identified by our study are: a) the comparison of the presence-absence of rejection groups at reference biopsy showed that at the time of the rejection episode, for those patients who experienced this adverse event, there was a significant increase in PSD (p=0.036); b) patients with a significantly decreased GLS value at one month after transplantation are at higher risk of developing adverse events, making this parameter predictive of composite outcomes (p=0.013); c) GCW and RV FWS are the only advanced echocardiographic indices that significantly worsen at the time of a rejection episode compared to its absence in the same patient (p=0.045 and p=0.032, respectively). Conclusions. Our study is the first to explore the role of advanced echocardiographic parameters, such as PSD and MW, as predictors of acute rejection in pediatric heart transplant patients. Our findings highlight the inadequacy of conventional echocardiographic parameters in monitoring heart transplant patients. In contrast, advanced echocardiographic techniques like 2D-STE and MW show greater potential in predicting adverse events. Furthermore, analysis of the data shows that comparison with reference cut-off values, or between different patients, is completely futile in these patients.The only predictive evaluation is the trend over time of the advanced echocardiographic parameters in the individual patient. However, these methods require further investigation before they can be routinely incorporated into clinical practice

Writing self and race in the early twentieth century: the autobiographical esays of Zitkala-Sa

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Characterization of the reactivity of prothrombin-dependent anti-phospholipid antibodies with apoptotic cells

Anti-phospholipid antibodies (aPL) occur in patients with the anti-phospholipid syndrome, and are directed against various combinations of phospholipids and phospholipid-binding proteins (e.g., beta2-glycoprotein I and prothrombin). Lupus anticoagulants (LA), a subset of aPL, exhibit anticoagulant properties in vitro, but are strikingly procoagulant in vivo. We have previously demonstrated that some aPL bind specifically to apoptotic, but not viable, thymocytes in the presence of beta2-glycoprotein 1. Here, we demonstrate that prothrombin binds selectively to the surface of apoptotic Jurkat cells, and supports the binding of LA-positive murine monoclonal antibodies (mAb) and patient-derived IgG to apoptotic cells. Despite similar LA activity and reactivity with apoptotic cells, the mAb differed in affinity and specificity. One mAb was highly reactive with prothrombin alone, while the other required anionic phospholipid for elevated binding. These results demonstrate that aPL recognize multiple epitopes on apoptotic cells, suggesting that apoptotic antigens contribute to the induction and/or perpetuation of aPL

A novel red blood cell substitute based on crosslinked hemoglobin, superoxide dismutase, and catalase /

Modified hemoglobin red blood cell substitutes have a number of potential areas of application. In some of these applications, it will be important to lessen the pro-oxidant effects of hemoglobin and potential free radical-mediated toxicity. This research introduces a novel modified hemoglobin that is based on intermolecularly crosslinking hemoglobin, superoxide dismutase and catalase (PolyHb-SOD-CAT) with the bifunctional agent, glutaraldehyde. Superoxide dismutase and catalase catalyze the breakdown of superoxide radical and hydrogen peroxide respectively. Studies of structural and functional parameters reveal that PolyHb-SOD-CAT retains superoxide dismutase and catalase enzymatic activity, and consists of a mixture of molecular species ranging in molecular size and protein composition. Circulation time studies of PolyHb-SOD-CAT in rats show that hemoglobin, superoxide dismutase and catalase possess longer circulatory half-lives as compared to the free forms of these proteins. Studies also show that PolyHb-SOD-CAT prevents the formation of methemoglobin, ferrylhemoglobin, hydroxyl radical, free iron, and lipid peroxidation. Ischemia-reperfusion studies using isolated perfused hindlimbs and intestine of rat show that PolyHb-SOD-CAT reduced the formation of hydroxyl radical compared to PolyHb. Altogether, these results suggest that PolyHb-SOD-CAT is a potentially safer modified hemoglobin oxygen carrier by virtue of its ability to detoxify reactive oxygen species, and reduced propensity to promote and participate in oxidative processes

FemTech: A Feminist Technoscience Analysis

This research paper grapples with the oppressive consequences and liberatory possibilities of innovations in menstruation technologies enabled by the Fem- Tech industry. First, it discusses a feminist technoscience framework, tracing some progressions of feminist thought on technology. Then, it reviews popular discourse about FemTech and problematizes some of its implicit assumptions. Using FemTech as a starting point, the paper looks backward in time to some recent histories of menstrual technologies. Finally, it draws on Ursula Franklin’s 1985 discussion about the dichotomy of values that underlie that technological order and those that underlie the women’s world, wondering whether FemTech can serve as a bridge between them. In all, this paper explores how the “femi- nist” label is implicitly and explicitly tied up with FemTech and imagines what truly feminist menstrual technologies could accomplish