Efficacy and safety of anti-cytomegalovirus prophylaxis versus pre-emptive approaches with valganciclovir in heart transplant recipients treated with everolimus or mycophenolate

Il CMV è l’agente patogeno più frequente dopo trapianto (Tx) di cuore determinando sia sindromi cliniche organo specifiche sia un danno immunomediato che può determinare rigetto acuto o malattia coronarica cronica (CAV). I farmaci antivirali in profilassi appaiono superiori all’approccio pre-sintomatico nel ridurre gli eventi da CMV, ma l’effetto anti-CMV dell’everolimus (EVE) in aggiunta alla profilassi antivirale non è stato ancora analizzato. SCOPO DELLO STUDIO: analizzare l’interazione tra le strategie di profilassi antivirale e l’uso di EVE o MMF nell’incidenza di eventi CMV correlati (infezione, necessità di trattamento, malattia/sindrome) nel Tx cardiaco. MATERIALI E METODI: sono stati inclusi pazienti sottoposti a Tx cardiaco e trattati con EVE o MMF e trattamento antivirale di profilassi o pre-sintomatico. L’infezione da CMV è stata monitorata con antigenemia pp65 e PCR DNA. La malattia/sindrome da CMV è stato considerato l’endpoint principale. RISULTATI: 193 pazienti (di cui 10% D+/R-) sono stati inclusi nello studio (42 in EVE e 149 in MMF). Nel complesso, l’infezione da CMV (45% vs. 79%), la necessità di trattamento antivirale (20% vs. 53%), e la malattia/sindrome da CMV (2% vs. 15%) sono risultati significativamente più bassi nel gruppo EVE che nel gruppo MMF (tutte le P<0.01). La profilassi è più efficace nel prevenire tutti gli outcomes rispetto alla strategia pre-sintomatica nei pazienti in MMF (P 0.03), ma non nei pazienti in EVE. In particolare, i pazienti in EVE e strategia pre-sintomatica hanno meno infezioni da CMV (48 vs 70%; P=0.05), e meno malattia/sindrome da CMV (0 vs. 8%; P=0.05) rispetto ai pazienti in MMF e profilassi. CONCLUSIONI: EVE riduce significamene gli eventi correlati al CMV rispetto al MMF. Il beneficio della profilassi risulta conservato solo nei pazienti trattati con MMF mentre l’EVE sembra fornire un ulteriore protezione nel ridurre gli eventi da CMV senza necessità di un estensivo trattamento antivirale.Cytomegalovirus (CMV) is the most clinically relevant infectious agent in heart transplant (HT) recipients. Although antiviral agents used in prophylaxis seem superior to a pre-emptive approach to reduce CMV burden and its consequences, the impact of the additional anti-CMV effect of everolimus (EVE) on the benefit of antiviral prophylaxis is currently unexplored. We analyzed the interaction of anti-CMV strategy and the use of EVE or mycophenolate (MMF) on the occurrence of CMV events in de novo HT recipients. METHODS AND MATERIALS: Consecutive HT recipients surviving at least 6 months after surgery, treated with either EVE or MMF, and transplanted between 2005 and 2010 entered the study. Oral valganciclovir or i.v. ganciclovir were used for pre-emptive or prohylaxis strategy. CMV infection was regularly monitored with CMV DNA PCR and pp65 antigenemia in all patients. CMV disease/syndrome was the main outcome event. RESULTS: 191 patients (11% D+/R-) entered the study (44 on EVE and 147 on MMF). Overall, CMV infection (45% vs. 78%), need for CMV treatment (20% vs. 53%), CMV disease/syndrome (2% vs. 15%), and peak CMV burden (4 vs. 27 pp65cells/205) were significantly lower in EVE than in MMF treated recipients (all P<0.01). Prophylaxis resulted more effective in preventing all these outcomes than pre-emptive strategy in MMF patients (all P 0.03), but not in EVE treated patients. Of note, EVE patients followed with pre-emptive approach showed less CMV infection (48 vs 70%; P=0.05), and less CMV syndrome/disease (0 vs. 8%; P=0.05) than MMF patients receiving prophylaxis. CONCLUSIONS: EVE-based immunosuppression showed a clinically relevant impact on all acute CMV outcomes as compared with MMF. The benefit of anti-CMV prophylaxis is retained only in MMF treated patients and EVE seems to provide an overall advantage in reducing acute CMV events without the need of extensive treatment with antiviral drugs

FVG-Europa: ultima chiamata. Un "porto-regione" tra Mediterraneo e Centro Europa

Il libro tratta di come trasformare una opportunit\ue0 geografica in un concreto progetto territoriale. L\u2019opportunit\ue0 consiste nel valorizzare la favorevole posizione geografica del Friuli Venezia Giulia \u2013 tra il Mediterraneo e le regioni pi\uf9 produttive dell\u2019area germanica \u2013 dal punto di vista dei commerci marittimi e terrestri. Cogliere tale opportunit\ue0, certificata in primo luogo dall\u2019Unione Europea (con la recente approvazione, da parte del Parlamento europeo, del Corridoio Adriatico-Baltico) e da grandi organizzazioni internazionali, potrebbe rilanciare profondamente un\u2019economia regionale in forte declino. Il libro indica puntualmente una strada ancora percorribile per raggiungere l\u2019obiettivo fino a ora mancato: mettere a sistema, in pochi anni e senza grandi investimenti, tutte le strutture e infrastrutture regionali gi\ue0 esistenti (ma che oggi sono mal o sotto-utilizzate) in un unico \u2018porto-regione\u2019. Perch\ue9, allora, l\u2019\uabultima chiamata\ubb? Perch\ue9 questa stessa idea ce l\u2019hanno anche altre realt\ue0 \u2013 oggi in Slovenia e domani, forse, in Croazia \u2013 e se il Friuli Venezia Giulia non si muove subito non ci sar\ue0 pi\uf9 spazio per un altro porto-regione nell\u2019Alto Adriatico con tutto ci\uf2 che ne pu\uf2 conseguire in termini di inevitabile ulteriore declino, non solo della nostra economia ma anche di quella dell\u2019Italia adriatica

Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: A pilot, randomized, intravascular ultrasound study

Background: Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold. Methods: This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) &lt;100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of &lt;100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters. Results: Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p &lt; 0.05). Few patients developed an increase in maximal intimal thickness of &gt;0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p &lt; 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02). Conclusions: Despite being as effective as the titrated-dosing approach in achieving LDL &lt;100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries

Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 \ub1 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 \ub1 6 months) and after (20 \ub1 14 months) HT. In the CHF phase, lower peak oxygen consumption (V\u307O 2) (odds ratio 0.69, P=0.017) independently predicted peak V\u307O 2 improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and V\u307E (ventilation)/V\u307CO 2 (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak V\u307O 2 are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI 6528 and/or a V\u307E/V\u307CO 2 slope 6547 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients