Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children

despite the multiple benefits of vaccination, cardiac adverse events following COVID-19 immunization (c-AEFI) have been reported. these events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event

Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel Registry

The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries

An integrated approach to the study of mantle cell lymphoma

La comprensione dei meccanismi molecolari delle malattie sta alla base della medicina moderna. Questo campo di ricerca \ue8 divenuto sempre pi\uf9 interdisciplinare negli anni, sfruttando tecniche sviluppate inizialmente in chimica, biologia sperimentale, immunologia, matematica, informatica etc.. e proprio recentemente, con l'avvento di tecnologie high-throughput, questo tipo di approccio \ue8 diventato pi\uf9 una necessit\ue0 che un lusso. In questo progetto abbiamo utilizzato un approccio integrato per lo studio del linfoma a cellule del mantello (MCL). Nel tentativo di ottenere un quadro pi\uf9 completo, e possibilmente pi\uf9 realistico, della patogenesi di questo linfoma abbiamo cercato di integrare le informazioni ottenute da analisi di tipo proteomico, trascrittomico e genomico per mezzo di diverse tecnologie high-throughput. Nella prima parte del progetto abbiamo sfruttato una tecnica di tipo proteomico, chiamata Phosphoscan, per determinare il proteoma tirosina attivato di un pannello di linee cellulari di MCL. Dato che la fosforilazione su residui tirosinici regola la funzione di molte proteine, questo tipo di approccio ci ha permesso di identificare le vie del segnale pi\uf9 attive nei campioni analizzati. L\u2019analisi Phosphoscan ha rivelato che le cellule del MCL hanno un\u2019attivazione molto forte del recettore delle cellule B (BCR) e inibendo Syk con piceatannolo (una molecola chiave della via di trasduzione del segnale del BCR) si provoca la morte di queste ultime. L'attivazione di questo percorso \ue8 stata quindi verificata anche nei tessuti di tumore MCL, suggerendo che potrebbe essere un obiettivo terapeutico importante. Altre chinasi, oltre a Syk, sono state trovate attivate (fosforilate) e il loro ruolo \ue8 pertanto oggetto di indagine tramite l\u2019utilizzo di inibitori chinasici. Ad ogni modo il meccanismo che guida l\u2019attivazione del BCR \ue8 rimasto irrisolto. La presenza di mutazioni attivanti \ue8 un meccanismo di base della patogenesi del cancro, pertanto abbiamo ipotizzato che la presenza di un\u2019alterazione genetica in una o pi\uf9 delle proteine trovate attive potesse esser responsabile dell\u2019attivazione della via del BCR. Per verificare tale ipotesi abbiamo verificato la presenza di mutazioni nelle sequenze codificanti corrispondenti alle proteine fosforilate pi\uf9 abbondanti, tramite sequenziamento classico di Sanger. Abbiamo cos\uec identificato quattro mutazioni missenso nei geni PRPF4B, BTK, PRKCD e CD79B ma per determinare il loro ruolo sono necessari ulteriori studi funzionali e un estesa validazione in vitro. \uc9 stato recentemente dimostrato che il concetto di stereotipia del BCR \ue8 strettamente correlato alla sua attivazione e alla patogenesi di diversi tipi di linfoma e leucemia, come la leucemia linfatica cronica (B-CLL). Per questo motivo abbiamo analizzato i recettori per l\u2019antigene B di diverse linee cellulari di MCL, alla ricerca di un meccanismo addizionale che potesse stimolare la cascata del segnale. Abbiamo sequenziato i geni sia delle catene pesanti che di quelle leggere del BCR e abbiamo verificato la presenza di motivi stereotipati in queste ultime. Questi risultati mettono in luce il possibile ruolo delle catene leggere nella segnalazione tonica del BCR e forniscono le basi per l\u2019utilizzo di queste linee cellulari come modello per indagare il ruolo di specifici BCR nella patogenesi del MCL. Nella seconda parte del lavoro abbiamo applicato una tecnologia NGS, e precisamente il sequenziamento del RNA, a sette casi di MCL e tre linfonodi reattivi. Questo approccio trascrittomico su larga scala ha il vantaggio di fornire, oltre a un profilo mutazionale completo di tutta la porzione trascritta del campione in analisi, numerose informazioni (profilo di espressione genica, utilizzo di varianti di splicing, trascritti chimerici etc..) che potrebbero esser utili per meglio capire la patogenesi molecolare del MCL. Un\u2019analisi preliminare e guidata dei dati di RNA-seq ci ha permesso di individuare undici mutazioni potenzialmente rilevanti, fra quelle gi\ue0 annotate nel database COSMIC. Solo quattro di queste, presenti nei geni NOTCH2, ATM, GOT2 e CHPF2, sono state validate. Abbiamo inoltre dimostrato la presenza di trascritti di fusione nel MCL, sebbene sterili e rilevabili in un numero molto limitato di casi (si tratta quindi di trascritti prevalentemente \u201cprivati\u201d). Le informazioni ottenute da quest'analisi trascrittomica sono estremamente complesse e quindi necessitano di ulteriori analisi in termini bioinformatici e biologici, che al momento sono ancora in corso. Complessivamente queste analisi hanno portato nuova conoscenza sul meccanismo alla base del processo patogenetico nel MCL, evidenziando il ruolo della via del segnale del BCR.Understanding the mechanisms of disease is the base of modern medicine. Cancer research has become over the years more and more interdisciplinary, using techniques developed initially in other science disciplines, such as chemistry, experimental biology, immunology, mathematics, informatics and many others. In recent years, with the advent of high-throughput techniques, this multi-faceted approach has become a necessity more than a luxury. In this project we exploited an integrated approach to the study of mantle cell lymphoma (MCL). To gain a more complete, and possibly more real, picture of MCL pathogenesis we tried to integrate information coming from proteomic, transcriptomic and genomic studies acquired by means of several modern high-throughput techniques. In the first part of this project we took advantage of a shotgun proteomic technique, called Phoshoscan, to identify the tyrosine-phosphorylation profile of MCL cells. Since tyrosine phosphorylation regulates the activity of many proteins, this approach allowed us to identify the most active pathways in the analyzed samples. The Phosphoscan analysis has shown that MCL bears an aberrant activation of the B-cell receptor (BCR) signaling pathway, and that at least in vitro the inhibition of Syk (a key molecule of BCR signaling) is lethal for MCL cells. Other kinases were also found to be active (phosphorylated) and these are matter of current investigation by means of pharmacological inhibition. However, the mechanism driving BCR activation remained elusive. Since the presence of activating mutations is one basic mechanism of cancer pathogenesis, we hypothesized that a genetic lesion in one or more of the active proteins might be responsible for the abnormal activation of the BCR pathway. To test this hypothesis we looked for the presence of mutations in the coding sequences corresponding to the most abundant Tyr-phosphorilated proteins, taking advantage of the classical Sanger sequencing. We identified four missense mutations in PRPF4B, BTK, PRKCD and CD79B genes but further functional studies and an extensive validation are necessary to assess these mutations role. Since BCR stereotypy and activation have been linked to the pathogenesis of different lymphomas and leukemias, like B-CLL, we also investigated whether MCL cell lines bore stereotyped BCR, as an additional mechanism stimulating the signaling cascade. We determined the precise sequence of rearranged heavy and light chain genes in several MCL cell lines and we found no evidence of heavy chain stereotypy, but recurrent presence of stereotyped light chain. These findings highlight the possible role of light chains in tonic BCR signaling and provide the basis to use MCL cell lines as a model to investigate the role of specific BCRs in the pathogenesis of MCL. In the second part of the work we applied a next-generation sequencing (NGS) technique, RNA-sequencing, to seven cases of MCL and three non-neoplastic lymph node samples. This whole-transcriptome approach has the advantage to provide, beyond a complete mutational profile of the expressed genes, several new data (quantitative gene expression profiling, usage of splice variants, chimeric transcripts etc) which can be useful to better understand the molecular pathogenesis of MCL. A preliminary supervised analysis of RNA-seq data identified eleven putative relevant single-nucleotide variants (SNVs), already annotated in the COSMIC database. Only four of them, affecting NOTCH2, ATM, GOT2, and CHPF2 genes, were validated. Moreover we showed that although fusion transcripts are usually present in MCL, they are detectable in a very limited number of cases (i.e. they are mostly private) and do not produce any detectable protein. However the information obtained from this analysis is extremely wide and complex and deserves a deeper investigation by means of bioinformatic analysis and biological validation that is still ongoing. Overall, these analyses brought us new insights about the mechanism driving the pathogenetic process in MCL, highlighting the role of BCR signaling pathway

Bypass versus angioplasty: Evidence, practice and patient preferences in the light of the new European guidelines on myocardial revascularization,Bypass versus angioplastica: Evidenze, prassi e preferenze del paziente alla luce delle nuove linee guida Europee sulla rivascolarizzazione miocardica

Bypass versus angioplasty: Evidence, practice and patient preferences in the light of the new European guidelines on myocardial revascularization,Bypass versus angioplastica: Evidenze, prassi e preferenze del paziente alla luce delle nuove linee guida Europee sulla rivascolarizzazione miocardic

The role of stent design and polymers in safety outcomes - A review

The role of stent design and polymers in safety outcomes - A revie

Mantle cell lymphoma cell lines show no evident immunoglobulin heavy chain stereotypy but frequent light chain stereotypy

Mantle cell lymphoma shows a peculiar immunogenetic profile, but the functional consequences of this fact are unknown. We have determined the precise sequences of rearranged heavy and light chain genes in several mantle cell lymphoma cell lines and investigated the presence of heavy and light chain stereotypy. These cell lines use IGHV and IGLV genes that are known to be preferentially rearranged in mantle cell lymphoma, but we found no evidence of heavy chain stereotypy. On the contrary, one cell line (Mino) showed a nearly identical light chain complementarity determining region 3 when compared to the only published light chain cluster. Two cell lines couples (Jeko-1/UPN-2 and JVM-2/JVM-13) showed a highly similar light chain, which satisfied the criteria for stereotypy. Our data show that mantle cell lymphoma cell lines resemble the IGHV and IGLV usage of mantle cell lymphoma, and foster the hypothesis that light chain stereotypy might be under-recognized