imaging biomarkers in upper gastrointestinal cancers

In parallel with the increasingly widespread availability of high performance imaging platforms and recent progresses in pathobiological characterisation and treatment of gastrointestinal malignancies, imaging biomarkers have become a major research topic due to their potential to provide additional quantitative information to conventional imaging modalities that can improve accuracy at staging and follow-up, predict outcome, and guide treatment planning in an individualised manner. The aim of this review is to briefly examine the status of current knowledge about imaging biomarkers in the field of upper gastrointestinal cancers, highlighting their potential applications and future perspectives in patient management from diagnosis onwards

Radiomics and Magnetic Resonance Imaging of Rectal Cancer: From Engineering to Clinical Practice

While cross-sectional imaging has seen continuous progress and plays an undiscussedpivotal role in the diagnostic management and treatment planning of patients with rectal cancer, alargely unmet need remains for improved staging accuracy, assessment of treatment response andprediction of individual patient outcome. Moreover, the increasing availability of target therapies hascalled for developing reliable diagnostic tools for identifying potential responders and optimizingoverall treatment strategy on a personalized basis. Radiomics has emerged as a promising, still fullyevolving research topic, which could harness the power of modern computer technology to generatequantitative information from imaging datasets based on advanced data-driven biomathematicalmodels, potentially providing an added value to conventional imaging for improved patient manage-ment. The present study aimed to illustrate the contribution that current radiomics methods appliedto magnetic resonance imaging can offer to managing patients with rectal cancer

Long-term Outcome of Pulmonary Vein Isolation Versus Amiodarone Therapy in Patients with Coexistent Persistent AF and Congestive Heart Failure

Although pharmacological rhythm control of AF in patients with heart failure with reduced ejection fraction (HFrEF) does not seem to provide any benefit over rate control, catheter ablation of AF has been shown to improve clinical outcomes. These results can be explained with higher success rates of catheter ablation in restoring and maintaining sinus rhythm compared with antiarrhythmic drugs. In addition, pharmacotherapy is not void of side-effects, which are thought to offset its potential antiarrhythmic benefits. Therefore, efforts should be made towards optimisation of ablation techniques for AF in patients with HFrEF

Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BACKGROUND: Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. METHODS: Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. RESULTS: During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. CONCLUSIONS: DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation

Dual-Antiplatelet Therapy Cessation and Cardiovascular Risk in Relation to Age: Analysis From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the association between dual-antiplatelet therapy (DAPT) cessation and cardiovascular risk after percutaneous coronary intervention in relation to age. BACKGROUND: Examination of outcomes by age after percutaneous coronary intervention is relevant given the aging population. METHODS: Two-year clinical outcomes, incidence, and effect of DAPT cessation on outcomes were compared by ages ≤55, 56 to 74, and ≥75 years from the PARIS (Patterns of Non-Adherence to Antiplatelet Regimens in Stented Patients) registry. DAPT cessation included physician-recommended discontinuation, interruption for surgery, and disruption (from noncompliance or bleeding). Clinical endpoints were major adverse cardiac events (MACE) (a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, or clinically indicated target lesion revascularization), a secondary restrictive definition of MACE (MACE2) excluding target lesion revascularization, and bleeding. RESULTS: A total of 1,192 patients (24%) were ≤55 years, 2,869 (57%) were 56 to 74 years, and 957 (19%) were ≥75 years of age. Patients ≥75 years of age had higher DAPT cessation rates and increased risk for MACE2, death, cardiac death, and bleeding compared with younger patients. Discontinuation and interruption were not associated with increased cardiovascular risk across age groups, whereas disruption was associated with increased risk for MACE and MACE2 in younger patients but not in patients ≥75 years of age (p for trend <0.05). CONCLUSIONS: Nonadherence and outcomes vary by age, with patients ≥75 years having the highest DAPT cessation rates. We observed no association between outcomes and DAPT cessation in patients ≥75 years, whereas discontinuation was associated with lower MACE rates and disruption with increased MACE rates in patients <75 years

Diagnosis of transitory myocardial ischemia: a second look to old methodologies

Several methodologies have been developed for the detection of myocardial ischemia. However, only electrocardiography and echocardiography, both at rest and during stress, are non-invasive, inexpensive and readily available in almost every center. While ECG remains a pillar in the diagnosis of ischemia, it has been hypothesized that the filters routinely applied to the raw ECG signal to reduce noise, might also cut out clinically relevant signal and result in a lower sensitivity for myocardial ischemia. In fact, most filers remove low frequencies that contain information on the ventricular repolarizations (ST segment and T wave). Here we sought to investigate whether analysis of the raw unfiltered ECG signal might improve our ability to diagnose transient myocardial ischemia. In order to test this, we recorded unfiltered ECGs during percutaneous coronary angioplasty in patients with single coronary artery disease undergoing clinically indicated revascularization. The exact time and duration of intracoronary balloon inflation were recorded. Next, we analyzed the unfiltered raw ECG signal during 30-second long transient coronary occlusions (TCO). The raw ECG signal appears as a fundamental frequency follow by arithmetic harmonics. A significant increase in the signal intensity compared to baseline was found in the fundamental frequency or in one of the first 3 harmonics during every TCO. The increase signal intensity corresponded also to morphological ECG modification that most times met the criteria for the diagnosis of transient myocardial ischemia. We observed a significant correlation between harmonic signal intensity and point J voltage at 60 ms (J60) both at baseline and during TCO. Once we identified a marker of myocardial ischemia in the harmonic signal during TCO, we tried to apply this knowledge to the detection of inducible myocardial ischemia during a stress test. We recorded raw unfiltered ECG traces in patients undergoing stress echocardiography for clinical reasons. Similar to what observed during coronary angiography, ischemic episodes during stress echocardiography presented with a significant increase in signal intensity compared to baseline. The signal intensity significantly correlated with the J60. This is the proof of principle that harmonic ECG signal can be used to identify myocardial ischemia. Further tests will be necessary to evaluate the sensitivity of this type of analysis compared to morphological ECG

La catena pesante della ferritina come reporter gene per la localizzazione delle cellule staminali cardiache

Premessa: la comprensione del comportamento delle cellule staminali dopo trapianto richiede lo sviluppo di nuove tecniche di marcatura e di rilevazione del segnale per il monitoraggio longitudinale della localizzazione e proliferazione cellulare. Scopo: il presente studio si propone di mettere a punto un metodo per il monitoraggio, in vivo, di cellule staminali cardiache residenti impiantate nel muscolo cardiaco e valutare gli effetti di queste cellule nel miocardio infartuato. Metodi: le cellule staminali cardiache residenti sono state ottenute attraverso digestione enzimatica di frammenti tissutali prelevati con biopsie dal miocardio sano di maiale. Una volta isolate le cellule desiderate, le cosiddette cellule formanti cardiosfere (CFCs), esse sono state trasdotte con il gene della catena pesante della ferritina (FTH), veicolato da un vettore virale derivato dal virus dell’immunodeficienza felina (FIV). Le cellule trasdotte così ottenute sono state messe in coltura per permettere la formazione di cardiosfere (Csp) e poi adoperate per gli esperimenti in vivo. Gli animali sono stati suddivisi in quattro gruppi. Gruppo I: animali infartuati che hanno ricevuto una iniezione intramiocardica di soluzione contenente Csp trasdotte (n=7); gruppo II: animali infartuati trattati con Csp non trasdotte (n=4); gruppo III: ratti infartuati trattati con iniezione intramiocardica di PBS (n=7); gruppo IV: ratti sani sottoposti ad iniezione di Csp trasdotte (n=5). L’infarto è stato provocato attraverso legatura della discendente anteriore. L’iniezione di 0,2 ml di campione è avvenuta a 45 minuti dalla chiusura del vaso nella zona adiacente all’infarto. Gli animali sono stati sottoposti a due esami di risonanza magnetica rispettivamente a 1 e 4 settimane dell’iniezione con un apparecchio 1,5 Tesla. La valutazione dell’accumulo di ferro intramiocardico è stata effettuata con sequenze gradient-echo T2* utilizzando multipli tempi di echo (2, 4.4, 6.4, 8.6, 10.8, 13, 15.2, 17.4 msec). Sono state acquisite anche immagini morfologiche e funzionali ed è stata misurata la dimensione dell’infarto grazie al delayed enhancement con mezzo di contrasto. Risultati: la trasduzione della catena pesante della ferritina ha permesso l’accumulo del ferro circolante all’interno delle cellule trapiantate e, quindi, la formazione di un segnale visibile alla RM senza la necessità di somministrare un mezzo di contrasto. Il segnale prodotto dall’accumulo di ferro è ben visibile anche con un apparecchio 1,5 T, ad una settimana dall’iniezione delle cellule ed è quantificabile misurando il valore T2*. Comparato a quello delle altre zone del miocardio, il valore T2* della zona dell’iniezione dei casi trattati con cellule trasdotte risulta nettamente inferiore. Dal punto di vista funzionale, paragonando i dati ottenuti dai ratti infartuati trattati con Csp con quelli degli animali infartuati trattati con solo fisiologica è possibile osservare un miglioramento della frazione di eiezione (FE), e dell’ ispessimento telesistolico nella zona peri-infartuale, sede dell’iniezione; è riscontrabile, inoltre, una riduzione dell’area infartuata negli animali trattati con Csp. L’analisi istologica con la colorazione di Perls ha confermato la presenza di un accumulo di ferro intracellulare. Grazie all’immunoistochimica è stato possibile riscontrare che le cellule iniettate si sono differenziate prevalentemente in fibroblasti e, in misura minore, in cellule endoteliali e cardiomiociti. Conclusioni: l’utilizzo del gene dalla FTH come reporter gene in cellule staminali cardiache residenti si è rivelato essere un metodo di marcatura efficace e sicuro, in grado di produrre un segnale tale da poter essere facilmente visualizzato con un apparecchio a 1,5 T. La RM permette un monitoraggio in vivo accurato delle cellule iniettate, nonché una valutazione della funzione cardiaca globale e regionale. L’accumulo di ferro non è risultato essere tossico per le cellule né, tanto meno, per l’organismo. Le Csp si sono dimostrate efficaci nel migliorare la funzione cardiaca globale e regionale, e nel ridurre l’area infartuata. La FE e la contrattilità parietale nei casi trattati con cardiosfere trasdotte risultano migliori rispetto ai controlli trattati con PBS in maniera statisticamente significativa. La differenziazione delle Csp ha però condotto alla formazione di un numero relativamente modesto di cardiomiociti, il che lascia supporre, in presenza di un miglioramento della funzione, che le Csp abbiano agito, anche e soprattutto, attraverso la secrezione di fattori paracrini in accordo con altri studi, su diversi tipi di cellule staminali, presenti in letteratura

Sinus node dysfunction in catecholaminergic polymorphic ventricular tachycardia: risk factor and potential therapeutic target?

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder characterized by the occurrence of potentially life-threatening polymorphic ventricular tachyarrhythmias in conditions of physical or emotional stress. The underlying cause is a dysregulation in intracellular Ca handling due to mutations in the sarcoplasmic reticulum Ca release unit. Recent experimental work suggests that sinus bradycardia, which is sometimes observed in CPVT patients, may be another primary defect caused by CPVT mutations. Herein, we review the pathophysiology of CPVT and discuss the role of sinus node dysfunction as a modulator of arrhythmia risk and potential therapeutic targe

Pulmonary sequestration: What the radiologist should know

Pulmonary sequestration consists of a nonfunctioning mass of lung tissue, either sharing the pleural envelope of the normal lung (intralobar) or with its own pleura (extralobar), lacking normal communication with the tracheobronchial tree and receiving its arterial supply by one or more systemic vessels. It is the second most common congenital lung anomaly according to pediatric case series, but its real prevalence is likely to be underestimated, and imaging plays a key role in the diagnosis and treatment management of the condition and its potential complications. We will give a brief overview of the pathophysiology, clinical presentation and imaging findings of intra- and extralobar pulmonary sequestration, with particular reference to multidetector computed tomography as part of a powerful and streamlined diagnostic approach