A rare case of acute Clozapine - related thrombogenic myocarditis

Not availabl

Usefulness of transthoracic echocardiogram in management of cardiac involvement in large B-Cell lymphoma: a case report

Primary lymphoma often involve the heart, especially the right side. Prompt diagnosis is necessary to start the right therapy and decrease symptoms and death risk rate. Transthoracic echocardiogram is the first line exam to perform when symptoms are suspicious of mediastinal mass

Cardiac rehabilitation activities during the COVID-19 pandemic in Italy. Position Paper of the AICPR (Italian Association of Clinical Cardiology, Prevention and Rehabilitation)

The COVID-19 outbreak is having a significant impact on both cardiac rehabilitation (CR) inpatient and outpatient healthcare organization. The variety of clinical and care scenarios we are observing in Italy depends on the region, the organization of local services and the hospital involved. Some hospital wards have been closed to make room to dedicated beds or to quarantine the exposed health personnel. In other cases, CR units have been converted or transformed into COVID-19 units. The present document aims at defining the state of the art of CR during COVID-19 pandemic, through the description of the clinical and management scenarios frequently observed during this period and the exploration of the future frontiers in the management of cardiac rehabilitation programs after the COVID-19 outbreak

Extracellular Acidosis Differentially Regulates Estrogen Receptor β-Dependent EMT Reprogramming in Female and Male Melanoma Cells

Clinical outcomes of melanoma patients pointed out a gender disparity that supports a correlation between sex hormone activity on estrogen receptors (ER) and melanoma development and progression. Here, we found that the epithelial-to-mesenchymal transition (EMT) of melanoma cells induced by extracellular acidosis, which is a crucial hallmark of solid cancers, correlates with the expression of ERβ, the most representative ER on melanoma cells. Extracellular acidosis induces an enhanced expression of ERβ in female cells and EMT markers remain unchanged, while extracellular acidosis did not induce the expression of ERβ in male cells and EMT was strongly promoted. An inverse relationship between ERβ expression and EMT markers in melanoma cells of different sex exposed to extracellular acidosis was revealed by two different technical approaches: florescence-activated cell sorting of high ERβ expressing cell subpopulations and ERβ receptor silencing. Finally, we found that ERβ regulates EMT through NF-κB activation. These results demonstrate that extracellular acidosis drives a differential ERβ regulation in male and female melanoma cells and that this gender disparity might open new perspectives for personalized therapeutic approaches

Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGF<i>β</i>-Induced EMT in Human Non-Small Cell Lung Cancer

Growth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGFβ is one of the most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer

Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFβ-Induced EMT in Human Non-Small Cell Lung Cancer

Growth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGFβ is one of the most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer

[Management of patients with type 2 diabetes during cardiac prevention and rehabilitation. An expert opinion from the Italian Alliance for Cardiovascular Rehabilitation and Prevention (ITACARE-P)]

Patients with diabetes, regardless of their cardiovascular disease and their index event, are more and more often referred to Cardiac Rehabilitation Units. These patients usually show high or very high cardiovascular risk, marked disability and poor quality of life. Furthermore, those with older age, frailty, and female sex have even more rehabilitative needs, thus requiring fine individualized approaches. Consequently, in order to identify their therapeutic goals, the glycemic target should be pursued together with the effective reduction of the global cardiovascular risk. Modern exercise protocols are based on the synergic effect of both aerobic and strength training of moderate and high effort intensities, in order to achieve improvements of cardiorespiratory fitness and glycemic values as well. Exercise training and nutritional intervention are strictly related during the rehabilitation program, thus promoting better lifestyle in the long term too. New antidiabetic drugs (such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists) should be included into a specific "patient journey" along with other core components of the rehabilitation program. Therefore, the active role of all allied professionals (namely nurses, physiotherapists, dietitians and psychologists) is essential to the success of the cardiometabolic team. Diabetes should be routinely included in the outcome evaluation of cardiac rehabilitation programs and in every follow-up plan through a successful crosstalk among cardiologists, diabetologists and patients

Cell-targeted c(AmpRGD)-sunitinib molecular conjugates impair tumor growth of melanoma

Drug resistance and off-organ toxicity remain unsolved issues in chemotherapy of advanced-stage melanoma patients. Thus, the creation of new molecular conjugates able to combine a selective accumulation, high ability of internalization and signaling pathway inhibition, are highly requested. Recently, we reported a new class of molecular conjugates, compounds 1–3, where the anti-αVβ3 integrin peptidomimetic c(AmpRGD), which is a selective ligand for αVβ3 integrin, was covalently bound to the tyrosine kinase inhibitor sunitinib. Here, we report that these c(AmpRGD)-sunitinib conjugates and, in particular, compound 3, are selectively internalized by human melanoma cells through αVβ3 receptor-mediated endocytosis. Compound 3 is more effective than sunitinib in reducing in vitro melanoma cells proliferation, cloning efficiency, migration, and invasion. More interestingly, compound 3 is able to significantly reduce the growth of xenografted melanoma tumor developed in immune-compromised mice, more efficiently than an equimolar dose of sunitinib. Indeed, its targeting ability was demonstrated by the selective localization at the tumor level with respect to healthy tissues. Thus, c(AmpRGD)-sunitinib conjugates such as compound 3 could serve as intriguing multiple-target agents to selectively reach melanoma cells and interfere with the progression of the disease

miR-214-Enriched Extracellular Vesicles Released by Acid-Adapted Melanoma Cells Promote Inflammatory Macrophage-Dependent Tumor Trans-Endothelial Migration

The understanding of the molecular mechanisms leading to melanoma dissemination is urgently needed in view of the identification of new targets and the development of innovative strategies to improve patients&rsquo; outcomes. Within the complexity of tumor intercellular communications leading to metastatic dissemination, extracellular vesicles (EV) released by tumor cells are central players. Indeed, the ability to travel through the circulatory system conveying oncogenic bioactive molecules even at distant sites makes EV capable of modulating recipient cells to facilitate metastatic dissemination. The dynamic remodeling of the tumor microenvironment might influence, along with a number of other events, tumoral EV release. We observed that, in melanoma, extracellular acidosis increases the release of EV enriched in miR-214, an onco-miRNA involved in melanoma metastasis. Then, miR-214-enriched EV were found to induce a state of macrophage activation, leading to an overproduction of proinflammatory cytokines and nitric oxide. Such an inflammatory microenvironment was able to alter the endothelial cell permeability, thereby facilitating the trans-endothelial migration of melanoma cells, a crucial step in the metastatic cascade. The use of synthetic miR-214 inhibitors and miR-214 overexpression allowed us to demonstrate the key role of miR-214 in the EV-dependent induction of macrophage activation. Overall, our in vitro study reveals that the release of tumor miR-214-enriched EV, potentiated by adapting tumor cells to extracellular acidosis, drives a macrophage-dependent trans-endothelial migration of melanoma cells. This finding points to miR-214 as a potential new therapeutic target to prevent melanoma intravasation

Home defibrillation: A feasibility study in myocardial infarction survivors at intermediate risk of sudden death

Background Out-of-hospital cardiac arrest occurs at home in 65-80% of cases and is often witnessed. We designed a study to explore the feasibility of a home defibrillation program (a) evaluating the retention of cardiopulmonary resuscitation and automated external defibrillators (AED) use skills (BLSD) (b) assessing the impact on anxiety, depression, and quality of life and (c) recording the critical issues emerging from program implementation. Methods Thirty-three post-myocardial infarction patients and their 56 relatives received BLSD training and an AED. Assessment of BLSD skills, levels of anxiety, and depression and quality of life were scheduled every 3 months for 1 year or until a common stopping date. Results Overall BLSD score was 26 +/- 3 at baseline vs. 22 +/- 5 at 3 months (P < .0001), 21 +/- 6 at 6 months (P < .0001), 22 +/- 4 at 9 months (P < 0.0001) and 23 +/- 5 at 12 months (P = .001). Conversely, the BLSD component "AED use"-remained stable throughout the study. Quality of life, anxiety, and depression scores remained constant. Compliance to BLSD retraining sessions and AEDs checks decreased over time and was influenced by a concomitant clinical appoinment. Conclusions BLSD performance of families of post-myocardial infarction patients decreases over time, even though the ability to operate AEDs appears to be the least affected component. Compliance with retraining sessions and AED checks declines over time and is improved if they are combined with clinical appointments. The implementation of a home defibrillation program does not affect anxiety, depression, or the quality of life