Imaging characterization of non-hypersecreting adrenal masses. Comparison between MR and radionuclide techniques.

AIM: In patients with non-hypersecreting adrenal masses, tumor characterization is clinically relevant to establish the appropriate treatment planning. The aim of this study was to comparatively characterize such adrenal lesions using MR and radionuclide techniques. METHODS: Thirty patients with non-hypersecreting unilateral adrenal tumors underwent both MR and adrenal scintigraphy. MR was performed using SE T1- (pre- and post-gadolinium DTPA) and T2-weighted images as well as in- and out-phase chemical-shift imaging (CSI). MR qualitative and quantitative (signal intensity ratios) evaluation was performed. Radionuclide studies consisted of iodine-131 nor-cholesterol (n=20), iodine-131 MIBG (n=15) and fluorine-18 FDG PET (n=11) scans. Histology (n=16), biopsy (n=3) or clinical-imaging follow-up (n=11) demomstrated 13 adenomas, 3 cysts, 2 myelolipomas, 4 pheochromocytomas (pheos), 4 carcinomas, 1 sarcoma and 3 metastases. Comparative imaging analysis was focused on adenomas, pheos and malignant tumors. RESULTS: Qualitative MR evaluation showed: signal T2-hyperintensity in 46% of adenomas and in 100% of pheos and malignant tumors, no gadolinium enhancement in 92% of adenomas and definite signal intensity loss on CSI in 100% of such tumor lesions, gadolinium enhancement in 100% of pheos and in 63% of malignancies and no absolute change of signal intensity on CSI in 100% of both pheos and malignancies. Quantitative MR analysis demonstrated: significantly higher signal T2-hyperintensity of pheos compared to adenomas and malignancies as well as significantly higher enhancement after gadolinium in pheos compared to adenomas and malignancies (p<0.03). Radionuclide studies showed significantly increased nor-cholesterol uptake only in adenomas (n=13), significant MIBG accumulation only in pheos (n=4) and FDG activity only in malignant adrenal lesions (n=8). CONCLUSION: MR techniques may provide some presumptive criteria to characterize non-hypersecreting adrenal masses, such as no gadolinium enhancement and definite signal intensity loss on CSI in adenomas or quantitatively measured T2-hyperintensity and gadolinium enhancement in pheos. On the other hand, radionuclide modalities offer more specific findings in this setting since nor-cholesterol and MIBG scans are respectively able to reveal benign tumors such as adenoma and pheochromocytoma, while FDG imaging allows identification of malignant adrenal lesions. Adrenal scintigraphy is recommended in those patients, when MR images are uncertain or inconclusive

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue

False iodine-131 MIBG scintigraphy findings in adrenal tumors: correlation with MR imaging

AbstractIn this study, we report our experience regarding the occurrence of false radionuclide findings in adrenal iodine-131 MIBG scintigraphy. We present a total of five patients in which nuclear images were false negative or positive in three and two cases, respectively, according to the standard radionuclide established criteria. In particular, the three cases of false-negative MIBG images consisted of two patients with necrotic or cystic pheochromocytomas (Cases 1 and 3) and a patient with a small pheochromocytoma (Case 2); the two cases of false-positive MIBG imaging consisted of a patient with an adenoma showing intense tracer uptake and of a large primary necrotic carcinoma with heterogeneous tracer concentration

Cardiac and Vascular Microenvironment: Biological and Clinical Implications in Cardiology

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Can Beta-2-Adrenergic Pathway Be a New Target to Combat SARS-CoV-2 Hyperinflammatory Syndrome?—Lessons Learned From Cancer

SARS-CoV-2 infection is a new threat to global public health in the 21st century (2020), which has now rapidly spread around the globe causing severe pneumonia often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE2). The progression of Covid-19 has been divided into three main stages: stage I—viral response, stage II—pulmonary phase, and stage III—hyperinflammation phase. Once the patients enter stage III, it will likely need ventilation and it becomes difficult to manage. Thus, it will be of paramount importance to find therapies to prevent or slow down the progression of the disease toward stage III. The key event leading to hyperinflammation seems to be the activation of Th-17 immunity response and Cytokine storm. B2-adrenergic receptors (B2ARs) are expressed on airways and on all the immune cells such as macrophages, dendritic cells, B and T lymphocytes. Blocking (B2AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFNγ. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, we speculate that targeting B2AR in the early phase of Covid-19 might be beneficial to prevent hyperinflammation

Management of QT prolongation induced by anti-cancer drugs: Target therapy and old agents. Different algorithms for different drugs

The side effects of anticancer drugs still play a critical role in survival and quality of life. Although the recent progresses of cancer therapies have significantly improved the prognosis of oncologic patients, side effects of antineoplastic treatments are still responsible for the increased mortality of cancer survivors. Cardiovascular toxicity is the most dangerous adverse effect induced by anticancer therapies. A survey conducted by the National Health and Nutrition Examination, showed that 1807 cancer survivors followed up for seven years: 51% died of cancer and 33% of heart disease (Vejpongsa and Yeh, 2014). Moreover, the risk of cardiotoxicity persists even with the targeted therapy, the newer type of cancer treatment, due to the presence of on-target and off-target effects related to this new class of drugs. The potential cardiovascular toxicity of anticancer agents includes: QT prolongation, arrhythmias, myocardial ischemia, stroke, hypertension (HTN), thromboembolism, left ventricular dysfunction and heart failure (HF). Compared to other cardiovascular disorders, the interest in QT prolongation and its complications is fairly recent. However, oncologists have to deal with it and to evaluate the risk-benefit ratio before starting the treatment or during the same. Electrolyte abnormalities, low levels of serum potassium and several drugs may favour the acquired QT prolongation. Treatment of marked QT prolongation includes cardiac monitoring, caution in the use or suspension of cancer drugs and correction of electrolyte abnormalities (hypokalaemia, hypomagnesaemia, hypocalcaemia). Syndrome of QT prolongation can be associated with potentially fatal cardiac arrhythmias and its treatment consists of intravenous administration of magnesium sulphate and the use of electrical cardioversion

A implementação do roteiro turístico Osório rural : um estudo sobre a articulação de atores públicos e privados

Esta pesquisa se propõe a compreender os valores e os interesses que estimularam a conformação da rede, de atores públicos e privados, que constituiu o roteiro turístico Osório Rural. Com intuito de criar condições de viabilidade metodológica e alcançar os resultados propositivos desta pesquisa de caráter qualitativo, foram estabelecidos os seguintes objetivos específicos: caracterizar os atores envolvidos na formação do roteiro de turismo e suas formas de atuação; identificar os valores e os interesses que influenciaram os atores a participarem da formação do roteiro; descrever o perfil das propriedades e as características dos produtos e serviços ofertados no roteiro; e identificar as fontes de recursos e apoio institucional ao roteiro. O referencial teórico que sustenta esta pesquisa é baseado nos conceitos de nova ruralidade, turismo rural, governança em rede no turismo e, por fim, redes de políticas públicas. Esta pesquisa caracteriza-se como estudo de caso. Os meios utilizados para a obtenção dos dados foram: entrevistas semiestruturadas e pesquisa documental. Desta análise emergiram dez categorias iniciais, três intermediárias e duas finais. Como principais resultados observa-se, em termos gerais, que o roteiro Osório Rural tem potencial de crescimento e pode vir a contribuir com a consolidação do turismo rural na região, dispondo de diversos atrativos naturais, fácil localização e articulação de parcerias públicas e privadas, aspectos favoráveis que corroboram com esta intenção. Contudo, para se tornar referência no turismo rural, as atividades precisam estar organizadas de modo sistêmico e integrado, portanto, uma alternativa para estruturar a atividade turística e fortalecer a interação entre os atores, gerando condições favoráveis no uso das vantagens competitivas, seria adotar um modelo de gestão colaborativa, que garanta fundamentalmente o espírito democrático de fazer política, mantendo vínculos de confiança.This research aims to understand the values and interests that stimulated the formation of the network, of public and private actors, which constituted the Osório Rural tourist route. In order to create conditions for methodological viability and achieve the proposed results of this qualitative research, the following specific objectives were established: characterize the actors involved in the formation of the tourism itinerary and their ways of acting; identify the values and interests that influenced the actors to participate in the formation of the script; describe the profile of the properties and the characteristics of the products and services offered in the script; and identify sources of funding and institutional support for the roadmap. The theoretical reference that supports this research is based on the concepts of new rurality, rural tourism, network governance in tourism and, finally, public policy networks. This research is characterized as a case study. The means used to obtain the data were: semi-structured interviews and documental research. From this analysis, ten initial, three intermediate and two final categories emerged. As main results, it is observed, in general terms, that the Osório Rural route has growth potential and may contribute to the consolidation of rural tourism in the region, having several natural attractions, easy location and articulation of public and private partnerships, favorable aspects that corroborate this intention. However, to become a reference in rural tourism, activities need to be organized in a systemic and integrated way, therefore, an alternative to structure the tourist activity and strengthen the interaction between the actors, generating favorable conditions in the use of competitive advantages, would be to adopt a collaborative management model, which fundamentally guarantees the democratic spirit of doing politics, keeping bonds of trust

Correlative imaging of cystic lymphangiomas: ultrasound, CT and MRI comparison

Cystic lymphangioma is a rare benign lesion derived from the detachment of the lymph sacs from venous drainage systems; the treatment of choice is a surgical excision and the final diagnosis is of histological type