Cardiotoxicity in HER2-positive breast cancer patients.

Due to the recent advances in diagnosis and management of patients with HER2-positive breast cancer, especially through novel HER2-targeted agents, cardiotoxicity becomes an emerging problem. Although chemotherapy significantly increases survival, the risk of cardiovascular disease development is high and still underestimated and could imply treatment discontinuation. Frequently, due to lack of rigorous diagnosis strategies, cardiotoxicity assessment is delayed, and, moreover, the efficacy of current therapy options in restoring heart function is questionable. For a comprehensive risk assessment, it is vital to characterize the clinical spectrum of HER2-targeted agents and anthracyclines, as well as their pathogenic pathways involved in cardiotoxicity. Advanced cardiovascular multimodal imaging and circulating biomarkers plays primary roles in early assessing cardiotoxicity and also in guiding specific preventive measures. Even though the knowledge in this field is rapidly expanding, there are still questions that arise regarding the optimal approach in terms of timing and methods. The aim of the current review aims to providean overview of currently available data.

Phenotypes of hypertrophic cardiomyopathy: genetics, clinics, and modular imaging.

Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular disease with genetic transmission, characterized by the hypertrophy of any segment of the left ventricle (LV), not totally explained by improper loading conditions, with LV systolic function preserved, increased, or reduced. The histopathological mechanism involved in HCM refers to the primary injury of the myocardium, as follows: disorganized array of myocytes, extracellular matrix modification, microvascular dysfunction, with subsequent appearance of myocardial fibrosis. Multiple sarcomere proteins mutations are responsible for HCM, but two of them are involved in 70% of the cases of HCM: ß-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). The development of new genetic techniques involving genome editing is promising to discover a gene therapy for patients with HCM. Clinical presentation may differ from asymptomatic to sudden cardiac death (SCD), the last one targeting younger adults. In this case, the diagnosis and evaluation of SCD risk factors is extremely important. The common method of diagnosis is transthoracic echocardiography, but cardiac magnetic resonance (CMR) imaging represents "gold standard" in the evaluation of HCM patients. Treatment includes pharmacological therapy, surgery, alcohol ablation, and not least SCD prevention.

A 63-year-old woman with multiple secondary tumours.

Clinical introductionA 63-year-old woman recently diagnosed with lung metastasis, after routine chest radiography, was admitted to our hospital for unspecified symptoms, such as dyspnoea on minimal exertion and dry cough. Physical examination showed uncommon signs. The electrocardiogram showed sinus rhythm and incomplete left bundle branch block. Thoracic CT scan revealed bilateral lung and pleural metastases and pelvic CT showed a right femoral bone mass. Transthoracic echocardiography revealed a heterogeneous mass, lateral to the right ventricle, with pericardial effusion. Further, cardiac MRI (cMRI) was performed (figure 1A,B). Diagnosis was completed with an ultrasound-guided biopsy and histopathological examination (figure 1C,D).heartjnl;106/3/202/F1F1F1Figure 1(A,B) Cardiac MRI: asterisk is suggestive of fluid and the white arrow indicates fibrous encapsulation by LGE, (C) H&E stain:white arrow indicating a tumoral cell with atypical mitosis and (D) immunohistochemical staining for smooth muscle actin antibody. QUESTION: Which of the following is the most likely diagnosis?Pericardial lymphoma.Pericardial leiomyosarcoma.Pericardial cyst.Secondary malignant cardiac tumour.Pericardial teratoma.

The role of advanced multimodality imaging in chronic mitral regurgitation.

Mitral regurgitation (MR), the second most common valvular heart disease, still constitutes a major diagnostic and thera-peutic challenge, due to its complex nature and to its consequences on cardiac remodelling. Life quality and expectancy are determined by the irreversibility of the left ventricular systolic dysfunction, which, despite current guidelines, remains a major drawback. In order to accurately establish "the point of no return" for left ventricular systolic function, the embedment of clinical, biological and imaging data is a requirement. The purpose of this review is to provide an overview of the current multimodal imaging techniques that are useful in correctly assessing patients with MR. Cardiac magnetic resonance strain imaging techniques and 3D echocardiography, in addition to current echocardiographic criteria may help identify the patients who will benefit from early surgery. The technical development of new transcatheter techniques in mitral valve repair could lead to the extension of current guidelines.

Pentraxin-3 and endothelial dysfunction.

Pentraxin 3 (PTX3) is involved in vascular inflammation and endothelial dysfunction through various mechanisms. Until now, most studies confirmed an important link between PTX3 and endothelial dysfunction and identified several pathogenetic pathways. PTX3 modulates inflammatory cells, thus stimulating vascular inflammation. Within endothelial cells, it decreases nitric oxide (NO) synthesis, inhibits cell proliferation and alters their functions. PTX3 blocks the effect of fibroblast growth factor 2 (FGF2) by making a molecular complex with these molecules inactivating them. However, there are substances like the tumor necrosis factor-inducible gene 6 protein (TSG-6) that block the PTX3-FGF2 interaction. Interacting with P-selectin, it promotes vascular inflammatory response and endothelial dysfunction. PTX3 also increases the matrix metalloproteinases synthesis directly or by blocking NO synthesis. From a clinical point of view, PTX3 positively correlates with arterial hypertension, flow mediated dilation and, with intima media thickness. Therefore, the involvement of PTX3 in the pathogenesis and evaluation of endothelial dysfunction is clear, and it may become a biomarker in this direction, but further studies are needed to determine its reliability in this direction. Last but not least, PTX3 could become an effective therapeutic target for preventing this dysfunction, but further research needs to be conducted.

Catheter ablation of a right posterior accessory pathway in a patient with left ventricular noncompaction: A case report.

RTIONALE: Left ventricular noncompaction (LVNC) is a genetic cardiomyopathy characterized by the presence of a thin compacted layer of myocardium and a spongy subendocardial layer with trabeculations and recesses. LVNC associated Wolf-Parkinson-White syndrome is very rare. PATIENT CONCERNS: A 32-year-old male presented with short episodes of palpitations and a syncope 6 months before his hospitalization. DIAGNOSIS: His ECG revealed the presence of a right posterior accessory pathway. Echocardiography identified trabeculations of the septal, apical, and lateral wall of the left ventricle, consistent with left ventricular noncompaction. Cardiac MRI confirmed the diagnosis, as the ratio between the noncompacted and compacted myocardial layer was 2.3. INTERVENTIONS: The electrophysiological study revealed a malignant right posterior accessory pathway. Catheter ablation was successfully performed at the level of posterior tricuspid annulus. Programmed ventricular stimulation could not induce any arrhythmia at the end of the procedure. OUTCOMES: During 15 months of follow-up, the patient presented no more episodes of palpitations or syncope. LESSONS: Left ventricular noncompaction with right accessory pathway is a rare association with genetic basis and gives a higher risk of sudden cardiac death. Catheter ablation of the accessory pathway is a valuable way of treatment in this category of patients, lowering the risk of sudden cardiac death.

Takotsubo syndrome induced by malignant pheochromocytoma in a patient with type 2 papillary renal cell carcinoma - a case report.

The clinical presentation of the Takotsubo syndrome mimics an acute coronary syndrome with chest pain, ischemia-like ECG changes, mild to moderate myocardial enzyme elevation, and apical ballooning on echocardiography and ventriculography. On coronary angiography, epicardial coronary arteries are either normal or exhibit minimal atherosclerotic changes. Primary Takotsubo syndrome usually occurs in postmenopausal women in whom symptoms are triggered by emotional or physical stress, associated with catecholamine surges. Secondary Takotsubo syndrome may have multiple causes, including an increased catecholamine release due to pheochromocytoma. We present the case of a 56-years-old woman with confirmed Takotsubo syndrome who was later diagnosed with pheochromocytoma and type 2 papillary renal cell carcinoma.

Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles.

The issue of multidrug resistance (MDR) has become an increasing threat to public health. One alternative strategy against MDR bacteria would be to construct therapeutic vectors capable of physically damaging these microorganisms. Gold nanoparticles hold great promise for the development of such therapeutic agents, since the nanoparticles exhibit impressive properties, of which the most important is the ability to convert light into heat. This property has scientific significance since is exploited to develop nano-photothermal vectors to destroy bacteria at a molecular level. The present paper summarizes the latest advancements in the field of nanotargeted laser hyperthermia of MDR bacteria mediated by gold nanoparticles.

Selective ex vivo photothermal nano-therapy of solid liver tumors mediated by albumin conjugated gold nanoparticles.

We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of BSA bound to GNPs into tumor cells following ex-vivo intra-vascular perfusion.

Selective in vitro photothermal nano-therapy of MRSA infections mediated by IgG conjugated gold nanoparticles.

There are serious systemic infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and several other types of bacteria leading to the deaths of millions of people globally. This type of mortality is generally caused by the increasing number of antibiotic-resistant organisms, a consequence of evolution via natural selection. After the synthesis of gold nanoparticles (GNPs) by wet chemistry, bio-functionalization with IgG molecules was performed. Following administration of IgG-GNPs to MRSA cultures at various concentrations and various incubation time laser irradiation was performed. To assess the selectivity and specificity of the proposed treatment the following methods were used: flow cytometry, contrast phase microscopy, and by fluorescence microscopy. The results in our study indicate that following administration of IgG-GNPs biomolecule an extended and selective bacterial death occurs following laser irradiation in a dose dependent manner. Therefore, the new findings might impel studies on these antibacterial nanomaterials and their biological and medical applications.

High mass (>18g) of late gadolinium enhancement on CMR imaging is associated with major cardiac events on long-term outcome in patients with biopsy-proven extracardiac sarcoidosis.

BACKGROUND: Cardiac involvement is the most important cause of mortality in patients with systemic sarcoidosis. Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) has been shown to be a predictor of major cardiovascular adverse events (MACE) in the setting of systemic sarcoidosis. We sought to evaluate the relationship between LGE mass and adverse long-term outcome in patients with biopsy-proven extracardiac sarcoidosis. METHODS: Between 2001 and 2013, 197 consecutive patients with suspected cardiac sarcoidosis were identified in our institution database. Of them, 56 patients have had biopsy-proven extracardiac sarcoidosis and represented our studied population. Patients were divided into two groups based on LGE mass by a median value (mild LGE<18g, high LGE>18g) for comparison of MACE. RESULTS: Twenty-eight patients had a high mass of LGE. Of them, 15 (54%) experienced MACE (OR=31.15, 95% CI 3.7-262). Except for 1 patient, no patient with mild LGE presented with any MACE during follow-up (median of 32months). Patients with high LGE had lower CMR-derived left (53.6±14.9 vs. 62.2±6.7, p<0.01) and right (49.1±11.5 vs. 56.4±9.2, p<0.05) ventricular ejection fractions. LGE mass of 18g discriminated patients with and without MACE (93% sensitivity, 88% specificity, AUC=0.972). LGE mass was the only independent predictor of MACE on multivariate Cox analysis adjusted (OR=1.7, 95% CI 1.06 to 2.72, p=0.03). CONCLUSION: In biopsy-proven extracardiac sarcoidosis patients, a high mass of LGE >18g was associated with MACE.

Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin.

The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Right renal artery occlusion as a complication of fibromuscular dysplasia.

Renovascular hypertension is defined as elevated blood pressure levels due to the stenosis/ occlusion of the renal artery caused by fibromuscular dysplasia or atherosclerosis. We present the case of a 59-year old female patient with recently diagnosed arterial hypertension due to renal artery occlusion through intimal fibromuscular dysplasia. In this case, arterial blood pressure levels have not been controlled by maximum doses of antihypertensive drugs, used in association; rapid deterioration of the renal function, as well as important kidney damage, proven by imaging explorations, motivated the laparoscopic nephrectomy.

Lipoprotein (a) and lipid and non-lipid risk factors in coronaries risk assessment.

PURPOSE: Several studies showed that elevated plasma levels of lipoprotein(a) [Lp(a)] represent a predictor for cardiovascular risk. Based on already existing literature data, we aim to study the relationship between Lp(a), lipids and other cardiovascular risk factors in individuals with or without coronary heart disease. METHODS: We performed a cross-sectional transversal study on 208 patients (100 men and 108 women) aged between 37-75, with or without old myocardial infarction. In all the patients were evaluated the cardiovascular risk factors, the plasma level of the lipid fractions and Lp(a). The relationship between Lp(a) and the lipid and non-lipid risk factors were evaluated by the logistic regression method. RESULTS: The myocardial infarction group had higher values of plasma levels of Lp(a) (0.37 +/- 0.28 vs. 0.29 +/- 0.23 g/L, p < 0.05), and LDL-C (125.66 +/- 41.21 vs. 113.44 +/- 46.64 mg/dL, p < 0.05), than the group without coronary heart disease, as well as higher values of plasmatic TC/HDL-C ratio (4.31 +/- 1.55 vs. 4.08 +/- 1.29, p < 0.05), with significantly decreased plasmatic levels of HDL-C (45.88 +/- 12.04 vs. 53.22 +/- 23.12 mg/dL, p < 0.05). The association between the high Lp(a) plasma levels and the severity of coronary vessels number involved was significant. Multivariate analysis performed with adjustments for cardiovascular risk factors showed that the Lp(a), LDL-C and CT/HDL-C ratio levels are significant and independent predictive markers of coronary heart disease. CONCLUSION: The results show that the high Lp(a) plasma levels represent an independent cardiovascular risk factor, with superior risk prediction than the conventional lipid fractions. Our results confirm the Lp(a) as a marker for cardiovascular risk assessment in clinical practice.

Risk factors for heart failure in patients with one prior myocardial infarction episode.

BACKGROUND AND AIM: Myocardial infarction is an important risk factor for HF, increasing risk 2- to 3-fold. Other identified classical risk factors for HF include left ventricular hypertrophy, valvular heart disease, hypertension, diabetes mellitus, cigarette smoking, obesity, and dyslipidaemia. New mechanisms, such as insulin resistance, inflammation, and oxidative stress, have been investigated, but the importance of many of these mechanisms is largely unexplored in patients of HF. Our aim was to evaluate the factors involved in heart failure installation in patients with prior myocardial infarction. METHODS: We performed a cross-sectional study including 144 patients presenting old, certified myocardial infarction. Patients were divided into two groups according to presence/absence of heart failure, as certified by New York Heart Association (NYHA) classification of heart and of echocardiography criteria by left ventricular ejection fraction < 40%. Univariate and multivariate models were performed to identify the independent predictors of heart failure. Also, receiver operating characteristic analysis doubled by chi square test for trend was performed to analyze the risk impact of each identified predictor. RESULTS: Univariate between groups comparison was significant for hypertension (p = 0.001), diabetes mellitus (p < 0.001), smoking status (p < 0.001), obesity (p = 0.027), waist circumference (p < 0.001), and levels of C-reactive protein (p < 0.001), total cholesterol (p = 0.008), triglycerides (p = 0.003), HDL-Cholesterol (p < 0.001), glycaemia (p < 0.001) and brain natriuretic peptide (p < 0.001). Multivariate analysis selected C-reactive protein (OR = 2.7, 95% CI = 1.9-4.9, p < 0.001), glycaemia (OR = 2.1, 95% CI = 1.2-4.5, p = 0.027) and HDL-Cholesterol (OR = 0.7, 95% CI = 0.3-0.9, p = 0.035) as independent predictors. Separate across quintile test for trend revealed that the highest risk is added by levels of C-reactive protein levels > = 24mg/dL, followed by glycaemia levels > = 114 mg/dL and HDL-Cholesterol < 32 mg/dL. CONCLUSIONS: Reducing of C-reactive protein and glycaemia levels, as well as increasing the level of HDL-Cholesterol may add a great benefit in reducing heart failure installation risk in patients with myocardial infarction.

Survival prognostic factors in patients with resection of liver metastasis from colorectal cancer.

BACKGROUND AND AIM: Case selection criteria for resection of liver metastasis after colorectal cancer are still incompletely elucidated and represent a subject of great interest recently. Our aim was to evaluate 2-year survival after resection and to identify the survival risk and prediction factors in those cases. METHODS: 63 patients diagnosed and undergoing liver resection for colorectal metastatic disease to the liver at the Surgical University Hospital No.3 (Cluj-Napoca, Romania) between 01.01.2002 and 31.12.2005 were included in the study. Exclusion criteria were: palliative treatment as well as surgical treatment performed in a different surgical centre. After the surgical treatment, patients were followed regularly using clinical assessment on a 3 monthly basis with abdominopelvic ultrasound or computerised tomography annually. The following variables were recorded: age, gender, coexisting medical diseases, blood tests results, tumour site, maximal tumour diameter after resection, duration of surgery, surgical procedure and the clinical outcome until last follow-up, including date of death where appropriate. RESULTS: 2-year post-operative survival was 65.1%. In univariate analysis: age (< 65 vs > = 65 years, p = 0.041), metastasis number (< 3 vs > = 3 tumors, p = 0.049), maximal tumor dimension (< 3 vs > = 3 cm, p = 0.047), glutamine-oxaloacetic transaminase (GOT) preoperative level (< 42 vs > = 42 mg/dl, p = 0.018) were significant factors correlated to median survival time. However, non of the above mentioned factors presented independent prediction power in multivariate analysis (Cox regression, p < 0.05). CONCLUSIONS: Our results support liver metastasis resection without prior case selection except for technically-operative criteria selection.