The Added Value of Advanced Echocardiography for the Morpho-Functional and Prognostic Evaluation of the Right Heart in Dilated Cardiomyopathy: Do Not Forget about the Right Atrium.

(1) Introduction and Aims: Right ventricular (RV) remodeling significantly impacts the prognosis of dilated cardiomyopathy (DCM) patients, and right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to (i) evaluate right heart subclinical changes and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM by advanced echocardiography. (2) Materials and Methods: Sixty-eight patients with DCM (with a mean age of 60 years; 35 men) were evaluated by comprehensive transthoracic echocardiography, compared to 62 age- and sex-matched healthy controls (with a mean age of 61 years; 32 men), and followed up for 12.4 ± 5 months. (3) Results: DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, higher RA minimum volumes and tricuspid annulus areas despite having normal RV volumes, ejection fractions, and RA maximum volumes by 3DE compared to the controls. The RA strain and RV strain are correlated with each other. The RA reservoir strain (with an AUC = 0.769) has an increased value for outcome prediction compared to that of the LA strain. (4) Conclusion: Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and the RA strain is associated with an increased risk of hospitalization and cardiac death.

Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer.

(1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter (p = 0.0371), with a deeper degree of tumor invasion T3-4 (p = 0.0159), invasion in more than two lymph nodes (p = 0.0462), or a TNM stage III-IV. Regarding the survival analysis, better survival rates (65%) were observed for patients with a low value of beta 2 adrenoreceptors (B2A-), compared to B2A (+) patients, in which survival at 3 years of follow-up was only 43%. In addition, the analysis of intra-tumoral sympathetic fibers showed a better survival rate (83%) for patients with a low value of density compared to patients with increased density, in whom the survival rate was only 24%. (4) Conclusions: The findings of this study indicate that patients with stomach cancer have a more unfavorable prognosis when they have a higher density of sympathetic nerve fibers and an increased expression of beta 2 adrenergic receptors inside the tumor.

Chitosan Versus Dapagliflozin in a Diabetic Cardiomyopathy Mouse Model.

Diabetes mellitus is a metabolic disorder with global economic implications that can lead to complications such as diabetic cardiomyopathy. The aim of this study was to compare the effects of chitosan versus dapagliflozin in mouse diabetic cardiomyopathy. We used 32 C57Bl/6 male mice aged between 8 and 10 weeks, which were randomly divided into Control-without diabetes mellitus (DM), type 1 DM (T1DM), T1DM + Chitosan, and T1DM + Dapapgliflozin groups. We induced diabetes with streptozotocin and treated the animals for 12 weeks. The analysis showed a reduction in intramyocardial fibrosis in the T1DM + Dapapgliflozin compared to T1DM animals. In T1DM + CHIT, a reduction in intramyocardial fibrosis was observed although, accordingly, there was also no significant decrease in blood glucose. The level of oxidative stress was reduced in the groups of treated animals compared to T1DM. All these observed changes in the structure and function of hearts were highlighted in the echocardiographic examination. In the treated groups, there was delayed appearance of left ventricular (LV) hypertrophy, a slight decrease in the ejection fraction of the LV, and an improved diastolic profile. The results demonstrate that chitosan has promising effects on diabetic cardiomyopathy that are comparable to the beneficial effects of dapagliflozin.

Predictors for Super-Responders in Cardiac Resynchronization Therapy.

BACKGROUND: Prediction of cardiac resynchronization therapy (CRT) response, particularly a super-response, is of great importance. STUDY QUESTION: The aim of our study was to assess the predictors for super-responders in CRT. STUDY DESIGN: We conducted a retrospective, observational study, which finally included 622 patients with heart failure treated with CRT between January 2008 and May 2020 who had a minimal follow-up of 6 months after CRT. MEASURES AND OUTCOMES: A total of 192 super-responders, defined by a left ventricular ejection fraction (LVEF) of at least 45%, and/or minimum 15% increase in LVEF and an improvement of the New York Heart Association functional class by at least 2 degrees at the last follow-up, and the rest of 430 patients who did not fulfill the super-responder criteria. RESULTS: The highest rate of super-responders (41.91%, n = 171) was at patients with left ventricle-only pacing with optimal fusion (OPT) compared with patients with biventricular (BiV) pacing (9.81%, n = 21, P < 0.000). In the OPT group, univariable analysis showed that nonischemic cardiomyopathy, a smaller degree of mitral regurgitation, and better left ventricle function at enrollment were predictors for super-response compared with the BiV group where a narrower QRS after implantation, nonischemic cardiomyopathy, and a better baseline LVEF were predictors for super-responders. In the multivariable analysis, both narrower QRS after implantation and nonischemic cardiomyopathy were independent predictors for super-response in the BiV group compared with OPT where nonischemic cardiomyopathy remained the only independent predictor for super-response. CONCLUSIONS: In this retrospective study, OPT CRT programing was an additional predictor of super-response to CRT besides nonischemic cardiomyopathy.

Dapagliflozin Ameliorates Neural Damage in the Heart and Kidney of Diabetic Mice.

(1) Background: Measures for the control of diabetes mellitus (DM) and, especially, for the control of its complications represent a main objective of the research carried out on this disease, since both mortality and morbidity relating to DM represent real problems for the health system worldwide. The aim of our study was to evaluate nervous tissue from the heart and kidneys of mice with diabetes induced by streptozotocin (STZ) in the presence or absence of dapagliflozin (DAPA) treatment. (2) Methods: For this purpose, we used 24 C 57Bl/6 male mice, aged between 8 and 10 weeks. The mice were divided into three groups: sham (DM-), control (DM+), and treated (DM+). Diabetes mellitus was induced by injecting a single intraperitoneal dose of STZ. The duration of diabetes in the mice included in our study was 12 weeks after STZ administration; then, the heart and kidneys were sampled, and nervous tissue (using the primary antibody PGP 9.5) from the whole heart, from the atrioventricular node, and from the kidneys was analyzed. (3) Results: The density of nerve tissue registered a significant decrease in animals from the control group (DM+), to a value of 0.0122 ± 0.005 mm2 nerve tissue/mm2 cardiac tissue, compared with the sham group (DM-), wherein the value was 0.022 ± 0.006 mm2 nervous tissue/mm2 cardiac tissue (p = 0.004). Treatment with dapagliflozin reduced the nerve tissue damage in the treated (DM+DAPA) group of animals, resulting in a nerve tissue density of 0.019 ± 0.004 mm2 nerve tissue/mm2 cardiac tissue; a statistically significant difference was noted between the control (DM+) and treated (DM+DAPA) groups (p = 0.046). The same trends of improvement in nerve fiber damage in DM after treatment with DAPA were observed both in the atrioventricular node and in the kidneys. (4) Conclusions. These data suggest that dapagliflozin, when used in streptozotocin-induced diabetes in mice, reduces the alteration of the nervous system in the kidneys and in the heart, thus highlighting better preservation of cardiac and renal homeostasis, independent of any reduction in the effects of hyperglycemia produced in this disease.

Remote Monitoring in Cardiac Resynchronization Therapy-First Experience in Romania with a CRT Virtual Ward.

BACKGROUND: Remote monitoring (RM) is becoming a standard of care for patients with cardiac resynchronization therapy (CRT). This technology combines the use of pacemakers or implantable cardioverter-defibrillators (ICD) and wireless communication to provide physicians with continuous, real-time information on the patient's cardiac activity. The purpose of the study was to evaluate if the remote monitoring technology in the follow-up CRT patients is feasible and safe. METHODS: A total of nine patients were enrolled in the study, implanted with a CRT system with wireless transmission capabilities. Immediately after the procedure received the RM, were enrolled in the virtual clinic and instructed by the doctor how to use the device at home. Regular virtual transmissions were made automatically every 3 weeks, respecting optimal transmission conditions. The accumulation of fluid in the lungs, atrial or ventricular tachyarrhythmia together with system integrity automatically activate alerts. RESULTS: One hundred and one transmissions were collected and analyzed from the virtual ward. Average follow-up was 7.7±4.8 months, longest follow-up was 18 months. None of the patients experienced complications during the study period, with three of them being follow-up solely through telemetric means by implanting physician. Treatment optimization was successfully conducted via phone consultations, when necessary, without any adverse events. CONCLUSIONS: The results of our study suggest that RM could be integrated into routine CRT management protocols, enhancing patients care and resource utilization.

The Assessment of Heart Rate Variability in Patients with Pancreatic Cancer.

The aim of our study is to provide an assessment of heart rate variability (HRV) as a predictor for the survival of patients with pancreatic cancer (PCa). We conducted a retrospective, descriptive study. 53 consecutive patients who were newly diagnosed with pancreatic cancer (PCa), were included. In the end, 41 patients were included in the analysis, out of which 14 patients survived at least until the 24-month follow-up, while 27 patients died within 24 months from the diagnosis. These patients were monitored with 24-hour Holter electrocardiogram (ECG) prior to the initiation of any therapy for determining heart rate variability. To establish the cut-off values of HRV, 24-hour Holter ECG recordings of 20 healthy subjects were analyzed. In addition to heart rate analysis, HRV indices were also analyzed: SDNN, rMSSD, ULF and VLF. Median survival in patients with low value of SDNN was 9 months, compared to patients with hight SDNN where median survival was 15 months (Hazard ratio 2.301, 95% CI of ratio 0.9080 to 5.833, p= 0.034). Although low values of the HRV indices in the frequency domain were associated with reduced survival, no statistically significant differences were recorded. The reduction of heart rate variability indices is a negative prognostic factor in patients newly diagnosed with pancreatic cancer.

Update in LV Only Fusion CRT Pacing: Annals and Future Perspectives.

Triple-chamber cardiac devices are utilized for cardiac resynchronization therapy (CRT) and is the standard-of-care therapy for heart failure (HF) patients in the current guidelines. In the setting of biventricular (BIV) pacing it involves a mandatory implantation of right ventricular (RV) lead that allows simultaneous BIV pacing with 0 ms VV (ventricular to ventricular) interval. Nevertheless, it seems that response to CRT is not related to RV lead position. RV pacing is known for deleterious effects on RV/Left Ventricle (LV) function and should not be used in persons with normal atrioventricular conduction (AV) and sinus rhythm. As it compensates for the additional asynchrony induced by unnecessary stimulation of RV pacing, only pacing the left ventricle (LV) may result in improved cardiac resynchronization therapy (CRT) outcomes and a decrease in the number of individuals who do not respond to the procedure. Furthermore, leadless LV fusion CRT pacing without RV lead could be a potential CRT therapy alternative to BIV pacing in nonischemic heart failure patients with preserved AV conduction. The aim of our study is to made an update in cardiac resynchronization therapy with LV only fusion pacing.

Contribution of Modern Echocardiographic Techniques in the Detection of Subclinical Heart Dysfunction in Young Adults with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease affects about 30% of the population and it has a growing tendecy with the increasing incidence of obesity. Currently, a large amount of clinical evidence has shown that cardiovascular disease represents the main cause of mortality in patients suffering from non-alcoholic fatty liver disease. OBJECTIVE: In this study we investigated the structural and functional changes of the left ventricle in young adults with hepatic steatosis using modern echocardiographic techniques. METHODS: By using tissue Doppler imaging and also Speckle tracking echocardiography the left ventricle systolic function was assessed. RESULTS: All patients included in the study had a normal left ventricular ejection fraction but, when the longitudinal function of the left ventricle was assessed using the tissue Doppler technique (maximum systolic velocity S) statistically significant differences were found in both the group of patients with non-alcoholic fatty liver as well as in the group of patients associated with diabetes. Using speckle tracking echocardiography, we found a statistically significant decrease of the global longitudinal strain in the endocardium, in the group of patients with non-alcoholic liver disease but also in the group of those with diabetes. The overall longitudinal strain at the myocardium was significantly reduced only in the group of patients with non-alcoholic fatty liver disease and diabetes, while the overall longitudinal strain at the epicardium showed no changes in any of the groups studied. Also, no changes were observed at the circumferential strain. CONCLUSION: Non-alcoholic fatty liver disease, diagnosed in asymptomatic young adults may be a risk factor for remodeling the left ventricle over time, being associated with subclinical myocardial dysfunction, regardless of the presence of other cardiovascular risk factors.

Automated left atrial volume measurement by two-dimensional speckle-tracking echocardiography: feasibility, accuracy, and reproducibility.

AIMS: A byproduct of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Accordingly, we sought to (i) assess the feasibility of automated LAVmax measurement by 2DSTE; (ii) compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and (iii) evaluate the accuracy and reproducibility of the three echocardiography techniques. METHODS AND RESULTS: LAVmax (34-197 mL) were obtained from 198/210 (feasibility 94%) consecutive patients (median age 67 years, 126 men) by 2DSTE, 2DE, and 3DE. 2DE and 2DSTE measurements resulted in similar LAVmax values [bias = 1.5 mL, limits of agreement (LOA) ± 7.5 mL], and slightly underestimated 3DE LAVmax (biases = -5 mL, LOA ± 17 mL and -6 mL, LOA ± 16 mL, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r = 0.946 and r = 0.935, respectively; P < 0.001). However, LAVmax obtained by 2DSTE (bias = -9.5 mL, LOA ± 16 mL) and 2DE (bias = -8 mL, LOA ± 17 mL) were significantly smaller than those measured by CMR. Conversely, 3DE LAVmax were similar to CMR (bias = -2 mL, LOA ± 10 mL). Excellent intra- and inter-observer intraclass correlations were found for 3DE (0.995 and 0.995), 2DE (0.990 and 0.988), and 2DSTE (0.990 and 0.989). CONCLUSION: Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax.

Assessment of Left Ventricular Diastolic Function in Young Adults with Nonalcoholic Fatty Liver Disease.

There is strong evidence that, in addition to increasing the risk of cirrhosis as well as hepatocellular carcinoma, nonalcoholic liver disease represents an independent risk factor for different diseases including cardiovascular and chronic kidney disease and also type 2 diabetes. OBJECTIVE: to assess whether nonalcoholic fatty liver disease is associated with diastolic dysfunction of the left ventricle, independent of other classic risk factors. METHODS: we included 79 patients aged 15-45, diagnosed with non-alcoholic liver disease, and a group of 80 healthy people in the same age group. We assessed left ventricular diastolic function using Doppler pulsed wave transmitral flow and Tissue Doppler Imaging methods. RESULTS: there were lower velocities of E and e' wave, a decrease in E/A ratio and an increase in E/e' ratio in the group of patients with hepatic steatosis and in those with associated diabetes compared to the control group, but not the same was observed when comparing patients with steatosis alone vs. hepatic steatosis and associated diabetes mellitus. CONCLUSION: nonalcoholic steatosis is linked to echocardiographic features of early diastolic dysfunction that are present in patients suffering from diabetes.

The Prognostic Correlation of Heart Rate Variability at Diagnosis with Survival of Patients with Hepatocellular Carcinoma.

BACKGROUND: Heart rate variability (HRV) indices have been shown to be associated with prognosis in various types of cancer. This study aims to assess the ability of these indices to predict survival in hepatocellular carcinoma (HCC) patients after diagnosis. METHODS: We retrospectively collected data from 231 patients diagnosed with HCC between January 2014 and March 2018. The baseline clinical-pathological variables and HRV indices (extracted from Holter electrocardiogram recordings) were analyzed. RESULTS: Univariate and multivariate analyses were performed to identify the predictive value of the above factors for overall survival (OS). The univariate analysis revealed that an age > 60 years, hepatitis C, portal vein involvement (thrombosis), a tumor size > 5 cm, alpha-fetoprotein (AFP) > 400 ng/mL, serum albumin, and C-reactive protein (CRP) were risk factors for poor OS. Multivariable Cox regression analyses identified that a tumor size > 5 cm and AFP > 400 ng/mL predict poorer outcomes in HCC patients. It should be mentioned that, in both the univariate analysis and in the multivariate analysis, between HRV indices, SDNN (standard deviation of all normal-to-normal (NN) intervals) < 110 ms was an independent risk factor for OS with an HR of 3.646 (95% CI 2.143 to 6.205). CONCLUSION: This study demonstrates that HRV indices identify HCC patients at high risk of death and suggests that such monitoring might guide the need for early therapy in these types of patients, as well as the fact that HRV can be a potential noninvasive biomarker for HCC prognosis.

Assessment of Epinephrine and Norepinephrine in Gastric Carcinoma.

The aim of our study was to assess the sympathetic nervous system's involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system's activity predicts increased gastric carcinoma severity.

The Neuroprotective Role of Alpha Thioctic Acid and Vitamin B Complex in Diabetic Neuropathy - an Experimental Study.

Worldwide, approximately 463 million people are estimated to suffer from a form of diabetes mellitus, with diabetic neuropathy being one of its most common complication. Using streptozotocin to induce diabetes in C57BL/6J mice, we assess the neuroprotective role of alpha thioctic acid and vitamin B complex in diabetic neuropathy. In order to highlight the peripheral nerve changes produced by diabetes, we performed an electroneurographic recording of the animals and compared the amplitude of the compound muscle action potential (CMAP). Treatment with alpha thioctic acid (A), or vitamin B complex (B), or A+B caused a smaller decrease in CMAP amplitude than if these therapies had not been applied. On the other hand, we found that in group A+B a smaller decrease of CMAP amplitude was observed compared to the control group (6 weeks after the onset of diabetes p<0.0001). Also, separate treatment with alpha thioctic acid alone caused a smaller decrease in CMAP amplitude compared to the control group (6 weeks after the onset of diabetes mellitus p<0.0436), but also separate treatment with vitamin B complex alone resulted in a smaller decrease of CMAP amplitude compared to the Control group (6 weeks after the onset of diabetes p<0.0070). The combined therapy with alpha thioctic acid and vitamin B complex has a greater effect in preventing axonal degeneration in diabetic neuropathy than the single therapy only with alpha thioctic acid or only with vitamin B complex.

Alpha-lipoic acid and vitamin B complex slow down the changes in mice diabetic cardiomyopathy.

AIM: The aim of our study was to assess histologically and by cardiac ultrasound the effects of alpha-lipoic acid (ALA) and vitamin B complex, as pathogenic therapies, in diabetic cardiomyopathy (DCM) in mice. MATERIALS AND METHODS: We performed an experimental animal study, in which we analyzed from a structural and functional point of view the changes produced in DCM. To produce DCM, we induced diabetes mellitus (DM) in C57BL∕6 mice by intraperitoneal injection of a single 150 mg∕kg body weight dose of streptozotocin (STZ). We formed a sham group (animals without DM), a control group (animals with DM but without treatment, DM_Control) and a group of animals with DM that were treated with ALA and vitamin B complex (DM_Treated). RESULTS: At six weeks after STZ administration, there was no decrease in left ventricular ejection fraction (LVEF) in the sham group, while in the control group there was a significant decrease in LVEF, about 43.75±3.37%, compared to the group that received treatment with ALA and vitamin B complex, in which LVEF decreased to 49.6±5.02% (p=0.0432). Also, the degree of interstitial myocardial fibrosis was higher in animals with DM compared to animals without DM, but the applied therapeutic protocol considerably improved the accumulation of interstitial collagen. The same observation was maintained regarding the evaluation of polysaccharide deposits. CONCLUSIONS: We can say that the administration of ALA and vitamin B complex in mice with STZ-induced DM, improves the degree of myocardial fibrosis, the accumulation of polysaccharides, and prevents severe deterioration of systolic and diastolic function of the heart.

NT-proBNP and Echocardiographic Parameters in Liver Cirrhosis - Correlations with Disease Severity.

determined. Liver disease severity in patients with cirrhosis was established by Child-Pugh class, MELD score and presence/absence of ascites. Results: Plasma levels of NT-proBNP were significantly higher in cirrhotic patients than in the healthy subjects. NT-proBNP levels were also significantly elevated in Child-Pugh class C patients compared to those in class B and A. Left atrium size, diastolic function, left ventricular wall thickness and left ventricular ejection fraction were significantly altered in cirrhotic patients compared to controls. Advanced cirrhosis and high levels of NT-proBNP were significantly associated with increased left atrium volume and signs of cardiac diastolic dysfunction. We also observed significant differences between quartile groups of MELD score for the following: NT-proBNP, Troponin I, left atrium volume, left ventricle wall thickness, lateral wall and septum systolic tissue doppler velocities and global longitudinal strain. Conclusion: NT-proBNP is increased in patients with cirrhosis and is correlated with the severity of liver disease as established by Child-Pugh class, MELD score and presence of ascites.

B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma.

AIM: To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer. METHODS: In this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni's post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson's correlation coefficient. RESULTS: B2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses. CONCLUSION: B2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.

Synaptophysin expression as prognostic factor for survival in colorectal carcinomas.

The aim of this study is to assess the status of synapses in normal colorectal tissue compared to neoplastic colorectal tissue, and to correlate this status with survival in patients with colorectal neoplasia. Our study included 61 patients diagnosed with colorectal adenocarcinoma, representing the study group, and 53 patients diagnosed with benign conditions, that required a resection of a colorectal segment, representing the control group. We performed the immunohistochemical staining by using anti-synaptophysin antibody, which identifies synaptic vesicles and, so, we managed to analyze the expression of synapses in colorectal adenocarcinoma. Regarding both the signal area and integrated optical density (IOD) of the synaptophysin, the univariate analysis with a log-rank (Mantel-Cox) test indicated that patients with a low level of synaptophysin had a better overall survival rate than those with a high-level synaptophysin. Also, we noticed that tumor size, tumor invasion and lymph node metastasis were significantly associated with the overall survival rate, whereas the other clinicopathological features were not. In conclusion, the status of synaptic vesicles evaluated via synaptophysin expression in patients with colorectal cancer positively correlates with the survival rate and it can play a role in the neoplastic therapy process.

Neuro-neoplastic interrelationships in colorectal level - immunohistochemical aspect in three cases and review of the literature.

Colorectal cancer represents a severe public health issue. Recent studies have shown the essential role played by nerves and their neurotransmitters in tumor initiation and progression. The aim of this study is to asses the expression of beta 2-adrenergic receptors (ß2A) for adrenaline and noradrenaline, and the expression of M3 muscarinic receptors (M3R) for acetylcholine (neurotransmitters produced and released by sympathetic and parasympathetic afferents of the digestive tract and also by the enteric nervous system) in different tumor gradings of colorectal adenocarcinoma, and also the tropomyosin receptor kinase A (TrkA) for the nerve growth factor produced by the cells of colorectal adenocarcinoma. Beta 2-adrenergic receptors were expressed both in normal colic tissue and in the tumor tissues, from the three patients included in the study. It was observed that both area and integrated optical density (IOD) are more elevated for this type of receptor in tumor tissues than in normal colic tissue. For the M3 muscarinic receptors, similarly to beta 2-adrenergic receptors, it was observed a growth both of the area and of the IOD with the tumor grading. The presence of TrkA receptors was also observed both in the normal colic mucosa and in the tumor tissues examined, but with a significant reduction of the signal in the poorly differentiated tumor tissue. Understanding the neurobiology of cancer in this context becomes necessary for establishing much more complex and targeted molecular targeted therapies.

From molecular mechanism to morphological changes in cardiomyopathy.

The aim of this study is to make a foray in the world of constitutive elements of the architectural and functional organizing of the cardiomyocytes involved in cardiomyopathies and of the genetic molecules that they express. Primary cardiomyopathies represent a group of diseases characterized by primary structural and functional changes of the myocardium, without myocardial ischemic disease, hypertension, valvulopathies or congenital cardiac diseases being involved. In the pathogenesis of the cardiomyopathies proteins, especially from the sarcomere, Z-disc, cellular cytoskeleton, sarcolemma, intercalated discs, nuclear envelope and other constitutive proteins of the cardiomyocytes are involved. Deciphering of these pathophysiological mechanisms is part of the new model of personalized medicine, and it is useful in developing and in the optimization of new strategies for the management of the patients diagnosed with this type of disease.