Elderly Individuals Residing in Nursing Homes in Western Romania Who Have Been Diagnosed with Hearing Loss are at a Higher Risk of Experiencing Cognitive Impairment.

Purpose: The objective of this research was to determine if there is any correlation between the severity of neurocognitive disorder and hearing impairment in the elderly. Patients and Methods: This is a population-based observational study that included subjects aged ≥ 65 years. They were evaluated for the existence of cardiovascular risk factors, diabetes, stroke, alcohol abuse, and smoking. Hearing impairment was diagnosed by an audiologist, using behavioral audiometric examination. These evaluations might have been performed in response to concerns about hearing loss, or they could have been a routine component of yearly comprehensive health screenings that included a Mini-Mental State Examination 2nd Edition (MMSE-2) test. According to the results of the MMSE-2 scale, we divided the individuals into two groups, Group I for those who had cognitive impairment and severe neurocognitive disorder, and Group II for those who did not have cognitive impairment. Results: The study enrolled 203 patients with a mean age of 77 ± 7.5 years (range 65-98), 99 (48%) were males. When comparing the two groups, group I patients presented more often cardiovascular risk factors, stroke, diabetes, and impaired hearing. The univariable logistic regression found that cognitive impairment was significantly more frequent in the elderly with cardiovascular disease, diabetes, and stroke (p<0.0001). The multivariate regression analysis found that stroke (p<0.0001) diabetes (p=0.0008), cardiovascular disease (p=0.0004), and impaired hearing (p=0.0011) were significantly linked to cognitive impairment. The occurrence of hearing impairment in the elderly was related to having an MMSE-2 score of 14 or below. Conclusion: According to the findings of this research, the elderly who have trouble hearing in addition to other conditions might have an increased risk for severe neurocognitive disorder.

Subtle Changes in Myocardial Work Indices Assessed by 2D-Speckle Tracking Echocardiography Are Linked with Pathological LV Remodeling and MACEs Following an Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling (p < 0.0001). During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers (p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.

Increased Left Atrial Stiffness is Significantly Associated with Paroxysmal Atrial Fibrillation in Diabetic Patients.

Purpose: Atrial fibrillation (AF) and diabetes mellitus (DM) are common pathogenic diseases. Diabetes is an independent risk factor for AF, and coexisting AF is a risk factor for the diabetic pa-tient's progression. The purpose of this study was to see if two-dimensional-speckle tracking echocardiography (2D-STE) might provide valuable criteria for determining the risk of AF in diabetic patients. Patients and Methods: This retrospective study compared 30 adult diabetic patients with documented paroxysmal atrial fibrillation (PAF) with 30 age- and sex-matched diabetic patients without PAF. Inclusion criteria were: age ≥18 years, sinus rhythm, diabetes mellitus type 2, and the ability to sign the informed consent. Exclusion criteria included: moderate or severe valvular disease, previous myocardial infarction, left ventricular ejection fraction (LVEF) <50%, congenital heart disease, a history of cardiac surgery, paced atrial or ventricular rhythm, inadequate echocardiography imaging. The medical history, clinical, biochemical data and the results of the transthoracic cardiac ultrasound examination were registered during their evaluation at the outpatients cardiology clinics. Results: The mean age of the patients was 62.5±1.7 years, 60% were men. Diabetic patients who experienced PAF episodes demonstrated significantly impaired left atrial (LA) deformation patterns, with decreased LA strains and increased LA stiffness (p < 0.05). Conclusion: The present study demonstrates that LA strains and LA stiffness are significantly associated with the occurrence of PAF in diabetic patients. As 2D-STE of the LA is more sensitive than routine echocardiographic examination, it should be performed in patients suspected of being suffering from PAF.

Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells.

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen's eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

Left Ventricular Remodeling Risk Predicted by Two-Dimensional Speckle Tracking Echocardiography in Acute Myocardial Infarction Patients with Midrange or Preserved Ejection Fraction in Western Romania.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk for left ventricular (LV) remodeling and heart failure. We aimed to study whether LV strains (S) and strain rates (SR) could predict cardiac remodeling in patients with AMI having a midrange or preserved LV ejection fraction (EF) following a percutaneous coronary intervention (PCI) within the first 12 hours from the onset of symptoms. PATIENTS AND METHODS: This is a case-control observational study including patients admitted for their first AMI, either with ST-segment elevation (STEMI) or without ST elevation (NSTEMI), with an LVEF > 40% after a successful PCI. Echocardiography was repeated after 6 months, and the patients were divided into two groups, according to whether LV remodeling was determined on echocardiography. RESULTS: Of the 253 AMI patients (mean 66 aged ± 13 years), including 185 males (73%), 61 (24%) presented signs of LV remodeling. In univariate logistic regression analysis, age, male sex, smoking history, hypertension, hypercholesterolemia, Killip class, renal function, peak creatine phosphokinase - MB level, 2- and 3-vessel coronary artery disease (CAD), and several echocardiographic parameters were significantly associated with LV remodeling (P<0.05). In multivariate logistic regression analysis harmed (H) LS and SR, Killip class, 3-vessel CAD, and LV end-diastolic volume were outlined as independent predictors for LV remodeling. Receiver operating characteristic curve analyses showed that HLS and HLSR were the most powerful independent predictors for LV remodeling (P<0.001), with an area under the curve (AUC) of 0.85 (sensitivity 83%; specificity 84%; p <0.001) and 0.77 (sensitivity 93; specificity 61%; p <0.001), respectively. The identified cut-off values for predictor variables were HLS< -11%, and HLSR< -0.65s-1. CONCLUSION: We concluded that 2D-STE was the best method to evaluate LV remodeling in patients with AMI and midrange or preserved LVEF following myocardial revascularization by a PCI.

Toll-like receptor 4 (TLR4) expression is correlated with T2* iron deposition in response to doxorubicin treatment: cardiotoxicity risk assessment.

Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient's chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051-0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r = - 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).

The Predictive Value of Endothelial Inflammatory Markers in the Onset of Schizophrenia.

PURPOSE: This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment. PATIENTS AND METHODS: The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone. RESULTS: The average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P<0.0001), and increased after treatment (P=0.02), but remained lower than in the healthy controls (P=0.026). The initial levels of sVCAM-1 levels were higher in the patients (P<0.0001) and decreased after treatment (P<0.0001) to values that were similar to those of the control group (P=0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level (P<0.0001). Antipsychotic treatment induced significant decreases in BPRS score (P<0.0001), in systolic (P=0.005) and diastolic (P<0.0001) blood pressure, in HDL-c (P=0.02), as well as significant increases in blood glucose (P<0.01) and LDL-c (P<0.001), with no differences between olanzapine and risperidone. CONCLUSION: In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline.

Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer.

PURPOSE: The aim of this study was to assess whether nebivolol treatment could have beneficial effects in the prevention of anthracyclines-induced cardiotoxicity. PATIENTS AND METHODS: Our prospective study included 60 women, mean age 52.6±13 years, with HER2 negative breast cancer, scheduled to undergo treatment with doxorubicin. The patients were randomly divided into two groups: the treatment group (n=30) which received nebivolol 5 mg once daily for the duration of chemotherapy and the control group (n=30) without treatment with nebivolol. Cytostatic treatment was performed with doxorubicin 70 mg/m2 administered intravenously every 21 days for six cycles. The average cumulative dose of doxorubicin was 520±8 mg/m2. Echocardiography was performed immediately before and after six cycles of doxorubicin therapy. RESULTS: We found no significant differences between the two groups regarding baseline clinical and echocardiographic parameters. The two groups reached a similar cumulative dose of doxorubicin. No patient died during the study. None of the patients withdrew from chemotherapy. After six cycles of doxorubicin therapy, the left ventricular (LV) ejection fraction, shortening fraction, and LV diameters changed, but not significantly. Tissue Doppler imaging (TDI) detected in the control group a significant decrease of myocardial velocities, indicating a LV diastolic dysfunction. In the same group, speckle tracking imaging (STI) revealed a statistically significant alteration of the ventricular deformation, which means a decrease in LV systolic function. In the nebivolol treatment group, no significant alterations in the LV systolic and diastolic function were observed. CONCLUSION: The results of this study show the benefit of new echocardiographic imaging methods such as TDI and STI in the screening of early cardiac dysfunction induced by cytostatic treatment. Nebivolol treatment prevented the occurrence of anthracyclines-induced cardiomyopathy in the short term. In order to confirm these preliminary results, larger studies with a longer follow-up period are required.

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Rates and predictors of uncontrolled bronchial asthma in elderly patients from western Romania.

PURPOSE: Bronchial asthma (BA) is a chronic inflammatory disorder of the airways, featuring variable and often reversible airflow limitations. An accurate assessment of BA control is difficult in practice, especially in the elderly, requiring the assessment of several clinical and paraclinical parameters that are influenced not only by asthma, but also by comorbidities. The purpose of this study was to evaluate the predictors of uncontrolled BA in a group of elderly patients from western Romania. PATIENTS AND METHODS: We retrospectively evaluated 126 elderly patients (aged $ 65 years), who were consecutively evaluated in the Pulmonology Department of Victor Babes Hospital, Timisoara, Romania, between March 2009 and July 2012. We collected demographic data, performed pulmonary function testing and an asthma control test (ACT), and evaluated the level of BA control based on the 2012 Global Initiative for Asthma guidelines. Statistical processing of the data was done using the Epi Info and STATA programs. RESULTS: In our study group, 36 (29%) patients were men and 90 (71%) were women; their mean age was 74.42±8.32 years (range: 65-85 years). A total of 14.28% of patients were smokers. About 30.15% of patients had an ACT score <19, 54.76% had an ACT score 20-24, and 15.09% had an ACT of 25. Moreover, 59.52% had normal spirometry results. Infectious exacerbations were found in 58.73% of patients. A history of allergies was demonstrated in 48.41% of patients, 34.12% had occupational exposure, and 82.53% of patients were treated with inhaled corticosteroids. Our results showed that 30.15% of patients had uncontrolled BA. We found six predictive factors for uncontrolled BA: infectious exacerbation, occupational exposure, mixed (obstructive and restrictive) ventilatory dysfunction, persistent airway obstruction on spirometry, duration of disease in months, and current smoking status. Infectious exacerbations, persistent airway obstructions, and occupational exposure were the most powerful predictors. CONCLUSION: Elderly patients represent an important group that is at risk for developing uncontrolled BA. Predictors may identify those elderly patients with uncontrolled BA and facilitate early medical interventions.

Causes and predictors of hospital readmissions in patients older than 65 years hospitalized for heart failure with preserved left ventricular ejection fraction in western Romania.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is more frequent in the elderly and is associated with important economic implications because of repetitive and prolonged hospitalizations, due to both cardiovascular and noncardiovascular causes. PURPOSE: To identify the causes, as well as the clinical and biological markers, that could be used as predictors of hospital readmissions in HFpEF patients aged ≥65 years. PATIENTS AND METHODS: Consecutive eligible patients hospitalized for a first heart failure (HF) episode were prospectively included and divided into one of two age groups (elderly: ≥65 years; and nonelderly: <65 years). The clinical features, therapeutic approaches, and clinical outcomes during the 1-year follow-up period were analyzed. RESULTS: A total of 178 patients were included, with a mean age of 64.6±8.6 years; 80 (45%) were women. A total of 98 patients (55%) were aged ≥65 years, and 80 (45%) were aged <65 years. In the group aged ≥65 years, 58 patients (59%) were women, while in the group aged <65 years, 22 patients (28%) were women (P=0.0001). During the 1-year follow-up, no patients died or were lost to follow-up. Moreover, 116 (65%) of the HFpEF patients experienced hospital readmissions. The elderly patients had a significantly higher readmission rate (73% vs 55%, respectively; P<0.02); readmissions due to aggravated HF were significantly more frequent in this age group (41% vs 18%, respectively; P<0.002). Multivariate logistic regression analysis indicated that the independent predictors of readmission due to HF aggravation included plasma levels of brain natriuretic peptide >450 pg/mL (P<0.01) and N-terminal-pro-brain natriuretic peptide >477 pg/mL (P<0.02) in the elderly group, while in the nonelderly group, the independent predictors of this outcome were a New York Heart Association functional class of IV at initial hospitalization (P<0.04), as well as plasma levels of brain natriuretic peptide >390 pg/mL (P=0.03) and tumor necrosis factor (TNF)-α >7.1 pg/mL (P<0.001). Readmissions due to noncardiovascular causes were independently predicted by plasma levels of TNF-α >10 pg/mL in the elderly (P=0.003) and of interleukin (IL)-6 >1.9 pg/mL in the nonelderly (P<0.04). CONCLUSION: We conclude that in HFpEF patients aged ≥65 years, the main cause of rehospitalization during the 1-year follow-up was HF aggravation. The risk of this outcome was independently predicted by increased levels of cardiac peptides, while the risk of noncardiovascular readmissions was predicted by increased levels of inflammatory biomarkers. Increased TNF-α levels predicted both cardiovascular and noncardiovascular readmissions, while increased levels of high-sensitivity C-reactive protein did not predict any of these outcomes in our study.