Galectin-3, Inflammation, and the Risk of Atrial High-Rate Episodes in Patients with Dual Chamber Pacemakers.

Atrial high-rate episodes (AHREs) are atrial tachyarrhythmias that are exclusively detected by cardiac implantable electronic devices (CIEDs) with an atrial lead. The objective of this study was to investigate the incidence and predictive factors for AHREs, and to evaluate the ability of inflammation biomarkers to predict the occurrence of AHREs. 102 patients undergoing CIED procedure who received a dual chamber pacemaker were included. CIED interrogation was performed 1 year after the implantation procedure. Patients were divided into groups according to the occurrence of AHREs, which was the primary endpoint of the study. The mean age of the patients was of 73 ± 8.6 years and 48% were male. The incidence of AHREs was 67% at 1 year follow-up. Patients with AHREs were older, had higher left atrial indexed volume (LAVi), higher baseline galectin-3 levels (1007.5 ± 447.3 vs. 790 ± 411.7 pg/mL) and received betablockers more often, along with amiodarone and anticoagulants. Interestingly, the CHADSVASC score did not differ significantly between the two groups. A cut-off value of galectin > 990 pg/mL predicted AHREs with moderate accuracy (AUC of 0.63, 95% CI 0.52 to 0.73, p = 0.04), and this association was confirmed in the univariate regression analysis (OR 1.0012, 95% CI 1.0001 to 1.0023, p = 0.0328). However, based on the multivariate regression analysis, galectin lost its prognostic significance under the effect of LAVi, which remained the only independent predictor of AHREs (OR 1.0883, 95% CI 1.0351 to 1.1441, p = 0.0009). AHREs are common in CIEDs patients. Galectin-3 may bring additional data in the prediction of AHREs.

Leptin, Galectin-3 and Angiotensin II Type 1 Receptor Polymorphism in Overweight and Obese Patients with Heart Failure - Role and Functional Interplay.

BACKGROUND AND AIMS: Leptin, one of the best-known adipocytes, together with the renin-angiotensin-aldosterone system and galectin-3 are important players in inflammation, arterial hypertension and heart failure pathophysiology. Moreover, uninucleotide A1166C polymorphism is associated with hypertension and poor prognosis in heart failure. The aim of the study was to investigate a possible relationship between leptin serum values, specific heart failure biomarkers and the presence of AT1 receptor A1166C polymorphism in overweight and obese heart failure patients. METHODS: The study included 88 consecutive overweight and obese patients admitted for decompensated heart failure. NT-proBNP, MR-proANP, galectin-3 and leptin levels were determined on the arrival day. Genotyping of the A1166C allele - AT1 receptor gene was performed in all patients in order to find variants. RESULTS: We found a strong positive correlation (r = 0.347, p = 0.001) between leptin serum concentrations and BMI. Leptin levels were not correlated with heart failure biomarkers (NT-proBNP, MR-proANP and galectin-3). All homozygote CC variants were hypertensive, but we registered no significant difference in genetic AC and AA variants distribution between hypertensive and normotensive. Leptin was not significantly modified by the presence of potentially pathogenic A1166C-AT 1 receptor genotypes (AC + CC). But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations. CONCLUSION: Overweight and obese patients with heart failure display high leptin serum levels. Leptin does not offer incremental prognostic value in heart failure overweight and obese patients. But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations, suggesting a worse prognosis probably due to more advanced cardiac fibrosis.

Gender Differences in the Levels of Periodontal Destruction, Behavioral Risk Factors and Systemic Oxidative Stress in Ischemic Stroke Patients: A Cohort Pilot Study.

Background: Due to the higher frequency of ischemic stroke in men compared to women, we aimed to determine if gender differences exist regarding periodontal status and several plasma biomarkers in patients with a recent large artery atherosclerosis ischemic stroke (IS). Material and methods: Patients with their first IS within less than six weeks who were able to undergo periodontal examinations were evaluated. Demographic data, periodontal status, oxidative stress parameters/plasma antioxidant capacity, and C-reactive protein in patients who suffered a recent large artery atherosclerosis ischemic stroke were reccorded. Results: 93 patients were included in the study. More men were smokers (12/57 vs. 3/36) and consumed alcohol (17/57 vs. 3/36), and more women had higher glycemic values (p = 0.023), total cholesterol (p < 0.001), LDL (low-density lipoprotein)-cholesterol (p = 0.010), and HDL (high-density lipoprotein)-cholesterol (p = 0.005) levels. Significantly more men than women had moderate plus severe periodontal disease (p = 0.018), significantly higher levels of nitric oxide (p = 0.034), and significantly lower levels of total antioxidant capacity (p = 0.028). Conclusions: In this pilot study, men seem to be more prone to oxidative stress and to develop more severe forms of periodontitis among patients with stroke, but the results need validation on a larger sample.

Retinal Nerve Fiber Layer Thickness and Oxidative Stress Parameters in Migraine Patients without Aura: A Pilot Study.

BACKGROUND: Migraine is one of the most common disorders and its pathophysiological mechanisms are still under research, oxidative stress being emphasized as an important contributor. This study aimed to analyze the retinal nerve fiber layer (RNFL) thickness and oxidative/anti-oxidant balance in migraine patients. METHODS: Two groups of subjects were evaluated: a group of patients with migraine and a control group of healthy volunteers. RNFL thickness was assessed for all subjects by the ocular coherence tomography spectral domain (OCT-SD). The oxidative stress parameter, namely nitric oxide (NOx), malondialdehyde (MDA), and total oxidative stress (TOS) were assessed. The antioxidant capacity of plasma was evaluated by assessing the level of catalase, and total anti-oxidative (TOS) capacity. Migraine severity was graded using the Migraine Disability Assessment Score (MIDAS) questionnaire. RESULTS: All the oxidative stress parameters (NOx, MDA, and TOS) were significantly increased, and both parameters for anti-oxidative status were significantly decreased in the migraine group compared with the control group (p < 0.0001). Significant correlations with all the quadrants and different oxidative stress parameters were found, most involved being temporal quadrant. A significant positive correlation between catalase and macular RNFL thickness (inner ring, temporal quadrant) in migraine patients, for both eyes, was observed (p = 0.014 for the right eye and p = 0.12 for the left eye). CONCLUSION: The assessment of the oxidative stress/anti-oxidative balance together with RFLN thickness can constitute a promising method to evaluate the progression of the diseases. It can also contribute to the estimation of the efficiency of various therapies targeting oxidative stress and associated inflammation.

Enhancement of bone consolidation using high-frequency pulsed electromagnetic short-waves and titanium implants coated with biomimetic composite embedded into PLA matrix: in vivo evaluation.

PURPOSE: Bone consolidation after severe trauma is the most challenging task in orthopedic surgery. This study aimed to develop biomimetic composite for coating Ti implants. Afterwards, these implants were tested in vivo to assess bone consolidation in the absence or the presence of high-frequency pulsed electromagnetic short-waves (HF-PESW). MATERIALS: Biomimetic coating was successfully developed using multi-substituted hydroxyapatite (ms-HAP) functionalized with collagen (ms-HAP/COL), embedded into poly-lactic acid (PLA) matrix (ms-HAP/COL@PLA), and subsequently covered with self-assembled COL layer (ms-HAP/COL@PLA/COL, named HAPc). METHODS: For in vivo evaluation, 32 Wistar albino rats were used in four groups: control group (CG) with Ti implant; PESW group with Ti implant+HF-PESW; HAPc group with Ti implant coated with HAPc; HAPc+PESW group with Ti implant coated with HAPc+HF-PESW. Left femoral diaphysis was fractured and fixed intramedullary. From the first post-operative day, PESW and HAPc+PESW groups underwent HF-PESW stimulation for 14 consecutive days. Biomimetic coating was characterized by XRD, HR-TEM, SEM, EDX and AFM. RESULTS: Osteogenic markers (ALP and osteocalcin) and micro-computed tomography (CT) analysis (especially bone volume/tissue volume ratio results) indicated at 2 weeks the following group order: HAPc+PESW>HAPc≈PESW (P>0.05) and HAPc+PESW>control (P<0.05), indicating the higher values in HAPc+PESW group compared to CG. The fracture-site bone strength showed, at 2 weeks, the highest average value in HAPc+PESW group. Moreover, histological analysis revealed the most abundant COL fibers assembled in dense bundles in HAPc-PESW group. At 8 weeks, micro-CT indicated higher values only in HAPc+PESW group vs CG (P<0.05), and histological results showed a complete-healed fracture in groups: HAPc+PESW, HAPc and PESW, but with more advanced bone remodeling in HAPc+PESW group. CONCLUSION: Using Ti implants coated by HAPc jointly with HF-PESW stimulation positively influenced the bone consolidation process, especially in its early phase, thus potentially providing a superior strategy for clinical applications.

Enhancement of bone consolidation using high-frequency pulsed electromagnetic fields (HF-PEMFs): An experimental study on rats.

In vitro studies showed that high-frequency pulsed electromagnetic fields (HF-PEMFs) increase the activity/expression of early and late osteogenic markers and enhance bone mineralization. The main aim of this study was to investigate the in vivo effects of HF-PEMFs on fracture healing using a rat model. A femur fracture was established by surgery in 20 male Wistar rats. Titanium nails were implanted to reduce and stabilize the fracture. After surgery, 20 rats were equally divided into untreated control and treated group (from the first postoperative day HF-PEMFs at 400 pulses/sec [pps] were applied for 10 minutes/day, for two weeks). Quantitative and qualitative assessment of bone formation was made at two and eight weeks following surgery and included morphological and histological analysis, serological analysis by ELISA, micro-computed tomography (micro-CT), and three-point bending test. At two weeks in HF-PEMF group, soft callus was at a more advanced fibrocartilaginous stage and the bone volume/total tissue volume (BV/TV) ratio in the callus area was significantly higher compared to control group (p = 0.047). Serum concentration of alkaline phosphatase (ALP) and osteocalcin (OC) was significantly higher in HF-PEMF group (ALP p = 0.026, OC p = 0.006) as well as the mechanical strength of femurs (p = 0.03). At eight weeks, femurs from HF-PEMF group had a completely formed woven bone with dense trabeculae, active bone marrow, and had a significantly higher BV/TV ratio compared to control (p = 0.01). HF-PEMFs applied from the first postoperative day, 10 minutes/day for two weeks, enhance bone consolidation in rats, especially in the early phase of fracture healing.

Musculoskeletal ultrasound guided manoeuvres - a security profile.

BACKGROUND: In daily rheumatology clinical practice, routine interventional musculoskeletal ultrasound (MSUS) guided maneuvers such as aspiration, intraarticular or periarticular drug injections require efficient cleaning and disinfection methods for both transducer and patient's skin. AIM: To study the efficacy of probe and skin disinfection measures after using simple protocols, to identify the prevalence of septic and other drug related side effects after MSUS guided interventions and to quantify the total procedure time. MATERIAL AND METHODS: Recruitment of consecutive patients with different joint/ periarticular MSUS guided interventions was made in 3 medical centers. Bacterial load was determined on the transducers footprint after dry cleaning with the removal of any gel trace and on patients' skin after rigorous skin disinfection with either Bethadine or alcohol 70° and Bethadine. Non-sterile gel was used as an ultrasound transmission medium. The time spent for some of the invasive procedures was quantified. RESULTS: Nine hundred and ninety eight MSUS guided interventional maneuvers were performed in 945 patients with inflammatory and degenerative musculoskeletal pathologies. Staphylococcus epidermidis was identified in 13.33% cases of the skin bacterial load analysis and in 37.50% cases of the footprint analysis. In two patients pathogenetic germs were detected on the skin. No septic post-procedural complications were reported. In 0.6% of the cohort other side effects occurred: aseptic osteonecrosis, skin depigmentation at injection site and iatrogenic microcristaline reactions. The median time frame dedicated to the intervention was 6 minutes. CONCLUSION: Rigorous transducer dry cleaning and Bethadine / Bethadine and alcohol 70° skin disinfection are efficacious methods. The risk for septic complications and other drug related side effects related to MSUS guided injections is very low in this context. A correct injection technique must accompany the previous requests. Rapid and safe interventional maneuvers reduce the risks and control the costs of the healthcare system.

The response of circulating leptin levels to exercise stress testing in subjects diagnosed with metabolic syndrome.

Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of 55 ± 7 years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1-10 patients with a true positive test, group 2-18 patients with a true negative test, and group 3-39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS (9.42 ± 11.08 ng/mL before and 8.18 ± 11.5 ng/mL after the exercise stress test, P = 0.0005, r = 0.874). In groups 1 (8.98 ± 9.09 at rest versus 5.98 ± 8.73 ng/mL after the exercise test, P = 0.002) and 3 (8.6 ± 10.53 at rest versus 6.91 ± 9.07 ng/mL, P = 0.0005), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort (9.49 ± 11.36 ng/ml) and after (9.46 ± 13.81 ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values.

NT-pro-BNP during isotonic and isometric exercise in heart failure patients with preserved LV ejection fraction.

BACKGROUND: NT-pro-BNP level is increased in both systolic and diastolic heart failure (HF) and furthermore increases more during exercise. In diastolic HF, NT-pro-BNP might increase more during isometric exercise than during isotonic exercises because of increased afterload. We studied NT-pro-BNP values during isometric (hand-grip) and isotonic (cycloergometer) exercise in HF patients with preserved left ventricular ejection fraction and different degrees of diastolic dysfunction. METHODS: We studied 87 patients, aged 58 ± 7.9 years, 42.6% females, with heart failure with LVEF > 40% and diastolic dysfunction. The patients were randomly distributed in two groups: 43 patients (Group I) and 44 patients (Group II). Group I underwent ramp exercise testing on a cycloergometer. Group II performed an isometric handgrip test. Plasma NT-pro-BNP levels were measured at rest and immediately after exercise. RESULTS: An abnormal relaxation (AR) pattern was recorded in 30 patients of Group I and 31 patients of Group II. Pseudonormalisation (PSN) and restrictive (R) pattern were noted in 13 patients of each group. As concerns Group I, NT-pro-BNP levels were increased in all patients, particularly in those with PSN or R pattern (p < 0.05). During exercise NT-pro-BNP decreases significantly in AR (1033 ± 516.63 to 800.51 ± 675.89 pg/mL) but not in PSN or R patients (1656.75 ± 977.48 to 1486.38 ± 1182.51 pg/mL). For Group II, NT-pro-BNP registered a similar increase as in Group I, with maximal values in PSN or R subgroup as compared to abnormal relaxation (p < 0.05). At peak exercise, NT-pro-BNP was practically unchanged as compared to the rest values for the whole group (-6%) and for the two subgroups (AR -6.7% and PSN or R -5.21%). We compared rest and exercise NT-pro-BNP with E/E' ratio > 12 in order to identify increased diastolic filling pressure in the LV; AUC was 0.70 and 0.66 for rest and exercise NT-pro-BNP in case of isotonic testing and 0.74 and 0.72 in case of isometric exercise. CONCLUSIONS: Our data suggest that in HF patients with preserved left ventricular ejection fraction, moderate isotonic and isometric exercises do not determine a significant increase (isometric exercise) or even decrease (isotonic exercise) in the value of NT-pro-BNP.

Plasma nitric oxide metabolite levels increase during successive exercise stress testing - A link to delayed ischemic preconditioning?

BACKGROUND: Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning. OBJECTIVES: To determine whether plasma nitrates and nitrites (NO(x) (-), as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement METHODS: Twenty-two patients with ischemic heart disease each performed two effort tests at 24-h intervals. Plasma NO(x) (-) level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical endpoints and were compared between the two tests. RESULTS: Plasma NO(x) (-)increased slightly after the first exercise test compared with pretest value (17.05+/-1.6 mumol/mL versus 15.38+/-1.4 mumol/mL). In turn, after the second test there was a significant rise in NO(x) (-) level (23.65+/-2.2 mumol/mL versus 15.10+/-1.3 mumol/mL, P<0.03). The pretest values were almost identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although ischemic stress was the same, ST depression was significantly lower (P<0.01) for the second test (0.85+/-0.06 mm versus 1.73+/-0.16 mm). CONCLUSION: Our study shows an increased plasma NO(x) (-)level after the second of two consecutive exercise stress tests at 24-h intervals, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as a trigger and effector of ischemic preconditioning.