Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model.

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood-brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic-pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic-pituitary unit, although its effect appears to be partially dependent on the animal's immune status.

Oral anticoagulation therapy in atrial fibrillation patients at high risk of bleeding: Clinical characteristics and treatment strategies based on data from the Polish multicenter register of atrial fibrillation (POL-AF).

BACKGROUND: Despite its benefits, oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF) is associated with hemorrhagic complications. AIMS: We aimed to evaluate clinical characteristics of AF patients at high risk of bleeding and the frequency of OAC use as well as identify factors that predict nonuse of OACs in these patients. METHODS: Consecutive AF patients hospitalized for urgent or planned reasons in cardiac centers were prospectively included in the registry in 2019. Patients with HAS-BLED ≥3 (high HAS-BLED group) were assumed to have a high risk of bleeding. RESULTS: Among 3598 patients enrolled in the study, 29.2% were at high risk of bleeding (44.7% female; median [Q1-Q3] age 72 [65-81], CHA2DS2-VASc score 5 [4-6], HAS-BLED 3 [3-4]). In this group, 14.5% of patients did not receive OACs, 68% received NOACs, and 17.5% VKAs. In multivariable analysis, the independent predictors of nonuse of oral OACs were as follows: creatinine level (odds ratio [OR], 1.441; 95% confidence interval [CI], 1.174-1.768; P <0.001), a history of gastrointestinal bleeding (OR, 2.918; 95% CI, 1.395-6.103; P = 0.004), malignant neoplasm (OR, 3.127; 95% CI, 1.332-7.343; P = 0.009), and a history of strokes or transient ischemic attacks (OR, 0.327; 95% CI, 0.166-0.642; P = 0.001). CONCLUSIONS: OACs were used much less frequently in the group with a high HAS-BLED score than in the group with a low score. Independent predictors of nonuse of OACs were creatinine levels, a history of gastrointestinal bleeding, and malignant neoplasms. A history of stroke or transient ischemic attack increased the chances of receiving therapy.

The Effects of Seven-Day Exposure to Silver Nanoparticles on Fertility and Homeostasis of Zebrafish (Danio rerio).

Silver nanoparticles (AgNPs) are found in open waters, but the effect of their low concentrations on an organism's homeostasis is not fully understood. The aim of the study was to determine the short-term exposure effects of AgNPs coated by PvP (polyvinylpyrrolidone) on the homeostasis of livers and gonads in zebrafish. Sexually mature zebrafish were exposed for seven days to silver ions (0.01 mg/dm3) or AgNPs (0.01; 0.05; 0.1; 0.5; 1.0 mg/dm3). On the last day, the liver, testes, and ovaries were subjected to a histology analysis. In the liver, we analyzed the expression of the cat, gpx1a, gsr, sod1, and cyp1a genes. On the last day of the experiment, the lowest survival rate was found in the AgNPs 0.05 mg/dm3 group. The histological analysis showed that AgNPs and silver ions cause an increase in the area of hepatocytes. The highest proliferation index of hepatocytes was found in the AgNP 0.05 mg/dm3 group. Furthermore, AgNPs were found to interfere with spermatogenesis and oogonesis as well as reduce the expression levels of the cat, gpx1a, and sod1 genes in the liver compared with the control group. Based on the results, it can be concluded that exposure to AgNPs causes cytotoxic changes in zebrafish, activates the immune system, negatively affects the process of meiosis in the gonads, and generates oxidative stress.

Acute Effect of Caffeine on the Synthesis of Pro-Inflammatory Cytokines in the Hypothalamus and Choroid Plexus during Endotoxin-Induced Inflammation in a Female Sheep Model.

This study was designed to determine the effect of acute caffeine (CAF) administration, which exerts a broad spectrum of anti-inflammatory activity, on the synthesis of pro-inflammatory cytokines and their receptors in the hypothalamus and choroid plexus (ChP) during acute inflammation caused by the injection of bacterial endotoxin-lipopolysaccharide (LPS). The experiment was performed on 24 female sheep randomly divided into four groups: control; LPS treated (iv.; 400 ng/kg of body mass (bm.)); CAF treated (iv.; 30 mg/kg of bm.); and LPS and CAF treated. The animals were euthanized 3 h after the treatment. It was found that acute administration of CAF suppressed the synthesis of interleukin (IL-1ß) and tumor necrosis factor (TNF)α, but did not influence IL-6, in the hypothalamus during LPS-induced inflammation. The injection of CAF reduced the LPS-induced expression of TNF mRNA in the ChP. CAF lowered the gene expression of IL-6 cytokine family signal transducer (IL6ST) and TNF receptor superfamily member 1A (TNFRSF1) in the hypothalamus and IL-1 type II receptor (IL1R2) in the ChP. Our study on the sheep model suggests that CAF may attenuate the inflammatory response at the hypothalamic level and partly influence the inflammatory signal generated by the ChP cells. This suggests the potential of CAF to suppress neuroinflammatory processes induced by peripheral immune/inflammatory challenges.

Why Did All Patients with Atrial Fibrillation and High Risk of Stroke Not Receive Oral Anticoagulants? Results of the Polish Atrial Fibrillation (POL-AF) Registry.

BACKGROUND: Most atrial fibrillation (AF) patients are at high risk of thromboembolic, and the use of oral anticoagulants (OACs) is advised in such cases. The aim of the study was to evaluate the frequency at which OACs were used in patients with AF and high risk thromboembolic complications, and identify factors that result in OACs not being used in the researched group of patients. METHODS: The prospective, multicenter and non-interventional POL-AF registry is a study that includes AF patients from ten Polish cardiology centers. They were consecutively hospitalized between January and December of 2019. All the patients in the study were of high stroke risk. RESULTS: A total of 3614 patients with AF and high stroke risk were included. Among the total study population, 91.5% received OAC therapy; antiplatelet therapy was prescribed for 3.7% of patients, heparin for 2.7%, and 2.1% of patients did not receive any stroke prevention therapy. Independent predictors of no OAC prescription were intracranial bleeding (OR 0.15, 95%CI 0.07-0.35, p < 0.001), gastrointestinal bleeding (OR 0.25, 95%CI 0.17-0.37, p < 0.001), cancer (OR 0.37, 95%CI 0.25-0.55, p < 0.001), hospitalization due to acute coronary syndrome (OR 0.48, 95%CI 0.33-0.69, p < 0.001), and anemia (OR 0.62, 95%CI 0.48-0.81, p < 0.001). CONCLUSIONS: Most AF patients with a high thromboembolic risk received OACs. The factors predisposing a lack of OAC use in these patients were conditions that significantly increased the risk of bleeding complications.

The Role of Transcription Factors in Gonad Development and Sex Differentiation of a Teleost Model Fish-Guppy (Poecilia reticulata).

The guppy (Poecilia reticulata) is one of the world's most popular ornamental fish. Due to lecithotrophic viviparous, it is commonly used in toxicological studies and environmental monitoring. This study aimed to investigate the molecular mechanisms of gonad development and differentiation during guppy ontogenesis. The study mainly focused on the role and localization of potential specific sex markers and transcription factors: Sox9, Dmrt1, Erß. For histological analysis, guppies of both sexes were collected at 1, 60, and 360 dph (day post-hatching). The gonads morphology and immunohistochemistry detection of mentioned markers localization were performed. The expression of Sox9 protein was compared between sexes. Histological analysis revelated all types of male germinal cells in 60 dph guppy's testes. Maturated oocytes were visible in the ovaries of 360 dph fish. The Sox9 expression varied in spermatocytes and spermatids, from cellular to nuclear localization, and was higher in ovaries. Dmrt1 was detected in all testes groups and 360 dph ovaries. The Erß was observed in both sexes at 60 and 360 dph. For the first time, the localization of transcription factors in guppy during ontogenesis was traced. The Sox9 designation as a factor regulating the development of germinal cells in adult guppies may facilitate the analysis of xenobiotics' influence on fish's reproductive system.

Effect of Acute and Prolonged Inflammation on the Gene Expression of Proinflammatory Cytokines and Their Receptors in the Anterior Pituitary Gland of Ewes.

An acute and prolonged inflammation inhibits the reproduction process by the disruption of the neurohormonal activity of the hypothalamic-pituitary-gonadal axis. It is thought that these changes may be caused by proinflammatory cytokines, i.e., interleukin (IL) -1ß, IL-6 and tumor necrosis factor (TNF) α. The aim of this study was to determine the effect of an acute and prolonged inflammation on the expression of genes encoding cytokine and their receptors, gonadotropin releasing hormone receptor (GnRHR), beta subunits of luteinizing hormone (LHß) and follicle-stimulating (FSHß) in the anterior pituitary (AP). Moreover, the circulating concentration of LH and FSH was also assayed. Two experiments were carried out on adult ewes which were divided into two control groups and treated with lipopolysaccharide (LPS; 400 ng / kg). Acute inflammation was caused by a single injection of LPS into the external jugular vein, while the chronic inflammation was induced by seven times LPS injection (one a day). In both experiments, animals were euthanized 3h after the last LPS / NaCl injection and the blood samples collected 15 min before euthanasia. An acute inflammation stimulates the expression of the IL-1ß, IL-6 and TNFα genes and their receptors in the AP of sheep. Prolonged inflammation increased TNFα gene expression and both types of TNFα and IL-6 receptors. Both an acute and prolonged inflammation inhibited LHß gene expression in the AP and reduced LH level in blood. A sevenfold LPS injection raises FSH concentration. The gene expression of GnRHR was reduced in the ovine AP only after a single injection of endotoxin. Our results suggest that there are important differences in the way how an acute and prolonged inflammation influence proinflammatory cytokines and their receptors gene expression in the AP of anestrous ewes, which could be reflected by differences in the AP secretory activity during these states.

The Impact of Photoperiod on the Leptin Sensitivity and Course of Inflammation in the Anterior Pituitary.

Leptin has a modulatory impact on the course of inflammation, affecting the expression of proinflammatory cytokines and their receptors. Pathophysiological leptin resistance identified in humans occurs typically in sheep during the long-day photoperiod. This study aimed to determine the effect of the photoperiod with relation to the leptin-modulating action on the expression of the proinflammatory cytokines and their receptors in the anterior pituitary under physiological or acute inflammation. Two in vivo experiments were conducted on 24 blackface sheep per experiment in different photoperiods. The real-time PCR analysis for the expression of the genes IL1B, IL1R1, IL1R2, IL6, IL6R, IL6ST, TNF, TNFR1, and TNFR2 was performed. Expression of all examined genes, except IL1ß and IL1R2, was higher during short days. The leptin injection increased the expression of all examined genes during short days. In short days the synergistic effect of lipopolysaccharide and leptin increased the expression of IL1B, IL1R1, IL1R2, IL6, TNF, and TNFR2, and decreased expression of IL6ST. This mechanism was inhibited during long days for the expression of IL1R1, IL6, IL6ST, and TNFR1. The obtained results suggest the occurrence of leptin resistance during long days and suggest that leptin modulates the course of inflammation in a photoperiod-dependent manner in the anterior pituitary.

Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation.

The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin-lipopolysaccharide (LPS; 400 ng/kg)-attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed (p < 0.05) LPS-stimulated synthesis of cytokines such as interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor (TNF) α in the POA, and this effect was similar to that induced by the treatment with systemic AChE inhibitor-donepezil (2.5 mg/animal). On the other hand, both AChE inhibitors did not influence the gene expression of these cytokines and their corresponding receptors in the CP. It was found that this structure seems to not express the neuronal acetylcholine (ACh) receptor subunit alpha-7, required for anti-inflammatory action of ACh. The mechanism of action involves inhibition of the proinflammatory cytokine synthesis on the periphery as well as inhibition of their de novo synthesis rather in brain microvessels and not in the CP. In conclusion, it is suggested that the AChE inhibitors incapable of reaching brain parenchyma might be used in the treatment of neuroinflammatory processes induced by peripheral inflammation.

Review: Apelin in disease.

Apelin, a regulatory peptide, is a ligand of the APJ receptor that belongs to the G protein-coupled receptor family. Apelin and APJ are widely distributed in the body and play potential physiological roles in the cytoprotection of many internal organs. This review article summarizes information about the roles of the apelin/APJ system in neurological, metabolic, hypertension, respiratory, gastrointestinal, hepatic, kidney and cancerous diseases. It is suggested that apelin positively affects the treatment of non-cancerous diseases and may be considered as a therapeutic drug in many illnesses. However, in cancers, apelin appears as a tumour growth stimulator, and its suggested role is as a marker in the diagnosis of tumour cancers in tissues. In summary, apelin has certain therapeutic abilities and can be useful in the treatment of, e.g., insulin resistance, hypertension, etc., but it also can sometimes serve as a negative factor.

A study to evaluate the prevalence and determinants of stress coping strategies in heart failure patients in Poland (CAPS-LOCK-HF sub-study).

BACKGROUND AND AIM: We aimed to evaluate the prevalence and determinants of different stress coping strategies in Polish patients suffering from heart failure with reduced ejection fraction (HFREF). METHODS: This manuscript is a sub-study of the CAPS-LOCK-HF multicentre psychological status assessment of patients with HFREF. Patients with > six-month history of HFREF and clinical stability for ≥ three months and left ventricular ejection fraction (LVEF) < 45% were enrolled in the study. Demographic and clinical variables were obtained from medical records, while a standardised Coping Inventory for Stressful Situations (CISS) was applied to all subjects. RESULTS: The study comprised 758 patients (599 men; 79%) with a median age of 64 years (IQR 58-71). Median LVEF was 33% (25-40). Subjects most commonly used task-oriented coping strategies (median CISS score 55 points; IQR 49-61), followed by avoidance (45 points; 39-50) and emotion-oriented coping strategies (41 points; 34-48). Distraction-based avoidance coping strategies (20 points; 16-23) were more pronounced than social diversion strategies (16 points; 14-19). Multiple regression analysis showed that higher New York Heart Association (NYHA) class and lower systolic blood pressure were independent predictors of task-oriented style. Emotion-oriented coping was more common among females and higher NYHA classes, and in patients who did not take angiotensin-converting enzyme inhibitors. Patients who used avoidance-oriented strategies were more frequently those in sinus rhythm on assessment and those who had less history of neoplastic disease. CONCLUSIONS: Patients with HFREF most commonly use favourable task-oriented coping strategies. However, female patients and those with higher NYHA classes tend to use potentially detrimental emotion-oriented coping strategies.

The Impact of Left Atrial Surface Area and the Second Generation Cryoballoon on Clinical Outcome of Atrial Fibrillation Cryoablation.

AIMS: In this observational study, we examine the significance of the left atrial (LA) surface area and compare the clinical usage of the Arctic Front Advance (CBA) versus Arctic Front (CB) cryoballoon with the intent to investigate the impact of each in terms of long-term freedom from atrial fibrillation (AF) for patients with nonvalvular AF. METHODS: Pulmonary vein isolation (PVI) was performed while using a cryoballoon ablation catheter in conjunction with an intraluminal circular diagnostic mapping catheter, Achieve. The consecutive patients ablated with CBA were matched with patients previously ablated with CB, using propensity score matching. The primary endpoint of this observational single-center retrospective study was the first observation of electrocardiogram-documented recurrence of atrial arrhythmias lasting >30 seconds. RESULTS: The patient demographic data were similar in the CBA- and CB-group (N = 188 patients each group). In all patients in the CBA-group and in 95% of the patients in the CB group, acute procedural PVI of all veins was achieved with the single usage of a 28-mm cryoballoon. The one-year freedom from atrial arrhythmias was significantly better in the CBA- versus the CB-group of patients, 90% versus 64%, respectively. During 15-month clinical follow-up in CBA group, patients with LA area above 23 cm(2) were more likely to experience recurrence of AF (23%) than patients with LA area below 23 cm(2) (7%). CONCLUSIONS: Comparing one-year outcomes, the CBA is superior to the CB with regards to maintenance of normal sinus rhythm. When using the CBA catheter, an enlarged LA is associated with a higher recurrence of arrhythmia.

Cryoballoon ablation of atrial fibrillation: How important is the proper selection of patients?

BACKGROUND: Relation between pre-procedural selection of patients and the success rate after a single cryoballoon ablation (CAB) procedure is unknown. METHODS: CAB was performed in 378 (65% male, median age 58 years, 85% paroxysmal atrial fibrillation [AF]) consecutive patients with symptomatic and drug refractory AF. The combined ALARMEc (Atrial fibrillation type, Left Atrium size, Renal insufficiency, Metabolic syndrome, cardiomyopathy) risk score was calculated for each individual patient. The end-point of the study was the first AF, atrial flutter or atrial tachycardia recurrence after the 3-month blanking period in the 1-year follow-up since the index procedure, in the absence of anti-arrhythmic (class I and III) therapy. RESULTS: Single and multi-catheter approach was used in 79% and 21% of patients, respectively. The acute success rate with single and multi-catheter approach was 79% and 99%, respectively. The overall 1-year success rate after a single CAB procedure was 70%. The 1-year outcome was: 83%, 70%, 60%, 40% and 29% in patients with ALARMEc risk score: 0, 1, 2, 3 and 5, respectively. Total rate of complications was 11%, including transient phrenic nerve palsy in 9.5% of cases. CONCLUSIONS: Multi-catheter approach was needed in 21% of patients to achieve acute pulmonary vein isolation. Patients with low (≤ 1) ALARMEc risk score, preferably young individuals with sole paroxysmal AF (ALARMEc = 0), are best candidates for CBA procedure. Performing CBA in patients with higher (> 2) ALARMEc risk score should be avoided. Phrenic nerve palsy was a transient complication.

Cryoballoon ablation in young patients with lone paroxysmal atrial fibrillation.

INTRODUCTION AND OBJECTIVES: Long-term efficacy following cryoballoon ablation of lone paroxysmal atrial fibrillation remains unknown. We describe long-term follow-up results of the single cryoballoon ablation procedure. METHODS: Pulmonary vein isolation was performed in 103 patients (72 male; median age 52 years) with symptomatic lone paroxysmal atrial fibrillation. The end-point of this observational cohort study was first electrocardiogram-documented recurrence of arrhythmia (atrial fibrillation, atrial tachycardia, or atrial flutter) during the 5-year follow-up, in the absence of anti-arrhythmic treatment. RESULTS: Acute complete pulmonary vein isolation was achieved in 86% of the patients with a single cryoballoon. The 6-month, 1-year, and 5-year success rate after a single procedure was 94%, 91%, and 77%, respectively. Arrhythmia recurrence was observed in 24 cases at a median of 14.8 months [range, 8.0-16.8 months]. Thirteen symptomatic patients were well controlled on beta-blockers only. Seven symptomatic patients had anti-arrhythmic treatment (class IC in 5 patients; dronedarone in 2 patients) introduced during the blanking period. Two of them had early arrhythmia recurrence within the blanking period only; they were arrhythmia-free in further follow-up on dronedarone. The rate of complications was relatively low and included a 4.8% incidence of transient phrenic nerve palsy. CONCLUSIONS: A single cryoballoon ablation procedure for lone paroxysmal atrial fibrillation resulted in high rates of acute, medium-term, and long-term efficacy. The rate of complications is relatively low and includes a 4.8% incidence of transient phrenic nerve palsy.

Learning curve in cryoballoon ablation of atrial fibrillation: eight-year experience.

BACKGROUND: We analyzed the procedural experience cryoballoon ablation (CBA) of atrial fibrillation (AF) gained over 8 years in a high-volume centre to understand the influence of the learning curve on feasibility, safety and clinical outcome. METHODS AND RESULTS: In 424 patients (62% male) with drug-refractory AF, CBA was performed between 2005 and 2012. The analyzed period was divided into 8 calendar years. The endpoint of the study was arrhythmia recurrence after the 3-month blanking period in the 1-year follow-up since the index procedure, in the absence of anti-arrhythmic drugs class I and III. A combined AF type, Left Atrium size, Renal insufficiency, MEtabolic syndrome, cardiomyopathy (ALARMEc) risk score was calculated for each patient. The overall 1-year success rate of a single CBA was 73%. Continuous increase in 1-year success rate was observed with successive years of the study. The gradual improvement in outcome was related to gradual fall in ALARMEc risk score in successive patients. A continuous decrease in fluoroscopy and procedure time was observed in each subsequent year. CONCLUSIONS: CBA, followed by the proper selection of patients, facilitates a satisfactory outcome, especially in patients at an early stage of PV-trigger-dependent AF. Still, as with each new technology, it requires completion of a learning curve.

Score associated with the outcome after multiple ablation procedures in patients with atrial fibrillation.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is now established therapeutic option. Multiple procedures (MPs) are often needed to achieve the satisfactory outcome. The aim of the study was to assess the outcome after MPs in AF patients categorized to risk-score groups. METHODS: We followed a cohort of consecutive 911 (69% male; median 59 years) patients with AF (58% paroxysmal) who had CAAF performed. ALARMEC (Atrial fibrillation type, Left Atrium size, Renal insufficiency, MEtabolic syndrome, cardiomyopathy) risk score was calculated for each patient. The end point was maintenance of sinus rhythm at the follow-up of 60 months. RESULTS: We performed 1,199 CAAF procedures. One, two, and three procedures were performed in 663 (73%), 208 (23%), and 40 (4%) patients, respectively. Outcome after the first procedure (56%) was improved with MPs (76%). MPs > 2 were performed in 1%, 3%, 5%, 6%, and 10% patients with ALARMEC score of 0, 1, 2, 3, and 4, respectively. MPs were successful in 89%, 86%, 81%, 65%, and 43% of patients with ALARMEC score of 0, 1, 2, 3, and 4, respectively. Outcome in 174 (19%) patients on antiarrhythmic drugs (AADs) was 85%, 68%, 75%, 44%, and 39% in ALARMEC score: 0, 1, 2, 3, and 4, respectively. Outcome in 737 (81%) patients without AAD was 90%, 85%, 80%, 77%, and 69% in ALARMEC score of 0, 1, 2, 3, and 4, respectively. CONCLUSION: The moderate success rate after index procedure of CAAF can be further improved with multiple ones and AAD.

Synthesis, quality control and determination of metallic impurities in 18F-fludeoxyglucose production process.

AIM: The aim of this study was to synthesize 18FDG in some consecutive runs and check the quality of manufactured radiopharmaceuticals and to determine the distribution of metallic impurities in the synthesis process. BACKGROUND: For radiopharmaceuticals the general requirements are listed in European Pharmacopeia and these parameters have to be checked before application for human use. MATERIALS AND METHODS: Standard methods for the determination of basic characteristics of radiopharmaceuticals were used. Additionally, high resolution γ spectrometry was used for the assessment of nuclidic purity and inductively coupled plasma with mass spectrometry to evaluate metallic content. RESULTS: Results showed sources and distribution of metallic and radiometallic impurities in the production process. Main part is trapped in the initial separation column of the synthesis unit and is not distributed to the final product in significant amounts. CONCLUSIONS: Produced 18FDG filled requirements of Ph.Eur. and the content of radionuclidic and metallic impurities was in the acceptable range.

Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success.

AIMS: Long-term efficacy following cryoballoon (CB) ablation of atrial fibrillation (AF) remains unknown. This study describes 5 years follow-up results and predictors of success of CB ablation in patients with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: In total, 163 patients were enrolled with symptomatic, drug refractory PAF. Pulmonary vein isolation (PVI) with CB technique was performed. Primary endpoint of this consecutive single-centre study was first electrocardiogram-documented recurrence of AF, atrial tachycardia or atrial flutter (AFLAT). Five years success rate after single CB ablation was 53%. In 70% of the patients acute complete PVI was achieved with a single 28 mm balloon. The univariate predictors of AFLAT recurrence were (1) size of left atrium, with normalized left atrium (NLA) ≥10.25 [hazard ratios (HR) of 1.81, 95% confidence interval (CI): 1.28-2.56] when compared with NLA <10.25 (35% vs. 53%, P = 0.0001) and (2) renal function, with impaired glomerular filtration rate (GFR) <80 ml/min (HR of 1.26, 95% CI: 1.02-1.57) when compared with GFR ≥80 ml/min (45% vs. 53%, P = 0.041). Normalized left atrium ≥10.25 was the sole independent predictor for outcome (HR 2.11; 95% CI: 1.34-3.31; P = 0.0001). CONCLUSIONS: Sinus rhythm can be maintained in a substantial proportion of patients with PAF even 5 years after circumferential PVI using CB ablation. The rate of decline in freedom from AFLAT was highest within the first 12 months after the index procedure. The patients with enlarged left atrium and/or impaired renal function have lower outcome.