Risk factors for late reconnections after circumferential pulmonary vein isolation guided by lesion size index - Data from repeat invasive electrophysiology procedure.

Background: Late reconnections (LR) of pulmonary veins (PVs) after wide antral circumferential ablation (WACA) using point-to-point radiofrequency (RF) ablation are common. Lesion size index (LSI) is a novel marker of lesion quality proposed by Ensite Precision mapping system, expected to improve PV isolation durability. This study aimed to assess the durability of LSI-guided PVI and the risk factors for LR of PVs. Methods: The prospective study included 33 patients with paroxysmal atrial fibrillation (PAF) who underwent (1) the index LSI-guided WACA procedure (with target LSI of 5.5-6.0 for anterior and 5.0-5.5 for posterior WACA segments) and (2) the 3-month protocol-mandated re-mapping procedure in all patients, irrespective of AF recurrence after the index procedure. Ablation parameters reported by Ensite mapping system were collected retrospectively. The inter-lesion distance (ILD) between all adjacent WACA lesions was calculated off-line. Association between index ablation parameters and the LRs of PVs at 3 months was analyzed. Results: The median patient age was 61 (IQR: 53-64) years and 55% of them were males. At index procedure, the first-pass WACA isolation rate was higher for the left PVs than the right PVs (64 vs. 33%, p = 0.014). In addition, a low acute reconnection rates were observed, as follows: in 12.1% of patients, in 6.1% of WACA circles, in 3.8% of WACA segments and in 4.5% of PVs. However, the 3-month remapping study revealed LR of PV in 63.6% of patients, 37.9% of WACA circles, 20.5% of WACA segments and 26.5% of PVs. The LRs were identified mostly along the left anterior WACA segment. Independent risk factors for the LR of WACA were left-sided WACA location (OR 3.216 [95%CI: 1.065-9.716], p = 0.038) and longer ILD (OR 1.256 [95%CI: 1.035-1.523] for each 1-mm increase, p = 0.021). The ILD of > 8.0 mm showed a predictive value for the LR of WACA, with the sensitivity of 84% and specificity of 46%. A single case of cardiac tamponade occurred following the re-mapping invasive procedure. No other complications were encountered. Conclusion: Although the LSI-guided PVI ensures a consistent PVI during the index procedure, LRs of PVs are still common. Besides the LSI, the PVI durability requires an optimal ILD between adjacent lesions, especially along the anterior lateral ridge.

Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists.

Hydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids' non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5-1.9 Å) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid-base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a ß-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.

Micra™ Leadless Intracardiac Pacemaker Implantation: A Safer Option During the Coronavirus Disease 2019 Pandemic.

The Micra™ Transcatheter Pacing System (Medtronic, Minneapolis, MN, USA) is a fairly novel leadless intracardiac pacemaker implanted in the right ventricle via a femoral-vein transcatheter approach. Due to the less-invasive nature of the implantation procedure and its smaller size, patients receiving the Micra™ device tend to experience fewer complications, hospitalizations, and revisions when compared with those with transvenous pacemakers. Certain arrhythmias and conduction abnormalities, such as high-degree atrioventricular blocks, require urgent and timely pacemaker insertion-a necessity that has persisted even during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present a case series of 10 patients with various conduction disease abnormalities who required right ventricle pacemaker implantation during the months of March to May 2020, which was the initial peak of the COVID-19 pandemic in New Jersey, including the enhanced precautions taken to avoid viral spread.

Varietal Differences of Prokupac, Evita and Cokot Zemun Based on Their Anthocyanins Content in Grape Skin Extract.

In this study, we have analyzed the anthocyanin composition of skin extracts of three red grape varieties Prokupac, Evita and Cokot Zemun in order to distinguish these cultivars based on their anthocyanin profile. Also, mechanical analysis of grape bunches and berries was performed. According to our results, seventeen anthocyanins were identified using LC/MS technique and quantitative differences were recorded using HPLC-DAD method. The highest content of total anthocyanins was obtained for Evita variety and the lowest one was recorded in Prokupac. Also, clear differences were observed in anthocyanins ratios. In comparison to Prokupac and Evita varieties, Cokot Zemun was characterized with a high content of coumaroyl derivatives of anthocyanin compounds, while high levels of acetylated derivatives were recorded in Prokupac. Data reported in this study represent a certain contribution to a database of mechanical properties and chemical composition of grape varieties originating from Balkan.

Improvement of Maximal Exercise Performance After Catheter-Ablation of Atrial Fibrillation and Its Prognostic Significance for Long-Term Rhythm Outcome.

Background Rhythm control may improve functional capacity in patients with atrial fibrillation (AF). Long-term exercise tolerance improvement and its prognostic implications following catheter-ablation (CA) of paroxysmal and nonparoxysmal AF are underreported. Methods and Results Consecutive patients underwent cardiopulmonary exercise testing just before and 12 months after their index CA of AF. Follow-up 24-hour Holter recordings were obtained at 6-month intervals post-CA, and any atrial arrhythmia >30 seconds detected after 3 months postprocedure was considered AF recurrence. Of 110 patients (mean age 57.5±10.6 years, 77.2% males) with paroxysmal AF (n=66) or nonparoxysmal AF (n=44), the 12-month exercise tolerance improved significantly in those who maintained sinus rhythm during the first 12 months post-CA (n=96), but not in patients with AF recurrence (n=14). After CA, the 12-month respiratory exchange ratio at maximal workload significantly increased in patients with paroxysmal AF, whereas those with nonparoxysmal AF significantly reduced their heart rate during the 12-month cardiopulmonary exercise testing (all P≤0.001). During the follow-up of 42.8±7.8 months, a total of 29 patients (26.3%) experienced recurrent AF. On multivariate analysis including patients without recurrent AF at 12 months after CA, the extent of work time improvement at follow-up cardiopulmonary exercise testing was independently associated with the rhythm outcome beyond 12 months postprocedure (hazard ratio of 0.936 [95% CI, 0.894-0.979] for each 10 seconds increase in the work time following ablation, P=0.004). Conclusions CA of AF was associated with recovery of exercise intolerance in patients with paroxysmal AF or nonparoxysmal AF. Inability to improve exercise capacity at 12 months post-CA was an independent risk factor for later AF recurrence.

Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes.

Increased pollution by plastics has become a serious global environmental problem, but the concerns for human health have been raised after reported presence of microplastics (MPs) and nanoplastics (NPs) in food and beverages. Unfortunately, few studies have investigate the potentially harmful effects of MPs/NPs on early human development and human health. Therefore, we used a new platform to study possible effects of polystyrene NPs (PSNPs) on the transcription profile of preimplantation human embryos and human induced pluripotent stem cells (hiPSCs). Two pluripotency genes, LEFTY1 and LEFTY2, which encode secreted ligands of the transforming growth factor-beta, were downregulated, while CA4 and OCLM, which are related to eye development, were upregulated in both samples. The gene set enrichment analysis showed that the development of atrioventricular heart valves and the dysfunction of cellular components, including extracellular matrix, were significantly affected after exposure of hiPSCs to PSNPs. Finally, using the HiPathia method, which uncovers disease mechanisms and predicts clinical outcomes, we determined the APOC3 circuit, which is responsible for increased risk for ischemic cardiovascular disease. These results clearly demonstrate that better understanding of NPs bioactivities and its implications for human health is of extreme importance. Thus, the presented platform opens further aspects to study interactions between different environmental and intracellular pollutions with the aim to decipher the mechanism and origin of human diseases.

Severe Anaphylactic Reaction to Diclofenac during Intravenous Anesthesia for In Vitro Fertilization.

We present a case of a severe anaphylactic reaction to diclofenac, administered as an intravenous infusion in a 45-year-old patient, during intravenous anesthesia for in vitro fertilization. During the preoperative clinical examination and obtaining of anamnestic data, the patient denied symptoms of allergies to medicines and other substances. The dominant clinical manifestations of anaphylactic reaction were: hypotension, tachycardia, angioedema, bronchospasm, and delayed awakening following anesthesia. No visible changes in the appearance of the skin, such as erythema or urticaria have been observed. Proper clinical observation and adequate intraoperative monitoring led to rapid diagnosis and significantly reduced the time interval from the onset of anaphylaxis to the beginning of treatment and reanimation procedures.

Grape Seed Polyphenols and Fatty Acids of Autochthonous Prokupac Vine Variety from Serbia.

Grape pomace (grape skin, seeds, and stems) represents a valuable source of bioactive compounds, thus the interest in making use of these wine waste products is increasing. Prokupac is an autochthonous Serbian variety of black grape with a long tradition in production of red wine. Identification of the superficial polyphenolic compounds by LC/MS revealed presence of 19 compounds including hydroxybenzoic acid derivatives, ellagic acid derivatives, flavan-3-ol monomers, proanthocyanidins, and flavonols. Catechin and epicatechin together with proanthocyanidins were the most abundant compounds and the highest content of phenolic compounds was determined in Prokupac clones 43/1, 40/1, and 40/2. Grape seed oil consisted of dominantly UFA (87-95 %) where methyl linoleate was the most abundant in all samples (69-81 %). Palmitic (3-8 %) and stearic acid (2-4 %) methyl esters were dominant SFA. Prokupac clone 43/3 was the most abundant in UFA (95 %) with the lowest percentage of SFA (5 %), while clones 41/1 and 43/5 had the lowest percentage of UFA (87 %) and the highest content of SFA (13 %). Favorable chemical profile of Prokupac clone seeds implicates its potential to be used as a raw material in further processing and possibility to be included as one of the quality parameters in further selection of the most interesting Prokupac clone.

The relationship of early recurrence of atrial fibrillation and the 3-month integrity of the ablation lesion set.

Early recurrence of atrial fibrillation (ERAF) after catheter-ablation (CA) can be a transient phenomenon due to inflammation, or a harbinger of late AF recurrence due to CA lesion (re)conduction. We studied the relationship between ERAF and the 3-month CA lesions integrity. Forty one consecutive AF patients who underwent a pulmonary vein isolation (PVI), roof line (RL) and mitral isthmus line (MIL) CA were enrolled. At 3 months all patients underwent invasive assessment of the lesion set integrity irrespective of ERAF. The PVI, RL and MIL ablation was successful in 100.0%, 95.1% and 82.9% patients, respectively. At the 3-month remapping, a gap in PVI-lesion(s), RL or MIL was identified in 61.0%, 31.7% and 36.6% patients, respectively. Patients with (n = 17, 41.5%) compared to those without ERAF (n = 24) had a significantly higher rate of any PV-reconnection (88.2% vs. 41.7%), the right PV(s)-reconnection (82.5% vs. 29.2%) and the RL gap (52.9% vs. 16.7%), as well as a higher number of reconnected right PVI-segments, all p < 0.05. On multivariate analysis, only the number of reconnected right PVI-segments was associated with ERAF (OR 4.26, p = 0.004). The ERAF following PVI + RL + MIL ablation was significantly related to 3-month PV-reconnections and the presence of RL gaps.

Persistency of left atrial linear lesions after radiofrequency catheter ablation for atrial fibrillation: Data from an invasive follow-up electrophysiology study.

BACKGROUND: Data on the roof line (RL) and mitral isthmus line (MIL) reconnections after atrial fibrillation (AF) catheter ablation (CA) are scarce. OBJECTIVE: We studied the RL and MIL completeness and localization of reconnection sites in consecutive patients after their first-ever AF-CA. METHODS: We prospectively included 41 consecutive AF patients who underwent predefined lesion sets of two circumferential lines (CLs) for ipsilateral pulmonary vein isolation (PVI) combined with a RL and lateral MIL. Three months after CA, all patients underwent invasive follow-up procedure for line persistency evaluation, irrespective of clinical outcome. RESULTS: At the time of index ablation, PVI-CLs, RL, and MIL was completed in 41 (100%), 39 (95%), and 34 (83%) of patients, respectively. At the 3-month follow-up procedure, reconnections of PVI-CLs, RL, and MIL were found in 61% (25/41), 28% (11/39), and 24% (8/34) of patients, respectively. The 3-month reconnections were located commonly in the anterior and posterior PVI-CL segments, and rarely in the right third of RL and in the posterior part of MIL. The 3-month reconnections were rarely seen at the sites of acute reconnections during index procedure (6%, 20%, and 25% of the PVI-CL segments, RL segments, and MIL segments, respectively). CONCLUSIONS: To our knowledge, this is the first study systematically investigating the reconnection of standardized left atrium linear lesions such as RL and MIL after RF-CA for AF in consecutive patients. The RL and MIL 3-month reconnection rates were relatively low (28% and 24%), with poor anatomical concordance between the sites with acute and 3-month reconnections.

Prediction of very late arrhythmia recurrence after radiofrequency catheter ablation of atrial fibrillation: The MB-LATER clinical score.

Reliable prediction of very late recurrence of atrial fibrillation (VLRAF) occuring >12 months after catheter ablation (CA) in apparently "cured" patients could optimize long-term follow-up and modify decision-making regarding the discontinuation of oral anticoagulant therapy. In a single-centre cohort of consecutive patients post radiofrequency AFCA, we retrospectively derived a novel score for VLRAF prediction. Of 133 consecutive post AFCA patients (mean age 56.9 ± 11.8 years, 63.9% male, 69.2% with paroxysmal AF) who were arrhythmia-free at 12 months (excluding 3-month "blanking period"), 20 patients expirienced a VLRAF during a 29.1 ± 10.1-month follow-up, with a 3-year cumulative VLRAF rate of 31.1%. The MB-LATER score (Male, Bundle brunch block, Left atrium ≥47 mm, Type of AF [paroxysmal, persistent or long-standing persistent], and ER-AF = early recurrent AF), had better predictive ability for VLRAF (AUC 0.782) than the APPLE, ALARMc, BASE-AF2, CHADS2, CHA2DS2VASc or HATCH score (AUC 0.716, 0.671, 0.648, 0.552, 0.519 and 0.583, respectively), resulted in an improved net reclassification index (NRI) of 48.6-95.1% and better identified patients with subsequent VLRAF using decision-curve analysis (DCA). The MB-LATER score provides a readily available VLRAF risk assessment, and performs better than other scores. Validation of the MB-LATER score in other cohorts is underway.

Management and Outcome of Periprocedural Cardiac Perforation and Tamponade with Radiofrequency Catheter Ablation of Cardiac Arrhythmias: A Single Medium-Volume Center Experience.

INTRODUCTION: Cardiac tamponade (CT) is a life-threatening complication of radiofrequency ablation (RFA). The course and outcome of CT in low-to-medium volume electrophysiology centers are underreported. METHODS: We analyzed the incidence, management and outcomes of CT in 1500 consecutive RFAs performed in our center during 2011-2016. RESULTS: Of 1500 RFAs performed in 1352 patients (age 55 years, interquartile range: 41-63), 569 were left-sided procedures (n = 406 with transseptal access). Conventional RFA or irrigated RFA was performed in 40.9% and 59.1% of procedures, respectively. Ablation was performed mostly for atrioventricular nodal reentrant tachycardia (25.4%), atrial fibrillation (AF; 18.5%), atrial flutter (18.4%), accessory pathway (16.5%) or idiopathic ventricular arrhythmia (VA; 12.3%), and rarely for structural VA (2.1%). CT occurred in 12 procedures (0.8%): 10 AF ablations, 1 idiopathic VA and 1 typical atrial flutter ablation. Factors significantly associated with CT were older age, pre-procedural oral anticoagulation, left-sided procedures, transseptal access, AF ablation, irrigated RFA and longer fluoroscopy time (on univariate analysis), and AF ablation (on multivariable analysis). The perforation site was located in the left atrium (n = 7), right atrium (n = 3), or in the left ventricle or coronary sinus (n = 1 each). Upon pericardiocentesis, two patients underwent urgent cardiac surgery because of continued bleeding. There was no fatal outcome. During the follow-up of 19 ± 14 months, eight patients were arrhythmia free. CONCLUSION: Incidence of RFA-related CT in our medium-volume center was low and significantly associated with AF ablation. The outcome of CT was mostly favorable after pericardiocentesis, but readily accessible cardiothoracic surgery back-up should be mandatory in RFA centers.

Analysis of intracranial hemorrhage grade in preterm singleton pregnancies delivered vaginally or by cesarean section.

BACKGROUND/AIM: Preterm birth is the leading cause of neonatal mortality. Periventricular hemorrhage-intraventricular hemorrhage (PVH-IVH) remains a significant cause of both morbidity and mortality in infants prematurely born. The aim of the study was to evaluate the perinatal outcome regarding IVH of premature babies according to the mode of delivery. METHODS: A total of 126 women in preterm singleton pregnancies with vertex presentation and 126 neonates weighted from 750 g to 1,500 g at birth were enrolled. The outcomes of 64 neonates born vaginally were compared to 62 neonates born by cesarean section. RESULTS: There was no significant difference in the incidence of IVH among both groups. CONCLUSION: Our data is consistent with the hypothesis that the mode of delivery does not influence IVH and consenquently perinatal outcome in preterm neonates.

[Spontaneous intra-abdominal bleeding in twin pregnancy--case report].

INTRODUCTION: Spontaneous rupture of utero-ovarian vessels is a rare cause of haemoperitoneum in pregnancy, leading to significant maternal and foetal morbidity and mortality. Aetiopathogenesis of this condition is still unclear. Establishing clinical diagnosis of this condition is difficult, but very important. Clinical symptoms are nonspecific, and the diagnosis is usually made at laparotomy. CASE OUTLINE: We report a case of spontaneous haematoperitoneum in the third trimester of twin pregnancy. Differential diagnosis included uterine rupture and placental abruption. Due to the deteriorated condition of the patient, it was decided to perform laparotomy which established the diagnosis of ruptured venous varices on the posterior uterine wall. Delivery was performed by caesarean section. The postoperative period was uneventful. CONCLUSION: The clinical presentation of spontaneous rupture of utero-ovarian blood vessels is not specific and clinical examination and ultrasonographic scanning may be insufficient for diagnosis. Once the diagnosis of spontaneous haematoperitoneum in pregnancy is established, emergency laparotomy is indicated. Following caesarean delivery, it is necessary to establish surgical haemostasis. There are some authors who suggest leaving the pregnancy intact in cases when the foetus is not viable, although one must have in mind the possibility of recurrent bleeding. The safety of this procedure requires further investigation. It is necessary to have in mind the possibility of blood vessel rupture in all cases of abdominal pain and hypotension of unknown origin during pregnancy.

Decreasing incidence of urothelial cancer in a Balkan endemic nephropathy region in Serbia. A surgery based study from 1969 to 1998.

The incidence of upper urothelial tumors (UUT) and bladder tumors associated to Balkan endemic nephropathy (BEN) in the region of South Morava River in Serbia, in the 30-year period, was studied. A total of 575 urothelial neoplasms during 10-year period (1989-1998) was analyzed and compared to 659 urothelial neoplasms in the period from 1969 to 1988. UUT had 11.2-fold increased incidence in endemic than in nonendemic areas, however, this was far less than in the period from 1969 to 1988, when they were 57.1 times more frequent. Bladder tumors were 2.3 times more frequent in endemic than in nonendemic areas, but 11.9 times in the previous study from 1969 to 1988. Neoplasms from the area of BEN, regardless of their location, were not histologically different from the neoplasms out of endemic areas. Similarly to the previous reports that BEN looks like a disease that disappears, this is demonstrated also for urothelial tumors, which are the most frequent associated diseases.

[Preoperative radiologic evaluation of tumors of the renal parenchyma]. / Preoperaciona radioloska procena tumor parenhima bubrega.

Renal cell carcinoma is frequently a matter of urological interest. In recent years there were significant improvements regarding the earlier diagnosis, more precise preoperative staging and appropriate therapy. One hundred patients (42-78 years old) with the preoperative diagnosis of renal cell carcinoma were analyzed. Preoperative radiological evaluation included: transabdominal ultrasound, intravenous urography, computer-assisted tomography, and angiography. In all patients after radical nephrectomy pathohistological diagnosis was established and patients with the confirmed renal cell carcinoma tumour staging was performed. All histological findings were compared with the preoperative results of radiological examinations. Reliability of all of them is separately determined. Our results confirmed that the most efficient method of preoperative staging was computer-assisted tomography (accuracy 93%). Diagnostic methods that were previously used like intravenous urography and angiography, were not useful for routine diagnostic purposes. Ultrasound is a precise but not an enough informative diagnostic tool (accuracy 87%). Combine used of both ultrasound and contrast computer-assisted tomography is cost-effective, and an enough precise combination for everyday use.