Search

Introduction Pain assessment in children is crucial in managing postoperative analgesia; it is therefore necessary to determine the most accurate tool for assessing pain in children. The aim of this study was to evaluate the correlation between skin conductance measurements and self-reporting pain scales in children after otolaryngology procedures. Materials and methods Thirty-three children (N=33) were assessed for eligibility for the research. Postoperative pain was assessed using the Visual Analogue Scale; the Wong-Baker Faces Pain Rating Scale; the Face, Legs, Activity, Cry, and Consolability scale; and a skin conductance algesimeter. The postoperative pain was measured 1 and 2 hours after the surgery. Results There was no statistically significant correlation between self-reported pain scores and the skin conductance fluctuations in the children studied, regardless of gender or age. A statistically significant correlation was found between the existing subjective pain scales in children. Conclusions The skin conductance measurements do not provide an additional reliable tool for assessing pain in patients after otolaryngological procedures. The existing self-reported pain scales are sufficient to assess postoperative pain in children.

Single-nucleotide polymorphisms in the human juxtaposed with another zinc finger protein 1 ( JAZF1 ) gene have repeatedly been associated with both type 2 diabetes (T2D) and height in multiple genome-wide association studies (GWAS); however, the mechanism by which JAZF1 causes these traits is not yet known. To investigate the possible functional role of JAZF1 in growth and glucose metabolism in vivo, we generated Jazf1 knockout (KO) mice and examined body composition and insulin sensitivity both in young and adult mice by using 1 H-nuclear magnetic resonance and hyperinsulinemic-euglycemic clamp techniques. Plasma concentrations of insulin-like growth factor 1 (IGF-1) were reduced in both young and adult Jazf1 KO mice, and young Jazf1 KO mice were shorter in stature than age-matched wild-type mice. Young Jazf1 KO mice manifested reduced fat mass, whereas adult Jazf1 KO mice manifested increased fat mass and reductions in lean body mass associated with increased plasma growth hormone (GH) concentrations. Adult Jazf1 KO manifested muscle insulin resistance that was further exacerbated by high-fat diet feeding. Gene set enrichment analysis in Jazf1 KO liver identified the hepatocyte hepatic nuclear factor 4 alpha (HNF4α), which was decreased in Jazf1 KO liver and in JAZF1 knockdown cells. Moreover, GH-induced IGF-1 expression was inhibited by JAZF1 knockdown in human hepatocytes. Taken together these results demonstrate that reduction of JAZF1 leads to early growth retardation and late onset insulin resistance in vivo which may be mediated through alterations in the GH-IGF-1 axis and HNF4α.

Single-nucleotide polymorphisms in the human juxtaposed with another zinc finger protein 1 (

Background In the era of potent P2Y12 inhibitors, according to current guidelines on ST-segment elevation myocardial infarction (STEMI), treatment with glycoprotein IIb/IIIa inhibitors (GPI) should be limited to selected bail-out or highly thrombotic situations. Similarly, aspiration thrombectomy (AT) is downgraded in current guidelines for very selective but not routine usage. Both recommendations make the treatment of thrombus containing lesions somewhat defensive, underlining the need for an individualized approach to STEMI patients. However, data concerning current clinical practice of such approach are limited. Purpose We examined the prevalence, procedural characteristics, and predictors of GPI administration and AT usage in all-comers contemporary STEMI patients referred to primary PCI in Poland. Methods We focused on 116,873 consecutive STEMI patients undergoing primary PCI in Poland between 2015 and 2020. Results GPIs were administered in 29.3% of patients and AT was used in 11.6%, with combined treatment with GPI and AT in 6.1% of patients. There was a slight trend towards a decrease in GPI and AT usage during the analyzed years. On the opposite, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5% in 2015 to 48.1% in 2020 (Figure 1). Patients with periprocedural GPI administration and combined strategy with GPI and AT were younger, more often men, with history of smoking and presented with cardiogenic shock on admission. They were less likely to have diabetes, chronic kidney disease and previous stroke. Occluded infarct-related artery in baseline angiography and no-reflow during PCI were the strongest independent predictors of GPI administration and combined usage of GPI and AT in a multivariate logistic regression model. Similarly, administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies (see table for details). Conclusions Despite the rapid growth of potent P2Y12 inhibitors usage in Poland in recent years, GPI and AT are selectively used at a stable level during primary PCI in highly thrombotic STEMI lesions. Funding Acknowledgement Type of funding sources: None.

Introduction There are conflicting data on the clinical outcomes of percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) based on time of intervention. Concerns have been postulated regarding equally effective in-hospital outcomes for STEMI patients treated with PCI during normal working hours as compared to group treated off-hours. Purpose The aim of this study was to assess clinical outcomes in “real-world” patients with STEMI treated with PCI during off-hours and regular hours of work. Methods To avoid possible bias related to the non-randomized design, a propensity score was calculated to compare off- and on-hours groups. The study group consisted of 37, 469 matched pairs in STEMI treated with PCI and stent implantation between 2014 and 2018 during regular hours (weekdays 7:00 AM to 16:59 PM) and off-hours (weekdays between 17:00 PM and 06:59AM, weekends, and holidays) in 151 tertiary invasive cardiology centers in Poland (the ORPKI Polish National Registry). Results No differences were reported between both groups in baseline characteristics after the propensity score match (PSM). There were no differences in time from pain to first contact (p=0.2) and door to balloon time between both groups (p=0.7). After PSM higher radiation dose was observed in off-hours group (1055.18 (±1006.52) vs. 1081.59 (±1003.25)[mGy]; p=0.001). However, there was no difference in total amount of contrast (on-hours vs. off-hours: 175.69 (±74.71) vs. 176.48 (±74.41)[ml]; p=0.1, respectively). Similar rate of periprocedural complications was observed between both groups of patients, includind stroke, access-site-related bleeding, allergic reaction and coronary artery perforation. However, procedures performed during off-hours were associated with higher incidence of periprocedural death (1.17% (439) vs. 1.49% (559); p=0.001) and periprocedural cardiac arrest (1.76% (658) vs.1.97% (740); p=0.001) as compared to PCI conducted within normal working hours. Conclusions Percutaneous coronary intervention in STEMI performed durgin off-hours might be associated with higher rate of periprocedural mortality and higher radiation dose as compared to procedures conducted during regular working hours. Funding Acknowledgement Type of funding source: None

Repressive KRAB domain-containing zinc-finger proteins (KRAB-ZFPs) are abundant in mammalian genomes and contribute both to the silencing of transposable elements (TEs) and to the regulation of developmental stage- and cell type-specific gene expression. Here we describe studies of zinc finger protein 92 (Zfp92), an X-linked KRAB-ZFP that is highly expressed in pancreatic islets of adult mice, by analyzing global Zfp92 knockout (KO) mice. Physiological, transcriptomic and genome-wide chromatin binding studies indicate that the principal function of ZFP92 in mice is to bind to and suppress the activity of B1/Alu type of SINE elements and modulate the activity of surrounding genomic entities. Deletion of Zfp92 leads to changes in expression of select LINE and LTR retroelements and genes located in the vicinity of ZFP92-bound chromatin. The absence of Zfp92 leads to altered expression of specific genes in islets, adipose and muscle that result in modest sex-specific alterations in blood glucose homeostasis, body mass and fat accumulation. In islets, Zfp92 influences blood glucose concentration in postnatal mice via transcriptional effects on Mafb, whereas in adipose and muscle, it regulates Acacb, a rate-limiting enzyme in fatty acid metabolism. In the absence of Zfp92, a novel TE-Capn11 fusion transcript is overexpressed in islets and several other tissues due to de-repression of an IAPez TE adjacent to ZFP92-bound SINE elements in intron 3 of the Capn11 gene. Together, these studies show that ZFP92 functions both to repress specific TEs and to regulate the transcription of specific genes in discrete tissues.

A sustained increase in intracellular Ca2+ concentration (referred to hereafter as excitotoxicity), brought on by chronic metabolic stress, may contribute to pancreatic β-cell failure. To determine the additive effects of excitotoxicity and overnutrition on β-cell function and gene expression, we analyzed the impact of a high-fat diet (HFD) on Abcc8 knockout mice. Excitotoxicity caused β-cells to be more susceptible to HFD-induced impairment of glucose homeostasis, and these effects were mitigated by verapamil, a Ca2+ channel blocker. Excitotoxicity, overnutrition, and the combination of both stresses caused similar but distinct alterations in the β-cell transcriptome, including additive increases in genes associated with mitochondrial energy metabolism, fatty acid β-oxidation, and mitochondrial biogenesis and their key regulator Ppargc1a. Overnutrition worsened excitotoxicity-induced mitochondrial dysfunction, increasing metabolic inflexibility and mitochondrial damage. In addition, excitotoxicity and overnutrition, individually and together, impaired both β-cell function and identity by reducing expression of genes important for insulin secretion, cell polarity, cell junction, cilia, cytoskeleton, vesicular trafficking, and regulation of β-cell epigenetic and transcriptional program. Sex had an impact on all β-cell responses, with male animals exhibiting greater metabolic stress-induced impairments than females. Together, these findings indicate that a sustained increase in intracellular Ca2+, by altering mitochondrial function and impairing β-cell identity, augments overnutrition-induced β-cell failure.

Background The COVID-19 pandemic negatively affected access to health-care system and timeline of treatment. The fear of contamination might potentially forbear from accessing the emergency system.mFurthermore, pandemic-specific protocols require additional time to prepare medical stuff and catheterization laboratory before procedure. Thus, patients with ST-segment elevation myocardial infarction (STEMI) might be exposed to a longer delay for revascularization and higher risk of mortality. Purpose The aim of this study was to evaluate treatment delay and clinical outcomes in COVID-19 positive and negative patients with STEMI treated with percutaneous coronary intervention (PCI) during on- and off hours. Methods All consecutive patients with STEMI treated with PCI and stent implantation between 1st March 2020 and 31st December 2020 were enrolled into analysis. To overcome potential bias related to the non-randomized design a propensity score match (PSM) was used to compare COVID-19 positive and negative patients for both working frames hours. The study group consisted of 877 matched pairs treated during regular hours (everyday 7:00AM-16:59PM) and 418 matched pairs with PCI performed during off-hours (everyday 17:00PM and 06:59AM) in 151 tertiary invasive cardiology centers in Poland (the ORPKI Polish National Registry). Results After PSM there were no differences between COVID-19 positive and negative patients in baseline characteristics during both on- and off-hours. However, patients diagnosed with COVID-19 were admitted with cardiac arrest more frequently as compared to COVID-19 negative patients during regular working hours (180 (20.5%) vs. 64 (7.30%); p=0.001). There were no differences in radiation doses and total amount of contrast between both groups. Similarly, no differences in rate of periprocedural complications were observed despite of time of intervention, including stroke, access-site-related bleeding, allergic reaction and coronary artery perforation. Furthermore, there were no differences in periprocedural mortality between both groups (on-hours: COVID-19 negative vs. COVID-19 positive: 17 (1.9%) vs. 11 (1.3%),p=0.3; off-hours: COVID-19 negative vs. COVID-19 positive: 4 (1.0%) vs. 7 (1.7%),p=0.5). However, COVID-19 positive patients were exposed to longer time from first medical contact to angiography during both on-hours (133.76 (±137.10) vs. 117.14 (±135.83) [min]; p=0.001) and off-hours (148.08 (±201.56) vs. 112.19 (±138.72) [min]; p=0.003). Time from pain to first medical contact remained similar during both working frame hours (On-hours and off-hours, respectively: p=0.7 and p=0.9). Conclusions Patients diagnosed with COVID-19 might experience a longer time from first medical contact to revascularization. There was no impact of COVID-19 diagnosis on rate of periprocedural mortality or periprocedural complication, irrespective of time of intervention. System-level changes might be crucial to improve health-care during COVID-19 pandemic. Funding Acknowledgement Type of funding sources: None.

Aims This survey conducted by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and ESC Working Group on Pulmonary Circulation & Right Ventricular Functioncollected information on current practices in catheter-directed treatment (CDT) of acute pulmonary embolism (PE) among cardiology intervention centers in European countries. Methods and results Responses from 157 Catheterization laboratories (Cath Lab) representing European countries were collated and analyzed.Sixty seven centers (43%) centers reported application of CDT in PE patients. Almost all centers performing CDT (96%) provided 24/7 service and had experience with a wide spectrum of percutaneous interventions including those for the treatment of structural heart diseases; 53% of the Cath labs utilizing CDT were located in teaching hospitals, and involved 5 to 10 interventional cardiologists performing more than 600 coronary procedures per year. The survey showed a rapid increase in CDT use in European countries after 2015 (45 out of 67 centers). Over 60% of responding centers performed 5–10 CDT procedures per year. It was estimated that 24 patients were treated with CDT per center on a yearly base. The majority of centers (80.3%) indicated that CDT is used in high-risk PE patients, while 38% also apply CDT to intermediate high risk PE. The survey revealed that pigtail catheters are most commonly used for CDT (49%), while dedicated systems such as AngioJet, Indigo and EKOS were reported to be used in 25%, 23.81% and 20.24% of the centers, respectively. Local thrombolysis during CDT was used in 71% of the procedures. More than 60% of the responders indicated that according to their expert opinion CDT will be routinely used in PE patients in the future. However, they stressed the need for randomized trials to evaluate the safety and efficacy of CDT and determine the patients that would benefit most. Conclusions According to the survey, use of CDT in patients with PE is increasing over time. Currently, it is mostly but not exclusively applied to patients with high-risk PE. The respondents indicated the need for high-quality randomized trials to establish the optimal indication for CDT and further standardize the use of the available techniques. Funding Acknowledgement Type of funding sources: None.

Insm1, Neurod1, and Pax6 are essential for the formation and function of pancreatic endocrine cells. Here, we report comparative immunohistochemical, transcriptomic, functional enrichment, and RNA splicing analyses of these genes using gene knock-out mice. Quantitative immunohistochemical analysis confirmed that elimination of each of these three factors variably impairs the proliferation, survival, and differentiation of endocrine cells. Transcriptomic analysis revealed that each factor contributes uniquely to the transcriptome although their effects were overlapping. Functional enrichment analysis revealed that genes downregulated by the elimination of Insm1, Neurod1, and Pax6 are commonly involved in mRNA metabolism, chromatin organization, secretion, and cell cycle regulation, and upregulated genes are associated with protein degradation, autophagy, and apoptotic process. Elimination of Insm1, Neurod1, and Pax6 impaired expression of many RNA-binding proteins thereby altering RNA splicing events, including for Syt14 and Snap25, two genes required for insulin secretion. All three factors are necessary for normal splicing of Syt14, and both Insm1 and Pax6 are necessary for the processing of Snap25. Collectively, these data provide new insights into how Insm1, Neurod1, and Pax6 contribute to the formation of functional pancreatic endocrine cells.

To gain a deeper understanding of pancreatic β-cell development, we used iterative weighted gene correlation network analysis to calculate a gene co-expression network (GCN) from 11 temporally and genetically defined murine cell populations. The GCN, which contained 91 distinct modules, was then used to gain three new biological insights. First, we found that the clustered protocadherin genes are differentially expressed during pancreas development. Pcdhγ genes are preferentially expressed in pancreatic endoderm, Pcdhβ genes in nascent islets, and Pcdhα genes in mature β-cells. Second, after extracting sub-networks of transcriptional regulators for each developmental stage, we identified 81 zinc finger protein (ZFP) genes that are preferentially expressed during endocrine specification and β-cell maturation. Third, we used the GCN to select three ZFPs for further analysis by CRISPR mutagenesis of mice. Zfp800 null mice exhibited early postnatal lethality, and at E18.5 their pancreata exhibited a reduced number of pancreatic endocrine cells, alterations in exocrine cell morphology, and marked changes in expression of genes involved in protein translation, hormone secretion and developmental pathways in the pancreas. Together, our results suggest that developmentally oriented GCNs have utility for gaining new insights into gene regulation during organogenesis.

Background Reliable coronary physiology assessment with pressure derived indexes in patients with aortic stenosis (AS) rises problems due to its complex nature. Recent data suggest that fractional flow reserve (FFR) may underestimate intermediate coronary stenosis in a presence of AS whereas instantaneous wave-free ratio (iFR) values may remain similar after treatment of AS. Furthermore, both indices has not been validated yet in AS. Aim We aimed to find a thresholds for coronary ischemia in the setting of aortic Material and methods The functional significance of 416 coronary lesions was investigated with iFR and FFR measurements in 221 AS patients. The iFR-FFR diagnostic agreement has been tested using the cut-off value for iFR of 0.89. Results Mean value of %DS was 58.6±13.4%, FFR was 0.85±0.07 and iFR – 0.90±0.04. FFR ≤0.80 was measured in 26.0% of interrogated vessels, iFR ≤0.89 – in 33.2%. The correlation between iFR and FFR was good (r=0.83, p Conclusion In the presence of AS, FFR had good agreement with iFR values. However, FFR threshold for predicting iFR below 0.89 may be different from a standard threshold and that should be taken into account while assessing coronary physiology in the setting of AS. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science Center

Background The functional assessment of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) has been barely examined so far, and the best strategy to physiologically investigate the relevance of coronary stenosis in this specific setting of patients remains undetermined. The aim of the study is to compare the diagnostic performance of instantaneous wave-free ratio (iFR), quantitative flow ratio (QFR) and fractional flow reserve (FFR) in patients with severe AS. Methods The functional significance of 416 coronary lesions was investigated with iFR, FFR and QFR measurements in 221 AS patients. The iFR-FFR and QFR-FFR diagnostic agreement has been tested using the conventional 0.80 FFR cut-off. Results Mean value of FFR was 0.85±0.07; iFR – 0.90±0.04; QFR – 0.84±0.07. The correlation between iFR and FFR was good (r=0.83, p Conclusions In the presence of severe AS, iFR and QFR had good agreement with FFR values for assessment of borderline coronary lesions. However, iFR threshold for predicting FFR below 0.8 may be different from a standard value of 0.89. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science Centre

Background Previously published studies assessing the time effect of primary percutaneous intervention (PCI) on long-term clinical outcomes in an overall group of patients with acute coronary syndromes has been widely investigated. It has been suggested that night-time admission may negatively influence long-term overall mortality. Patients treated within the left main coronary artery (LMCA) belong a narrow group of high-risk procedures that require an operator and a team with high skills. Purpose The aim of the presented study was to assess the relationship between the time of pPCI (day- vs. night-time) and overall mortality among patients treated due to AMI within the LMCA. Methods This observational study was performed on 443,805 patients hospitalised due to non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI). Patients were prospectively enrolled between January 2006 and December 2018 in the ongoing Polish Registry of Acute Coronary Syndromes (PL-ACS). From the overall group of patients, the authors selected 5,404 patients treated within the LMCA. After taking exclusion criteria into consideration, the patients were divided according to time of PCI treatment: daytime hours (7:00 a.m.-10:59 p.m.) – 2,809 patients and night-time hours (11:00 p.m. - 6.59 a.m.) – 473 patients. Results Patients treated during night-time and daytime did not differ significantly in age (70.79 [61.52–79.73] vs. 69.73 [60.8–78.82] years, p=0.13) or gender – males (67.6% vs. 67.0%, p=0.79). Patients treated during daytime presented with significantly higher rate of STEMIs (67.2% vs. 49.9%) and lower rate of NSTEMIs (32.8% vs. 50.1%) in comparison to those treated during night-time (p Conclusions The time of pPCI (day- vs. night-time) in patients with AMI and treated within the LMCA is related to the overall 30-day and 12-month survival which is poorer in those treated during the night-time. However, this relationship was not confirmed by multiple regression analysis and was not found to be significant among other stronger predictors. Funding Acknowledgement Type of funding source: None

To gain a deeper understanding of pancreatic β-cell development, we used iterative weighted gene correlation network analysis to calculate a gene co-expression network (GCN) from 11 temporally and genetically defined murine cell populations. The GCN, which contained 91 distinct modules, was then used to gain three new biological insights. First, we found that the clustered protocadherin genes are differentially expressed during pancreas development. Pcdhγ genes are preferentially expressed in pancreatic endoderm, Pcdhβ genes in nascent islets, and Pcdhα genes in mature β-cells. Second, after extracting sub-networks of transcriptional regulators for each developmental stage, we identified 81 zinc finger protein (ZFP) genes that are preferentially expressed during endocrine specification and β-cell maturation. Third, we used the GCN to select three ZFPs for further analysis by CRISPR mutagenesis of mice. Zfp800 null mice exhibited early postnatal lethality, and at E18.5 their pancreata exhibited a reduced number of pancreatic endocrine cells, alterations in exocrine cell morphology, and marked changes in expression of genes involved in protein translation, hormone secretion and developmental pathways in the pancreas. Together, our results suggest that developmentally oriented GCNs have utility for gaining new insights into gene regulation during organogenesis.

Background The aim of this study was to evaluate the safety and efficacy of the novel NovaCross microcatheter system in patients with ischemic heart disease due to coronary chronic total occlusions (CTO). Methods A total of 191 subjects between the ages of 25-80 years were recruited in 10 investigational sites. Each subject underwent a percutaneous coronary intervention (PCI) of a CTO lesion using the NovaCross microcatheter, equipped with expandable nitinol scaffolds to enhance guidewire penetration and crossing of the CTO lesion. The primary safety endpoint was procedural major adverse cardiac events [composite of death, myocardial infarction (MI), or urgent target vessel revascularization]. The primary efficacy endpoint was to assess the ability of the NovaCross microcatheter to successfully facilitate the placement of a guidewire beyond a native coronary CTO in the true vessel lumen. After the PCI, subjects remained in hospital until a 12-lead ECG and blood tests for cardiac biomarkers were taken at 3-6 h and 8-16 h post-procedure. Results No deaths, urgent revascularization, or urgent coronary artery bypass surgery were reported. The reported MI rate according to the protocol definition was 12.3%, and technical success was achieved in 75.3% of the subjects regardless of CTO procedure technique. In 89.2% of the subjects, the NovaCross succeeded in penetrating the proximal CTO cap, and in 25.8% of the subjects, the extendable portion of the NovaCross crossed the full length of the CTO lesion. Conclusions The NovaCross met both the primary safety endpoint and the primary efficacy endpoint. We, therefore, conclude that the device is well tolerated, effective, and could be easily adopted by interventional cardiologists.

Objectives The purpose of this study was to evaluate the outcomes of the novel Fantom coronary bioresorbable scaffold at 6 months. Background The Fantom sirolimus-eluting bioresorbable scaffold incorporates a unique proprietary iodinated, polycarbonate copolymer of tyrosine analogs that is radiopaque, with thin struts (125 μm) that facilitate device delivery and precise target lesion treatment. Methods The 6-month outcomes and performance of the Fantom scaffold were evaluated in 117 patients with single de novo native coronary artery lesions of length ≤20 mm and reference vessel diameter 2.5 to 3.5 mm. The primary angiographic endpoint was mean late lumen loss at 6 months measured by quantitative coronary angiography. Procedural outcomes were categorized as short-term technical success, short-term procedural success, and clinical procedural success. The primary clinical endpoint was major adverse cardiac events at 6 months, the composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR). Results Short-term technical success, short-term procedural success, and clinical procedural success were achieved in 96.6%, 99.1%, and 99.1% of patients, respectively. Mean 6-month in-stent late lumen loss was 0.25 ± 0.40 mm (n = 100). Binary restenosis was present in 2 patients (2.0%). Major adverse cardiac events within 6 months occurred in 3 patients (2.6%), including no deaths, 2 MIs, and 2 TLRs (1 patient had both an MI and TLR). Scaffold thrombosis occurred in 1 patient (0.9%). Conclusions The clinical results from 117 patients enrolled in cohort A of the multicenter FANTOM II (Safety & Performance Study of the FANTOM Sirolimus-Eluting Bioresorbable Coronary Scaffold) study demonstrate favorable 6-month outcomes of this novel device in the treatment of noncomplex coronary artery disease.

BACKGROUND Quantitative flow ratio (QFR) has been validated as an accurate surrogate of standard wire-based fractional flow reserve. The clinical and angiographic outcomes of the Fantom sirolimus-eluting bioresorbable coronary scaffold (BRS) have been previously studied and reported. We investigate the functional performance of the Fantom BRS. METHODS The FANTOM II trial prospectively enrolled 240 patients with stable coronary artery disease or unstable angina, of which 235 patients received the Fantom BRS and were included in the present analysis. We performed an independent serial QFR analysis of the target vessel at baseline, post-percutaneous coronary intervention (PCI), and at 6- or 9-month and 24-month follow-up, using a QFR threshold ≤0.80 to define functional ischemia. RESULTS QFR was analyzable in 178 patients at baseline, 185 post-PCI, 178 at 6- or 9-month follow-up, and 30 at 24-month follow-up. At baseline, 119 patients (66.9%) had a QFR ≤0.80, whereas 12 (6.5%) post-PCI, 13 (7.3%) at 6- or 9-month follow-up, and 3 (10.0%) at 24-month follow-up had a QFR ≤0.80. QFR improved from baseline to post-PCI, and decreased from post-PCI up to 24-month follow-up. During follow-up period, 28 patients (11.9%) had target vessel revascularization, of which 21 had analyzable QFR and 16 patients (76.1%) had QFR ≤0.80 at the time of revascularization. CONCLUSIONS Off-line serial QFR assessment demonstrated that around 30% patients did not have functionally significant lesions at baseline and the time with target vessel revascularization. PCI with the Fantom BRS improved functional ischemia with a slight decrease in QFR values over 24 months.

Introduction 2017 ESC Guidelines for the management of ST-elevation myocardial infarction (STEMI) patients have called for the assessment of the quality of care to establish measurable quality indicators in order to ensure that every patient with STEMI receives the best possible care. We investigated the quality indicators of health care services in Poland provided to STEMI patients. Methods The Polish Registry of Acute Coronary Syndromes (PL-ACS) is an ongoing, nationwide, multicenter, prospective, observational study of consecutively hospitalized patients with the whole spectrum of ACS in Poland. For the purpose of assessing quality indicators, we included 8,279 patients from the PL-ACS Registry hospitalized with STEMI between January 1 and December 31, 2018. Results All emergency medical services (EMS) are equipped with ECG/defibrillators. 408 of 8,279 patients (4.9%) arrived at PCI center by self-transport, 4,791 patients (57.9%) patients arrived at PCI center by direct EMS transport, and 2,900 patients (37.2%) were transferred from non-PCI facilities. Whilst 95.1% of STEMI patients arriving in the first 12 hours received reperfusion therapy, the rates of timely reperfusion were much lower (ranging from 39.4% to 55.0% for various STEMI pathways). 7,807 patients (94.3%) underwent PCI as a mode of primary reperfusion strategy. The median left ventricular ejection fraction (LVEF) was 46% and was assessed before discharge in 86.0% of patients. 489 of 8,279 patients (5.9%) died during hospital stay. Optimal medical therapy is prescribed in 50–85% of patients depending on various clinical settings. Only one in two STEMI patient is enrolled in a cardiac rehabilitation program at discharge. No patient-reported outcomes were recorded in the PL-ACS Registry. Figure 1 Conclusions The results of this study identified areas of healthcare systems that require solid improvement. These include prehospital ECG decision strategy, direct transport to PCI center, timely reperfusion, guidelines-based medical therapy (in particular in patients with heart failure), referral to cardiac rehabilitation/secondary prevention programs. More importantly, we recognized an urgent need for the initiation of recording quality indicators associated with patient-reported outcomes.

Introduction Radial approach (RA) for percutaneous coronary intervention (PCI) is associated with reduced mortality and access site complications. The routine use of the RA in patients should be strongly considered, keeping in mind the learning curve associated with the technique. However, promotion of RA may interfere with the equally important goal of maintaining proficiency in the femoral approach (FA), which is essential in a variety of procedures as well as when RA fails. There is possible risk of higher rate of complications in PCI with FA performed by operators mainly using radial artery as access site. Purpose The aim of this study was to evaluate impact of experience and proficiency with RA for clinical outcomes on PCI via FA in “real-world” patients with acute coronary syndrome (ACS). Methods A total of 539 invasive cardiologists performing PCI in 151 invasive cardiology centers on the Polish territory between 2014 and 2017 were included in study analysis. Proficiency threshold has been set at >400 procedures during four consecutive years per individual operator. They were categorized to quartiles according to total volume of radial artery utilization during all PCIs. Procedures performed on patients with Killip-Kimball class IV on admission to catheterisation laboratory were excluded from analysis. Results The most of the operators performed >75% of all procedures via radial artery (326 (60.5%)), 112 (20.8%) used RA in 50–75% of cases, 67 (12.4%) in 25–50% of all PCIs and only 34 (6.3%) invasive cardiologist were using RA in less than 25% of all procedures. Mortality during PCI via FA was higher in group of invasive cardiologist with >75% of all procedures performed with radial access (>75% vs. 50–75% vs. 25–50% vs. 75% vs. 50–75% vs. 25–50% vs. Conclusions Higher experience in radial access might be linked to worse outcome in PCI via FA in ACS settings. Femoral artery is important vascular approach and should not be abandoned while learning procedures with radial artery utilization. Acknowledgement/Funding None

Introduction The use of the radial approach (RA) for percutaneous coronary intervention (PCI) has gradually increased. Several studies demonstrated that radial artery is associated with significant reduction in major adverse cardiac events for both coronary angiography and PCI in acute coronary syndrome (ACS). However, it is still unclear if the side of RA has influence on clinical outcomes in an all-comer population in ACS settings. Purpose We sought to evaluate safety, feasibility, and clinical outcomes of right radial approach (RRA) compared to left radial approach (LRA) during PCI in “real-world” patients with ACS. Methods A total of 234,087 consecutive patients with ACS treated with PCI and stent implantation via radial approach between 2014 and 2017 in 151 invasive cardiology centers on the Polish territory. Data was based on the ORPKI Polish National Registry. Patients treated with RRA and LRA were compared using a propensity score analysis to avoid possible selection bias. The analysis was done in an “as-treated” manner. Results Procedure was conducted using RRA and LRA in 180,378 (77.1%) and 53,709 (22.9%) patients, respectively. After propensity score matching higher total amount of contrast (174.28 (±75.56) vs. 166.95 (±70.57) [ml]; P=0.001) and radiation doses were reported in PCI with left radial artery utilization (1210.21 (±1003.53) vs. 1054.07 (±1024.17) [mGy]; p=0.001). No differences were observed between RRA and LRA in rate of periprocedural adverse events such as myocardial infarction (0.08% vs. 0.08%; p=0.9) stroke (0.02% vs. 0.01%; p=0.1), no-reflow phenomenon (0.64%vs. 0.56%; p=0.1) and death (0.25% vs. 0.24%; p=0.7). A trend towards a lower rate of access-site-related bleeding during PCI was observed in RRA group (0.08% vs. 0.05%; p=0.066). Coronary artery perforation (0.21% vs. 0.16%; p=0.05) and cardiac arrest (0.56% vs 0.42%; p=0.01) were reported more often during PCI conducted with LRA. Conclusions Both radial approaches seems to be equally effective in the setting of PCI in ACS. However, utilization of left radial artery was associated with trend toward increased risk of access-site bleeding and higher rate of periprocedural complications as compared to RRA. Higher amount of contrast and radiation doses used in LRA procedures might be equivalent of generally lower experience with this access site. Acknowledgement/Funding None

Background The safety and efficacy of the ABSORB scaffold in ACS patients remain unclear. The COMPARE-ABSORB trial compares the ABSORB to the Xience stent in lesions and patients at high risk for restenosis Patients with STEMI and urgent PCI for non-STEMI were not excluded. Methods Patients included in the COMPARE-ABSORB trial undergoing PCI for ACS were eligible. Predefined implantation techniques for ABSORB was mandatory. Primary endpoint is target lesion failure (TLF) at 1 year, defined as a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularization. Results Of 1670 patients, 842 were treated for ACS. At 1-year, TLF occurred in 22 patients (5.0%) of the ABSORB group and in 14 patients (3.5%) of the Xience group (HR 1.44%; 95% CI 0.74%-2.82%, P=0.284). Definite device thrombosis occurred in 9 patients (2.0%) of the ABSORB group and in 2 patients (0.5%) of the Xience group (HR 4.10%; 95% CI 0.89%-18.9%, P=0.071). Baseline characteristics ABSORB (n=442) XIENCE (n=400) Age, years (SD) 60.7 (9.6) 61.3 (9.1) Male 350/442 (79.2%) 313/400 (78.3%) Current smoker 159/439 (36.2%) 126/397 (31.7%) Diabetes mellitus 152/440 (34.5%) 138/399 (34.6%) Hypertension 298/442 (67.4%) 266/400 (66.5%) Hypercholesterolemia 255/442 (57.7%) 232/400 (58.0%) Family history of coronary artery disease 147/442 (33.3%) 103/400 (25.8%) Previous MI 61/442 (13.8%) 67/400 (16.8%) Established Peripheral Vascular Disease 27/442 (6.1%) 15/400 (3.8%) Previous PCI 83/442 (18.8%) 86/400 (21.5%) Previous CABG 1/442 (0.2%) 4/400 (1.0%) Previous stroke 15/442 (3.4%) 21/400 (5.3%) Renal Insufficiency 9/442 (2.0%) 13/400 (3.3%) Clinical presentation Unstable angina 149/442 (33.7%) 141/400 (35.3%) Non-ST elevation myocardial infarction 183/442 (41.4%) 156/400 (39.0%) ST elevation myocardial infarction 110/442 (24.9%) 103/400 (25.7%) KM plot for target lesion failure Conclusion The COMPARE-ABSORB trial showed no difference in the primary endpoint at one year for the ACS subgroup. The signal for increased thrombosis remained, even with the optimized implantation protocol Acknowledgement/Funding Maasstad Hospital, Rotterdam, the Netherlands

Aim There are inconsistent data on the sex-related differences in clinical outcomes after percutaneous transluminal angioplasty (PTA) in patients with peripheral artery disease (PAD). We aimed to investigate sex-related differences in clinical outcomes after PTA. Methods A total of 939 consecutive patients undergoing PTA were enrolled in two large volume centers. Patients were stratified by gender. Baseline characteristics, procedural and long-term clinical outcomes were compared between women and men. Results Women represented 37.4% of the study population. Women, compared to men, had more often hypertension (92% vs 86%, p=0.001) and diabetes (54% vs 46%, p=0.02). However, men presented more often with chronic obstructive pulmonary disease (14.8% vs 6.8%, p=0.0003), coronary artery disease (45.4% vs 32.7%, p=0.0001), smoking (60.4% vs 45%, p=0.007) and previous PTA (25% vs 17%, p=0.005). There were no differences in 120-month all-cause mortality between groups (women vs. men: 29% vs. 21%, p=0.6). Men were at higher risk of re-PTA at 5-year follow-up (40% vs. 49%; p=0.03). Moreover, male sex was an independent predictor of re-PTA (age-adjusted odds ratio (OR) (95% CI): 1.276 (1.015–1.614), p=0.03). In multivariable Cox regression analysis, a superficial femoral artery chronic total occlusion (SFA-CTO) (hazard ratio [HR]) (95% confidence interval [CI]): 1.68 (1.12–2.5), body mass index (BMI) (hazard ratio (HR)) (95% CI): 0.93 (0.87–0.99), baseline creatinine level hazard ratio (HR)) (95% CI): 0.95 (0.88–0.99) were identified as independent factors of re-PTA in women. Figure 1. Months to re-PTA for grouping variable male. Conclusion Male sex was identified as an independent predictor of re-PTA. SFA-CTO, BMI and baseline creatinine level were associated with re-PTA in women.

Background Three-dimensional (3D) echocardiographic data acquired from transesophageal (TEE) window are commonly used in planning and during percutaneous structural cardiac interventions (PSCI). Purpose We hypothesized that innovative, interactive mixed reality display can be integrated with procedural PSCI workflow to improve perception and interpretation of 3D data representing cardiac anatomy. Methods 3D TEE datasets were acquired before, during and after the completion of PSCI in 8 patients (occluders: 2 atrial appendage, 2 patent foramen ovale and 3 atrial septal implantations and percutaneous mitral commissurotomy). 30 Carthesian DICOM files were used to test the feasibility of mixed reality with commercially available head-mounted device (overlying hologram of 3D TEE data onto real-world view) as display for the interventional or imaging operator. Dedicated software was used for files conversion and 3D rendering of data to display device (in 1 case real-time Wi-Fi streaming from echocardiograph) and spatial manipulation of hologram during PSCI. Custom viewer was used to perform volume rendering and adjustment (cropping, transparency and shading control). Results Pre- and intraprocedural 3D TEE was performed in all 8 patients (5 women, age 40–83). Thirty selected 3DTEE datasets were successfully transferred and displayed in mixed reality head-mounted device as a holographic image overlying the real world view. The analysis was performed both before and during the procedure and compared with flatscreen 2-D display of the echocardiograph. In one case, real-time data transfer was successfully implemented during mitral balloon commissurotomy. The quality of visualization was judged as good without diagnostic content loss in all (100%) datasets. Both target structures and additional anatomical details were clearly presented including fenestrations of atrial septal defect, prominent Eustachian valve and earlier cardiac implants. Volume rendered views were touchlessly manipulated and displayed with a selection of intensity windows, transfer functions, and filters. Detail display was judged comparable to current 2-D volume-rendering on commercial workstations and touchless user interface - comfortable for optimization of views during PSCI. Conclusions Mixed reality display using a commercially available head-mounted device can be successfully integrated with preparation and execution of PSCI. The benefits of this solution include touchless image control and unobstructed real world viewing facilitating intraprocedural use, thus showing superiority over virtual or enhanced reality solutions. Expected progress includes integration of color flow data and optimization of real-time streaming option.

Background According to epidemiological studies, increased air pollution has negative impact on the cardiovascular system. However, the extent of the air pollution's impact on the frequency of the occurrence of specific subtypes of coronary artery diseases (CAD) has not yet been established with absolute certainty. Purpose The aim of the study was to assess the relationship between increased air pollution expressed as particulate air matter (PM10) concentrations and the occurrence of acute coronary syndromes (ACSs). Methods Based on the data published by the Chief Inspectorate for Environmental Protection, we selected six cities (six catheter laboratories [cath labs]) with low pollution according to PM10 (“non-polluted”) and five cities (six cath labs) with the highest pollution (“polluted”). These locations served as a basis for the determination of 24/7 cath labs and the frequency of percutaneous coronary interventions in patients (PCIs) with subsequent types of CAD with special outlook on the ACSs. The current study accounted 10,239 patients in the polluted area and 5,648 patients from the non-polluted region treated with PCI and included patients with stable angina and ACSs. Analysing the period of 365 days, the number of patients undergoing angioplasty in monitored cath labs and the mean daily concentration of PM10 in all selected cities were calculated for each day. In order to better visualise air pollution trends and the frequency of performing PCI in patients with ACS, we have created new time intervals for weeks. Additionally, due to the difference in pollution levels, the analysed period was divided into winter (13 weeks) and non-winter weeks (39 weeks). Results The annual average concentration of PM10 amounts to 50.95 μg/m3 in polluted cities and 26.62 μg/m3 in non-polluted ones, which was significantly different (p Figure 1. Biplot chart according to the extent of pollution expressed as PM10 and sample size for selected Cathlabs. Conclusions The study shows that the increase in air pollution expressed as PM10 concentration and winter time influences the frequency of ACS related PCIs.

Background: A novel bioresorbable scaffold, the sirolimus-eluting Fantom, incorporates a radiopaque polymer, struts with a thickness of 125 µm, and a crossing profile of 1.35 mm. The purpose of this study was to evaluate the 9-month angiographic and 12-month clinical outcomes of the FANTOM scaffold in a larger patient population. Methods and Results: The FANTOM II study (Safety & Performance Study of the Fantom Sirolimus-Eluting Bioresorbable Coronary Scaffold – First Report on Initial 24 Month Outcomes) was a prospective, multicenter trial which enrolled 240 patients with single de novo coronary stenosis with reference vessel diameter 2.5 to 3.5 mm diameter and lesion length ≤20 mm. Major adverse cardiac events through 12-month follow-up were assessed. Angiographic follow-up was performed in consecutive patient cohorts at 6 months (n=117) and 9 months (n=123). Acute delivery success, acute technical success, acute procedural success, and clinical procedural success rates as defined in the clinical protocol were 97.9% (235/240), 95.8% (230/240), 99.1% (228/230), and 99.6% (227/228), respectively. The mean in-stent late lumen loss at 6 months and 9 months were 0.25±0.40 mm and 0.33±0.36 mm, respectively, and in-segment binary restenosis occurred in 2.0% and 7.6% of patients, respectively. Major adverse cardiac events and target lesion failure through 12 months occurred in 4.2% of 240 patients; scaffold thrombosis developed in only one patient (0.4%). Conclusions: The Fantom sirolimus-eluting bioresorbable coronary scaffold demonstrated favorable safety and effectiveness performance at 12-month follow-up. Longer-term follow-up is ongoing to examine the late outcomes with this novel device. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02539966.

Background. In recent years, pathophysiology of aortic stenosis (AS) has been considered as a possibly active inflammatory process, but its determinants remain unclear. Calcium tissue deposition observed in dilaysis patients have been linked to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is thus suspected to play a role in development of aortic stenosis. Purpose. To assess correlation between Fetuin-A level and AS progression in a prospective cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC (clinicalTrial.gov_number_NCT00647088). Methods. A comprehensive clinical evaluation and Fetuin-A plasma level measurement was performed at baseline. AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification or AVC). Annual progression was calculated as [(final measurement - baseline measurement)/follow-up duration] for both MPG and AVC measurements. Results. We enrolled 296 patients with at least 1 year of follow-up. Mean age was 74±10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55±0.15 g/L. After a mean follow-up of 3.0±1.7 years, no correlation was found between AS progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC (r=0.014, p=0.82). This was also true when comparing patients with lower level of Fetuin-A (≤0.53 g/L, the median in our cohort) with patients with higher level(+3±5 mmHg/year (median 2, [0-5] vs +4±4 mmHg/year (median 2, [1-6]) p=0.06, and +205±290 AUC/year (median 122, [32-269]) vs +240±310 AUC/year (median 145, [50-313], p=0.24). This was true also after adjustment for baseline severity and valve antomy. Conclusions. In our prospective cohortot of AS patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS progression. Despite strong capacity to inhibit ectopic calcium deposition, Fetuin-A plasma level seems to have minor influence on AS progression.

Das akute Koronarsyndrom (ACS) wird entweder durch eine signifikante Verengung oder einen vollstandigen Verschluss einer Koronararterie verursacht. Post-mortem-Studien konnten zeigen, dass kritische Stenosen bzw. der Verschluss einer Arterie bei Patienten mit ACS, die angiographische „culprit lesion“ (CL), vor allem aus frischem Thrombusmaterial bestehen; die Plaque-Ruptur – die eigentliche Ursache des Thrombenmaterials (wahre CL, „culprit of the CL“) – ist proximal oder distal der Lasion zu finden. Die Koronarangiographie reicht demzufolge als diagnostisches Werkzeug zur sicheren Identifikation und Untersuchung der wahren CL (Lange, Thrombusanteil, Durchmesser, Lokalisierung der Plaque-Ruptur, Identifikation von vulnerablen Plaque) nicht mehr aus. Der intravaskulare Ultraschall (IVUS) erlaubt es einem interventionellen Kardiologen, die Gefaswand und den atherosklerotischen Prozess in vivo zu sehen. Intravaskularer „Virtual-histology“-Ultraschall stellt 4 Farben dar: hellgrun („fibrofatty tissue“), dunkelgrun („fibrotic tissue“), weis („calcified tissue“) und rot („necrotic core“). Die optische Koharenztomographie ist eine neue Art der intravaskularen Bildgebung; sie erlaubt, ahnlich wie der IVUS, jedoch praziser die In-vivo-Vermessung der Koronararterien (Durchmesser, Lange etc.) und die Bestimmung der CL (Thrombuslast, Plaque-Ruptur, Lange) sowie die Optimierung nach primarer perkutaner Koronarintervention (PPCI).

The Fantom bioresorbable scaffold (BRS) is radiopaque with a strut thickness of 125 um. Six and nine months after implantation tissue coverage was almost complete and malapposition was effectively reduced. The current study aimed to evaluate late healing patterns 24 months after implantation

Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model. Further, either in vivo or in vitro Mn supplementation reverses the urea-cycle pathology by restoring arginase activity. We show that Arginase 2 (ARG2) is the arginase enzyme present in these mouse brain models, with ARG2 protein levels directly increased by Mn exposure. ARG2 protein is not reduced in the prodromal stage, though enzyme activity is reduced, indicating that altered Mn bioavailability as a cofactor leads to the deficient enzymatic activity. These data support a hypothesis that mutant HTT leads to a selective deficiency of neuronal Mn at an early disease stage, contributing to HD striatal urea-cycle pathophysiology through an effect on arginase activity.

No abstract available - Guidelines

Background— The relationship between white blood cell count (WBCc) and mortality in patients with ST-segment–elevation acute myocardial infarction treated with percutaneous coronary intervention is poorly understood. Furthermore, whether there is a relationship between WBCc and risk of noncardiac mortality and bleeding after percutaneous coronary intervention is unknown. Methods and Results— The baseline WBCc was available in 3193 of 3345 patients (95.5%) who underwent percutaneous coronary intervention in the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial. In a propensity-adjusted multivariable analysis, WBCc was an independent predictor of 1-year cardiac mortality (hazard ratio, 1.15; 95% confidence interval, 1.09 to 1.22), noncardiac mortality (hazard ratio, 1.19; 95% confidence interval, 1.10 to 1.29), and major bleeding (hazard ratio, 1.08; 95% confidence interval, 1.04 to 1.12). After adjustment for baseline creatinine phosphokinase levels and left ventricular ejection fraction, WBCc remained an independent predictor of 1-year all-cause mortality and cardiac mortality. In patients matched for baseline creatinine phosphokinase levels at hospital admission, the median peak creatinine phosphokinase level was significantly higher in patients with high WBCc (>11 000 per 1 mm 3 ) compared with low WBCc (1851 U/L [range, 880-3307 U/L] versus 1241 U/L [range, 540 to 2,78], respectively; P Conclusions— In patients with ST-segment–elevation acute myocardial infarction undergoing percutaneous coronary intervention, elevated baseline WBCc is an independent predictor of infarct size, as assessed by peak creatinine phosphokinase level, and of 1-year cardiac mortality, noncardiac mortality, and major bleeding. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov . Unique identifier: NCT00433966.

The article presents basic reasons for plastic degradation of track links in working machine undercarriage. Besides the problems related to the loading of links with bending moment caused by passing of a machine (undercarriage) through trajectory curvatures, the important issue is the internal structure of the L35GSM cast steel, which conditions its usefulness as a material for track links. This issue is being discussed in the following publication.