Three new species of arbuscular mycorrhizal fungi (Glomeromycota) and Acaulospora gedanensis revised.

Studies of the morphology and the 45S nuc rDNA phylogeny of three potentially undescribed arbuscular mycorrhizal fungi (phylum Glomeromycota) grown in cultures showed that one of these fungi is a new species of the genus Diversispora in the family Diversisporaceae; the other two fungi are new Scutellospora species in Scutellosporaceae. Diversispora vistulana sp. nov. came from maritime sand dunes of the Vistula Spit in northern Poland, and S. graeca sp. nov. and S. intraundulata sp. nov. originally inhabited the Mediterranean dunes of the Peloponnese Peninsula, Greece. In addition, the morphological description of spores of Acaulospora gedanensis, originally described in 1988, was emended based on newly found specimens, and the so far unknown phylogeny of this species was determined. The phylogenetic analyses of 45S sequences placed this species among Acaulospora species with atypical phenotypic and histochemical features of components of the two inner germinal walls.

Cangrelor - Expanding therapeutic options in patients with acute coronary syndrome.

Cangrelor is the only intravenous P2Y12 receptor antagonist. It is an adenosine triphosphate analog that selectively, directly, and reversibly binds to the platelet P2Y12 receptors exerting its antiaggregatory effect. Cangrelor is characterized by linear, dose-dependent pharmacokinetics and rapid onset of action providing potent platelet inhibition exceeding 90%. Cangrelor is rapidly metabolized by endothelial endonucleotidase; thus, its half-life is 2.9 to 5.5 min, and its antiplatelet effect subsides within 60 to 90 min. Data originating from three pivotal cangrelor trials (CHAMPION PLATFORM, CHAMPION PCI, and CHAMPION PHOENIX) indicate that cangrelor reduces the risk of periprocedural thrombotic complications during percutaneous coronary intervention at the expense of mild bleedings. Its unique pharmacological properties allow it to overcome the limitations of oral P2Y12 receptor inhibitors, mainly related to the delayed and decreased bioavailability and antiplatelet effect of these agents, which are often observed in the setting of acute coronary syndrome. Subgroups of patients who could theoretically benefit the most from cangrelor include those in whom pharmacokinetics and pharmacodynamics of oral P2Y12 receptor antagonists are most disturbed, namely patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock. Cangrelor could also be useful if bridging is required in patients undergoing surgery. According to the current guidelines cangrelor may be considered in P2Y12 receptor inhibitor-naïve patients undergoing percutaneous coronary intervention in both acute and stable settings.

Pretreatment with P2Y12 Receptor Inhibitors in Acute Coronary Syndromes-Is the Current Standpoint of ESC Experts Sufficiently Supported?

Excessive platelet reactivity plays a pivotal role in the pathogenesis of acute myocardial infarction. Today, the vast majority of patients presenting with acute coronary syndromes qualify for invasive treatment strategy and thus require fast and efficient platelet inhibition. Since 2008, in cases of ST-elevation myocardial infarction, the European Society of Cardiology guidelines have recommended pretreatment with a P2Y12 inhibitor. This approach has become the standard of care in the majority of centers worldwide. Nevertheless, the latest guidelines for the management of patients presenting with acute coronary syndrome without persisting ST-elevation preclude routine pretreatment with the P2Y12 receptor inhibitor. Those who oppose pretreatment support their stance with trials failing to prove the benefits of this strategy at the cost of an increased risk of major bleeding, especially in individuals inappropriately diagnosed with an acute coronary syndrome, thus having no indication for platelet inhibition. However, adequate platelet inhibition requires even up to several hours after application of a loading dose of P2Y12 receptor inhibitors. Omission of data from pharmacokinetic and pharmacodynamic studies in the absence of data from clinical studies makes generalization of the pretreatment recommendations difficult to accept. We aimed to review the scientific evidence supporting the current recommendations regarding pretreatment with P2Y12 inhibitors.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

Inhibitors of sodium-glucose transport protein 2: A new multidirectional therapeutic option for heart failure patients.

Several mechanisms have been suggested to explain positive cardiovascular effects observed in studies with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The reduction in glucose reabsorption in proximal tubuli induced by SGLT2 inhibitors increases urinary glucose and sodium excretion resulting in increased osmotic diuresis and consequently in decreased plasma volume, followed by reduced preload. In addition, the hemodynamic effects of SGLT2 inhibition were observed in both hyper and euglycemic patients. Due to the complex and multidirectional effects induced by SGLT2 inhibitors, this originally antidiabetic group of drugs has been successfully used to treat patients with heart failure as well as for subjects with chronic kidney disease. Moreover, their therapeutic potential seems to be even broader than the indications studied to date.

Long-term outcomes following drug-eluting balloon or thin-strut drug-eluting stents for treatment of in-stent restenosis stratified by duration of dual antiplatelet therapy (DEB-Dragon Registry).

Introduction: Data regarding the duration of dual antiplatelet therapy (DAPT) in patients with drug-eluting stent restenosis (DES-ISR) treated with percutaneous coronary intervention (PCI) and drug-eluting balloons (DEB) or DES are not unambiguous. Aim: To evaluate the relationship between long-term outcomes and the length of DAPT in patients treated with PCI due to DES-ISR with DEB or DES. Material and methods: Overall, a total of 1,367 consecutive patients with DES-ISR, who underwent PCI with DEB or DES between 2008 and 2019 entered the study. The mean length of the follow-up was 1,298.7 ±794 days. We assessed study endpoints according to the duration of DAPT (≤ 3 vs. > 3 and ≤ 6 vs. > 6 months) before and after propensity score matching (PSM): stroke, target lesion revascularisation (TLR), target vessel revascularisation (TVR), myocardial infarction (MI), death and device oriented composite endpoints (DOCE). Kaplan-Meier estimates were created to differentiate long-term outcomes. Results: Pairwise contrast analysis considering type of PCI (DES vs. DEB) and duration of DAPT (≤ 6 vs. > 6 months) before PSM revealed superiority of DES + DAPT > 6 months vs. DEB + DAPT > 6 months for DOCE (p < 0.001), TVR (p = 0.02) and TLR (p = 0.01). Also, DES + DAPT ≤ 6 months was found to be superior compared to DEB + DAPT ≤ 6 months for DOCE (p < 0.001), TVR (p = 0.02) and TLR (p = 0.01). Kaplan-Meier estimate analysis confirmed that DAPT > 6 months is related to a higher stroke rate (p = 0.01) when compared to ≤ 6 months. Conclusions: Treatment with DAPT in patients with DES-ISR is related to better long-term outcomes in the case of PCI with DES than DEB. DAPT > 6 months is related to the greater rate of strokes, independently of the type of treatment (DES and DEB) than DAPT ≤ 6 months.

Long-term outcomes following drug-eluting balloons vs. thin-strut drug-eluting stents for treatment of recurrent restenosis in drug-eluting stents.

BACKGROUND: There is limited data on the optimal revascularization strategy in patients with recurrent in-stent restenosis (R-ISR). AIMS: To compare the long-term outcomes of patients treated with either a thin-strut drug-eluting stent (thin-DES) or a drug-eluting balloon (DEB) for R-ISR in a drug-eluting stent (DES). METHODS: A multicenter DEB-DRAGON registry was used to retrospectively identify patients with R-ISR who received either a thin-DES or a DEB. Propensity score matching was applied to adjust for baseline differences. The primary outcome was target lesion revascularization (TLR). RESULTS: Out of 311 patients (mean age, 67 years; 63% male) with R-ISR, 86 (27.7%) were treated with a thin-DES and 225 (72.3%) with a DEB. Median follow-up was 2.6 years. TLR occurred in 18 (20.9%) patients who received thin-DES and 61 (27.1%) patients treated with DEB (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.98; log-rank P = 0.04). The difference remained significant in a propensity score-matched cohort of 57 patients treated with thin-DES and 57 patients treated with a DEB (17.5 vs. 33.3%, respectively; HR, 0.38; 95% CI, 0.17-0.86; P = 0.01). The risks of device-oriented adverse cardiac events and all-cause mortality were similar after thin-DES or DEB in both unadjusted and propensity score-matched cohorts. In a multivariable Cox proportional hazard model, the treatment with a thin-DES was an independent predictor of a TLR-free survival (HR, 0.33; 95% CI 0.13-0.84; P = 0.02). CONCLUSIONS: In patients with R-ISR implantation of a thin-DES is associated with a lower risk of repeated revascularization compared with angioplasty with a DEB.

Three new species of arbuscular mycorrhizal fungi of the genus Diversispora from maritime dunes of Poland.

Three new species of arbuscular mycorrhizal fungi of the genus Diversispora (phylum Glomeromycota) were described based on their morphology and molecular phylogeny. The phylogeny was inferred from the analyses of the partial 45S rDNA sequences (18S-ITS-28S) and the largest subunit of RNA polymerase II (rpb1) gene. These species were associated in the field with plants colonizing maritime sand dunes of the Baltic Sea in Poland and formed mycorrhiza in single-species cultures.

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor - NARCOTIC trial.

BACKGROUND: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral coadministration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome 'the morphine effect'. METHODS: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at 9 pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. RESULTS: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. CONCLUSIONS: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile.

A new order, Entrophosporales, and three new Entrophospora species in Glomeromycota.

As a result of phylogenomic, phylogenetic, and morphological analyses of members of the genus Claroideoglomus, four potential new glomoid spore-producing species and Entrophospora infrequens, a new order, Entrophosporales, with one family, Entrophosporaceae (=Claroideoglomeraceae), was erected in the phylum Glomeromycota. The phylogenomic analyses recovered the Entrophosporales as sister to a clade formed by Diversisporales and Glomeraceae. The strongly conserved entrophosporoid morph of E. infrequens, provided with a newly designated epitype, was shown to represent a group of cryptic species with the potential to produce different glomoid morphs. Of the four potential new species, three enriched the Entrophosporales as new Entrophospora species, E. argentinensis, E. glacialis, and E. furrazolae, which originated from Argentina, Sweden, Oman, and Poland. The fourth fungus appeared to be a glomoid morph of the E. infrequens epitype. The physical association of the E. infrequens entrophosporoid and glomoid morphs was reported and illustrated here for the first time. The phylogenetic analyses, using nuc rDNA and rpb1 concatenated sequences, confirmed the previous conclusion that the genus Albahypha in the family Entrophosporaceae sensu Oehl et al. is an unsupported taxon. Finally, the descriptions of the Glomerales, Entrophosporaceae, and Entrophospora were emended and new nomenclatural combinations were introduced.

Long-Term Outcomes Following Drug-Eluting Balloons Versus Thin-Strut Drug-Eluting Stents for Treatment of In-Stent Restenosis (DEB-Dragon-Registry).

[Figure: see text].

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

New Glomeromycotan Taxa, Dominikia glomerocarpica sp. nov. and Epigeocarpum crypticum gen. nov. et sp. nov. From Brazil, and Silvaspora gen. nov. From New Caledonia.

Examination of fungal specimens collected in the Atlantic rain forest ecosystems of Northeast Brazil revealed many potentially new epigeous and semihypogeous glomerocarp-producing species of the phylum Glomeromycota. Among them were two fungi that formed unorganized epigeous glomerocarps with glomoid spores of almost identical morphology. The sole structure that distinguished the two fungi was the laminate layer 2 of their three-layered spore wall, which in spores of the second fungus crushed in PVLG-based mountants contracted and, consequently, transferred into a crown-like structure. Surprisingly, phylogenetic analyses of sequences of the 18S-ITS-28S nuc rDNA and the rpb1 gene indicated that these glomerocarps represent two strongly divergent undescribed species in the family Glomeraceae. The analyses placed the first in the genus Dominikia, and the second in a sister clade to the monospecific generic clade Kamienskia with Kamienskia bistrata. The first species was described here as Dominikia glomerocarpica sp. nov. Because D. glomerocarpica is the first glomerocarp-forming species in Dominikia, the generic description of this genus was emended. The very large phylogenetic distance and the fundamental morphological differences between the second species and K. bistrata suggested us to introduce a new genus, here named as Epigeocarpum gen. nov., and name the new species Epigeocarpum crypticum sp. nov. In addition, our analyses also focused on an arbuscular mycorrhizal fungus originally described as Rhizophagus neocaledonicus, later transferred to the genus Rhizoglomus. The analyses indicated that this species does not belong to any of these two genera but represents a new clade at the rank of genus in the Glomeraceae, here described as Silvaspora gen. nov.

ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial.

INTRODUCTION: The unfavourable influence of morphine on the pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect in patients with acute coronary syndrome (ACS) has been previously shown. Replacing morphine with methoxyflurane, a potent, non-opioid analgesic agent, that does not weaken or delay the effect of antiplatelet agents may improve the clinical efficacy of treatment of patients with ACS. METHODS: The ANEMON-SIRIO 3 study was designed as a multicentre, open-label, phase II, randomised clinical trial aimed to test the analgesic efficacy and safety of methoxyflurane in patients with ACS. The study population will comprise patients with ST-elevation myocardial infarction or non-ST-elevation ACS admitted to the study centres with typical chest pain requiring analgesic treatment. Before percutaneous coronary intervention (PCI) for the patients with index ACS will be randomly assigned in 1:1 ratio to receive methoxyflurane administered by inhalation, or to obtain morphine administered intravenously. Analgesic treatment will be followed by 300 mg loading dose of aspirin and 180 mg loading dose of ticagrelor. Patients will be assessed with regard to pain intensity according to the Numeric Pain Rating Scale at baseline, 3 min after study drug administration and immediately after PCI. Moreover, patients will be actively monitored with regard to the occurrence of side effects of evaluated therapies, as well as adverse events that may be related to insufficient platelet inhibition (no-reflow phenomenon assessed immediately after PCI, administration of GPIIb/IIIa inhibitors during PCI, acute stent thrombosis). ETHICS AND DISSEMINATION: The study will be conducted in six Polish clinical centres from the beginning of in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov, NCT04476173.

Preparation and Characterization of Acrylic Pressure-Sensitive Adhesives Crosslinked with UV Radiation-Influence of Monomer Composition on Adhesive Properties.

In this study, syntheses of acrylate copolymers were performed based on the monomers butyl acrylate (BA), 2-ethylhexyl acrylate (2-EHA), and acrylic acid (AA) and the second-type unsaturated photoinitiator 4-acryloyloxybenzophenone (ABP). The structure of the obtained copolymers was confirmed via FT-IR spectroscopic analysis, and the viscosity and the content of non-volatile substances were determined. The adhesive films were then coated and cross-linked using ultraviolet radiation in the UV-C range at various doses (5-50 mJ/cm2). Due to the dependence of the self-adhesive properties of the adhesive layer on the basis weight, various basis weights of the layer in the range of 30-120 g/m2 were tested. Finally, the self-adhesive properties were assessed: tack, peel adhesion, shear strength (cohesion) at 20 °C and 70 °C, as well as the SAFT test and shrinkage. The aim of the study was to determine the effect of the type of monomer used, the dose of ultraviolet radiation, and the basis weight on the self-adhesive and usable properties of the obtained self-adhesive tapes.

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.