Treatment of in-stent restenosis with ultrathin-strut versus thin-strut drug-eluting stents or drug-eluting balloons: a multicentre registry.

BACKGROUND: Limited data exist on ultrathin-strut drug-eluting stent (ultrathin DES) performance in DES in-stent restenosis (ISR). AIMS: We aimed to assess the efficacy and safety of ultrathin DES compared to thin-strut DES and drug-eluting balloons (DEB) for DES-ISR. METHODS: Patients from the DEB Dragon (ClinicalTrials.gov: NCT04415216) and ULTRA registries (ClinicalTrials.gov: NCT05205148) were divided into ultrathin DES, thin-strut DES, or DEB groups for DES-ISR treatment. Both propensity score matching (PSM) and inverse probability weighting (IPW) were considered to adjust the distribution of patients in each class. Cox regression was applied to the following main endpoints: device-oriented composite endpoints (DOCE; including cardiac death, target lesion revascularisation [TLR] and target vessel myocardial infarction), TLR and target vessel revascularisation (TVR). RESULTS: A total of 269, 541, and 557 patients received an ultrathin DES, thin-strut DES, and DEB, respectively. After 3 years of follow-up, in the IPW-adjusted overall cohort, ultrathin DES were associated with a significantly reduced risk of DOCE compared to DEBs (hazard ratio [HR] 0.353, 95% confidence interval [CI]: 0.194-0.642; p<0.001), as well as thin-strut DES (HR 0.645, 95% CI: 0.457-0.911; p=0.013). Compared to DEBs, ultrathin DES also reduced the risks of both TLR (HR 0.184, 95% CI: 0.081-0.417; p<0.001) and TVR (HR 0.188, 95% CI: 0.093-0.379; p<0.001), while thin-strut DES did not (TLR: HR 0.686, 95% CI: 0.407-1.157; p=0.157; TVR: HR 0.706, 95% CI: 0.453-1.101; p=0.124). For diffuse ISR patients, ultrathin DES reduced the risk of DOCE (HR 0.364, 95% CI: 0.188-0.705; p=0.003), as did thin-strut DES (HR 0.602, 95% CI: 0.367-0.987; p=0.044), while a reduction of TLR (HR 0.220, 95% CI: 0.091-0.531; p<0.001) and TVR (HR 0.241, 95% CI: 0.113-0.513; p<0.001) was achieved only by ultrathin DES. CONCLUSIONS: Ultrathin DES were associated with reduced DOCE, TLR and TVR risks in diffuse ISR compared to DEBs.

Drug-Eluting Balloons and Drug-Eluting Stents in Diabetic Patients Undergoing Percutaneous Coronary Intervention Due to Restenosis-DM-Dragon Registry.

Background: The rate of in-stent restenosis (ISR) is decreasing; however, it is still a challenge for contemporary invasive cardiologists. Therapeutic methods, including drug-eluting balloons (DEBs), intravascular lithotripsy, excimer laser coronary atherectomy, and imaging-guided percutaneous coronary intervention (PCI) with drug-eluting stents (DES), have been implemented. Patients with diabetes mellitus (DM) are burdened with a higher risk of ISR than the general population. Aims: DM-Dragon is aimed at evaluating the clinical outcomes of ISR treatment with DEBs vs. DES, focusing on patients with co-existing diabetes mellitus. Methods: The DM-Dragon registry is a retrospective study comprising data from nine high-volume PCI centers in Poland. A total of 1117 patients, of whom 473 individuals had DM and were treated with PCI due to ISR, were included. After propensity-score matching (PSM), 198 pairs were created for further analysis. The primary outcome of the study was target lesion revascularization (TLR). Results: In DM patients after PSM, TLR occurred in 21 (10.61%) vs. 20 (10.1%) in non-diabetic patients, p = 0.8690. Rates of target vessel revascularization (TVR), target vessel myocardial infarction, device-oriented composite endpoint (DOCE), and cardiac death did not differ significantly. Among diabetic patients, the risk of all-cause mortality was significantly lower in the DEB group (2.78% vs. 11.11%, HR 3.67 (95% confidence interval, CI) [1.01-13.3), p = 0.0483). Conclusions: PCI with DEBs is almost as effective as DES implantation in DM patients treated for ISR. In DM-Dragon, the rate of all-cause death was significantly lower in patients treated with DEBs. Further large-scale, randomized clinical trials would be needed to support these findings.

Long-Term Outcomes Following Sirolimus-Coated Balloon or Drug-Eluting Stents for Treatment of In-Stent Restenosis.

BACKGROUND: Evidence suggests that drug-coated balloons may benefit in-stent restenosis (ISR) treatment. However, the efficacy of new-generation sirolimus-coated balloon (SCB) compared with the latest generation drug-eluting stents (DESs) has not been studied in this setting. METHODS: All patients in the EASTBORNE (The All-Comers Sirolimus-Coated Balloon European Registry) and DEB-DRAGON (DEB vs Thin-DES in DES-ISR: Long Term Outcomes) registries undergoing percutaneous coronary intervention for DES-ISR were included in the study. The primary study end point was target lesion revascularization at 24 months. Secondary end points were major adverse cardiovascular events, all-cause death, myocardial infarction, and target vessel revascularization at 24 months. Our goal was to evaluate the efficacy and safety of SCB versus thin-struts DES in ISR at long-term follow-up. RESULTS: A total of 1545 patients with 1679 ISR lesions were included in the pooled analysis, of whom 621 (40.2%) patients with 621 lesions were treated with thin-strut DES and 924 (59.8%) patients with 1045 lesions were treated with SCB. The unmatched cohort showed no differences in the incidence of target lesion revascularization (10.8% versus 11.8%; P=0.568); however, there was a trend toward lower rates of myocardial infarction (7.4% versus 5.0%; P=0.062) and major adverse cardiovascular events (20.8% versus 17.1%; P=0.072) in the SCB group. After propensity score matching (n=335 patients per group), there were no significant differences in the rates of target lesion revascularization (11.6% versus 11.8%; P=0.329), target vessel revascularization (14.0% versus 13.1%; P=0.822), myocardial infarction (7.2% versus 4.5%; P=0.186), all-cause death (5.7% versus 4.2%; P=0.476), and major adverse cardiovascular event (21.5% versus 17.6%; P=0.242) between DES and SCB treatment. CONCLUSIONS: In patients with ISR, angioplasty with SCB compared with thin-struts DES is associated with comparable rates of target lesion revascularization, target vessel revascularization, myocardial infarction, all-cause death, and major adverse cardiovascular events at 2 years.

Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study.

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.

Long-term outcomes following paclitaxel-coated balloons versus thin-strut drug-eluting stents for treatment of in-stent restenosis in chronic coronary syndrome (CCS Dragon-Registry).

BACKGROUND: The long-term outcomes for patients with in-stent restenosis (ISR) presenting with chronic coronary syndrome (CCS) are not well studied. AIMS: We aimed to investigate the outcomes for patients with drug-eluting stents (DES)-ISR and CCS undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCB) or thin strut-DES. METHODS: A total of 846 consecutive patients from the Dragon-Registry with CCS and DES-ISR who underwent PCI with thin (strut thickness <100 µm) strut-DES (381 [45%]) or paclitaxel-DCB (465 [55%]) for DES-ISR were enrolled between February 2008 and October 2021. The median follow-up was 1006 (IQR 426-1770) days. The primary outcome was target lesion revascularization (TLR). Secondary outcomes were target vessel revascularization (TVR) and device-oriented composite endpoint (DOCE: cardiac death, TLR, or target vessel myocardial infarction [TV-MI]). RESULTS: Patients who received DES, compared with those who received DCB, had lower crude rates of TLR (hazard ratio [HR], 0.50 [95% CI, 0.34-0.74]; P <0.001), TVR (HR, 0.56 [95% CI, 0.39-0.86]; P <0.001), and DOCE (HR, 0.63 [95% CI, 0.45-0.88]; P = 0.007). The incidence of cardiac death and TV-MI were similar in both groups. After matching, the observed differences persisted in terms of TLR (HR, 0.54 [95% CI, 0.33-0.88]; P = 0.013), TVR (HR, 0.57 [95% CI, 0.41-0.80]; P = 0.009) and DOCE (HR, 0.65 [95% CI, 0.42-0.99]; P = 0.046) between the DES and DCB groups, respectively. CONCLUSIONS: In long-term follow-up of CCS patients undergoing PCI of ISR, the use of DES was associated with reduced rates of TLR, TVR, and DOCE compared with patients treated with DCB.

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.