Impact of the Coexisting Coronary Artery Disease on Five-Year Outcomes in Lower Extremity Artery Disease Patients Without Chronic Limb-Threatening Ischemia.

Coronary artery disease (CAD) is often noted in patients with lower-extremity artery disease (LEAD). However, the effects of CAD on patients with LEAD have not been clearly investigated. In this study, to investigate the effect of CAD on patients with LEAD without chronic limb-threatening ischemia (CLTI), we compared the five-year clinical outcomes of patients with and without CAD. Between 2014 and 2017, 246 patients with symptomatic LEAD without CLTI underwent endovascular treatment. Patients with a history of CAD revascularization or CAD defined by CAD studies were divided into CAD groups, and others were non-CAD groups. After excluding ineligible patients, propensity matching produced 40 patients in each group, and clinical outcomes were compared between the groups. Using five years of Kaplan-Meier analysis between the CAD and non-CAD groups, no significant differences were observed in survival (90.0% vs 92.5%, p=0.693), freedom from cardiovascular events (42.5% vs 57.5%, p=0.110), freedom from LEAD revascularization (67.5% vs 67.5%, p=0.940), and freedom from CLTI (100% vs. 95.0%, p=0.148). However, significant differences were observed in freedom from CAD revascularization (67.5% vs 97.5%, p<0.001) and freedom from symptomatic CAD (85.0% vs 97.5%, p=0.048). Our results suggest that in patients with LEAD without CLTI, CAD caused increased CAD revascularization and symptomatic CAD. However, CAD did not affect survival, cardiovascular events, LEAD revascularization, or CLTI in such patients. When CAD was observed in patients with LEAD without CLTI, more frequent follow-up of CAD may improve the long-term clinical outcomes of such patients.

Optical frequency domain imaging of the scoring balloon elements shift.

Here, we report a case of endovascular treatment in which optical frequency domain imaging evaluated the scoring balloon elements shift when three inflations without shaft rotation performed with a scoring balloon.

A novel initial wiring technique for chronic total occlusion of the superficial femoral artery using the structural features of a polymer jacket guidewire.

BACKGROUND: To evaluate the efficacy of the GLadIus MG drilLINg technique (GLIMGLIN), a novel initial wiring technique using the Gladius MG™ structural features, for crossing the superficial femoral artery (SFA) with chronic total occlusion (CTO). METHODS: This retrospective, single-center study enrolled 27 symptomatic patients (mean age 77.4 ± 8.5 years; 20 men) with de novo SFA CTO (mean CTO length 16.1 ± 8.9 cm) who underwent GLIMGLIN as the initial wiring between January 2020 and December 2021. The success of GLIMGLIN was defined when the wire crossing was completed using a Gladius MG™ and a microcatheter without any additional devices and techniques. RESULTS: The success rate of GLIMGLIN was 48.1%. Intravascular ultrasound findings showed complete true lumen passage in the GLIMGLIN success group. Compared to the failure group, the proximal (6.3 ± 0.8 vs. 5.5 ± 0.9 mm, p = 0.02) and distal (5.9 ± 0.5 vs. 5.4 ± 0.6 mm, p = 0.02) reference vessel diameters were significantly larger, and the rate of calcium angle > 180° was significantly lower (30.8 vs. 71.4%, p = 0.04) in the success group. No significant difference was shown in the CTO length between two groups. Total wiring time, total procedure time, and fluoroscopic time were significantly shorter in the success group. CONCLUSIONS: GLIMGLIN may enable operators to perform CTO wiring easily and efficiently in selected cases.

Space Exposure of Amino Acids and Their Precursors during the Tanpopo Mission.

Amino acids have been detected in extraterrestrial bodies such as carbonaceous chondrites (CCs), which suggests that extraterrestrial organics could be the source of the first life on Earth, and interplanetary dust particles (IDPs) or micrometeorites (MMs) are promising carriers of extraterrestrial organic carbon. Some amino acids found in CCs are amino acid precursors, but these have not been well characterized. The Tanpopo mission was conducted in Earth orbit from 2015 to 2019, and the stability of glycine (Gly), hydantoin (Hyd), isovaline (Ival), 5-ethyl-5-methylhydantoin (EMHyd), and complex organics formed by proton irradiation from CO, NH3, and H2O (CAW) in space were analyzed by high-performance liquid chromatography and/or gas chromatography/mass spectrometry. The target substances showed a logarithmic decomposition over 1-3 years upon space exposure. Recoveries of Gly and CAW were higher than those of Hyd, Ival, and EMHyd. Ground simulation experiments showed different results: Hyd was more stable than Gly. Solar ultraviolet light was fatal to all organics, and they required protection when carried by IDPs/MMs. Thus, complex amino acid precursors (such as CAW) were possibly more robust than simple precursors during transportation to primitive Earth. The Tanpopo 2 mission is currently being conducted to expose organics to more probable space conditions.

Very Short Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients Who Underwent Complex Percutaneous Coronary Intervention: Insight From the STOPDAPT-2 Trial.

BACKGROUND: Safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) is uncertain in patients undergoing complex percutaneous coronary intervention (PCI). METHODS: We conducted a post hoc subgroup analysis based on the complexity of PCI in the STOPDAPT-2 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-2), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after cobalt-chromium everolimus-eluting stent implantation. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents, >60 mm total stent lengths, and target of chronic total occlusion. The primary end point was the composite of cardiovascular (cardiovascular death/myocardial infarction/definite stent thrombosis/stroke) and bleeding (TIMI [Thrombolysis in Myocardial Infarction] major/minor) end points. The major secondary end points were the cardiovascular and bleeding end points. RESULTS: Among the 3009 study patients, there were 509 patients (16.9%) with complex PCI (1-month DAPT: N=245, and 12-month DAPT: N=264) and 2500 patients (83.1%) without complex PCI (1-month DAPT: N=1255, and 12-month DAPT: N=1245). There were no significant interactions between the complexity of PCI and the effects of 1-month DAPT versus 12-month DAPT on the primary end point (complex PCI: 1.67% versus 5.32%, hazard ratio, 0.30 [95% CI, 0.10­0.92], P=0.04, and noncomplex PCI: 2.50% versus 3.35%, hazard ratio, 0.75 [95% CI, 0.47­1.20], P=0.23; Pinteraction=0.14), and on the major secondary cardiovascular end point (complex PCI: 1.67% versus 3.04%, hazard ratio, 0.54 [95% CI, 0.16­1.79], P=0.31, and noncomplex PCI: 2.02% versus 2.39%, hazard ratio, 0.86 [95% CI, 0.50­1.47], P=0.58; Pinteraction=0.49). The cumulative 1-year incidence of the major secondary bleeding end point was significantly lower in the 1-month DAPT group than in the 12-month DAPT group regardless of the complexity of PCI (complex PCI: 0% versus 2.29%, log-rank P=0.02, and noncomplex PCI: 0.48% versus 1.38%, log-rank P=0.02). CONCLUSIONS: The effects of clopidogrel monotherapy after 1-month DAPT relative to 12-month DAPT for the primary and major secondary end points were comparable in complex PCI and noncomplex PCI without significant interactions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02619760.

Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2.

The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy might be promising after percutaneous coronary intervention (PCI). However, CYP2C19 loss-of-function (LOF) alleles have been reported to diminish the effect of clopidogrel, and clopidogrel monotherapy has a concern about the increased ischemic risk for patients with such alleles. STOPDAPT-2 is the multicenter prospective open-label, but adjudicator-blinded randomized control study comparing 1-month DAPT followed by clopidogrel monotherapy with the standard 12-month DAPT after PCI with cobalt-chromium everolimus-eluting stents. Among the participants of STOPDAPT-2, selected patients participated in a substudy of the CYP2C19 gene test. Patients with two CYP2C19*2 or *3 alleles were defined as the poor metabolizer (PM), one allele as the intermediate metabolizer (IM), and no allele as the extensive metabolizer (EM). The primary endpoint was the composite of cardiovascular and bleeding events, as defined in STOPDAPT-2. Among 750 (24.9%) patients with known CYP2C19 genotypes, 129 (17.2%) were PM, 367 (49.0%) were IM, and 254 (33.9%) were EM. The hazard ratios of 1-month DAPT relative to 12-month DAPT for the primary endpoint in PM, IM, and EM strata were 0.66 (95% CI 0.11-3.94), 1.94 (95% CI 0.60-6.31), and 0.21 (95% CI 0.02-1.78), respectively (P interaction = 0.17), and those for cardiovascular composite endpoint were 1.00 (95% CI 0.14-7.10), 6.10 (95% CI 0.75-49.55), and 0.26 (95% CI 0.03-2.34), respectively (P interaction = 0.12). In conclusion, for the selected patients in STOPDAPT-2 trial, CYP2C19 LOF alleles had no significant, consistent interaction with the effect of 1-month DAPT relative to 12-month DAPT for clinical outcomes, although the study was overtly underpowered. TRIAL REGISTRY: STOPDAPT-2 ClinicalTrials.gov number, NCT02619760.

Alteration and Stability of Complex Macromolecular Amino Acid Precursors in Hydrothermal Environments.

The early Solar System comprised a broad area of abiotically created organic compounds, including interstellar organics which were integrated into planetesimals and parent bodies of meteorites, and eventually delivered to the early Earth. In this study, we simulated interstellar complex organic compounds synthesized by proton irradiation of a gas mixture of CO, NH3, and H2O, which are known to release amino acids after acid hydrolysis on the basis of Kobayashi et al. (1999) who reported that at the first stage of chemical evolution, the main compounds formed abiotically are complex organic compounds with high molecular weights. We examined their possible hydrothermal alteration and stabilities as amino acid precursors under high temperature and pressure conditions simulating parent bodies of meteorites by using an autoclave. We reported that all samples treated at 200-300 °C predominantly released glycine and alanine, followed by α-aminobutyric acid, and serine. After heating, amino acid concentrations decreased in general; however, the recovery ratios of γ-aminobutyric acid increased with temperature. The interstellar complex organic analog could maintain as amino acid precursors after being treated at high temperature (200-300 °C) and pressure (8-14 MPa). However, the molecular structures were altered during heating to form organic compounds that are more stable and can survive in elevated hydrothermal conditions.

Usefulness of the "Non-Slip Element" Percutaneous Transluminal Angioplasty Balloon in the Treatment of Femoropopliteal Arterial Lesions.

Purpose: To evaluate a new scoring balloon, the non-slip element (NSE) percutaneous transluminal angioplasty (PTA) balloon, in the treatment of femoropopliteal lesions by comparing angiographic dissection patterns to those of a conventional balloon. Methods: This retrospective, single-center study included 71 symptomatic patients (mean age 77.4±8.8 years; 33 men) with de novo femoropopliteal lesions <20 cm long treated with balloon angioplasty between January 2017 and May 2018. Thirty-four patients were treated with 3 inflations of an NSE balloon and 37 patients were treated with a conventional balloon. Results: Severe dissections were fewer (8.8% vs 29.7%, p=0.027) and the total dissection length was shorter (11.5±12.8 vs 35.7±24.1 mm, p=0.027) in the NSE group. The bailout stenting rate was also lower in the NSE group (17.6% vs 40.5%, p=0.035). There were no significant differences between the groups regarding lesion length (70.3±50.4 vs 77.8±56.6 mm, p=0.28), inflation time (294±162 vs 353±179 seconds, p=0.08), or inflation pressure (10.6±5.0 vs 11.3±5.3 atm, p=0.31). Conclusion: Three NSE balloon inflations may reduce severe dissections induced by balloon angioplasty in femoropopliteal lesions.

Protrusion of a loop-shaped 0.035-inch wire without the fracture of the self-expanding nitinol stent: A case report and experimental study.

We report a case of a loop-shaped 0.035-inch wire protruding through self-expanding nitinol stent struts. Our in vitro experiment suggests that, even if there are no stent fractures, the loop-shaped 0.035-inch wire has a potential to protrude through the struts of the self-expanding nitinol stents.

Survivability and abiotic reactions of selected amino acids in different hydrothermal system simulators.

We tested the stability and reaction of several amino acids using hydrothermal system simulators: an autoclave and two kinds of flow reactors at 200-250 °C. This study generally showed that there is a variation in the individual amino acids survivability in the simulators. This is mainly attributed to the following factors; heat time, cold quenching exposure, metal ions and also silica. We observed that, in a rapid heating flow reactor, high aggregation and/or condensation of amino acids could occur even during a heat exposure of 2 min. We also monitored their stability in a reflow-type of simulator for 120 min at 20 min intervals. The non-hydrolyzed and hydrolyzed samples for this system showed a similar degradation only in the absence of metal ions.

The use of ascorbate as an oxidation inhibitor in prebiotic amino acid synthesis: a cautionary note.

It is generally thought that the terrestrial atmosphere at the time of the origin of life was CO(2)-rich and that organic compounds such as amino acids would not have been efficiently formed abiotically under such conditions. It has been pointed out, however, that the previously reported low yields of amino acids may have been partially due to oxidation by nitrite/nitrate during acid hydrolysis. Specifically, the yield of amino acids was found to have increased significantly (by a factor of several hundred) after acid hydrolysis with ascorbic acid as an oxidation inhibitor. However, it has not been shown that CO(2) was the carbon source for the formation of the amino acids detected after acid hydrolysis with ascorbic acid. We therefore reinvestigated the prebiotic synthesis of amino acids in a CO(2)-rich atmosphere using an isotope labeling experiment. Herein, we report that ascorbic acid does not behave as an appropriate oxidation inhibitor, because it contributes amino acid contaminants as a consequence of its reactions with the nitrogen containing species and formic acid produced during the spark discharge experiment. Thus, amino acids are not efficiently formed from a CO(2)-rich atmosphere under the conditions studied.

Photostability of Iiovaline and its precursor 5-Ethyl-5- methylhydantoin exposed to simulated space radiations.

Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and γ-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5-methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under γ-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected.

Chirality emergence in thin solid films of amino acids by polarized light from synchrotron radiation and free electron laser.

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of "chiral impulse" as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds.

Emphysematous cystitis with venous bubbles.

An 86-year-old nondiabetic woman with an episode of transient ischemic attack two days earlier was referred to our hospital. She had a history of neurogenic bladder and chronic atrial fibrillation and had been anuric for two days. Bubbles were detected by echocardiography in the right atrium, right ventricle, and inferior vena cava. Computed tomography revealed gas accumulation in the wall and lumen of the bladder. She recovered after urinary drainage and antibiotic therapy, and bubbles were no longer detected. It was suspected that bacterial injury of the bladder wall and high intravesical pressure led gas to enter the venous system.

Detection of biosphere frontier by using phosphatase activity.

A wide variety of methods have been proposed to detect microbial activities, but most of them can be applied to limited categories of terrestrial organisms. We propose here to use phosphatase activity, which seems to be an essential catalytic activity for all the terrestrial organisms, and possibly for extraterrestrial organisms. We determined phosphatase activity in core samples, chimney samples, and sea water samples obtained in submarine hydrothermal systems located at Suiyo Seamount, Izu-Bonin Arc, and South Mariana. It was shown that phosphatase activity is one of possible biomarkers for extant life.

Formation and stability of complex organic compounds in space environments.

Complex organic compounds have been found in extraterrestrial bodies such as meteorites and comets. We confirmed the formation of complex organic compounds that contained amino acid precursors from a mixture of carbon monoxide (or methanol), ammonia and water by radiation or UV. Molecular weights of the complex organics were several thousands. Stability of the complex precursors was studied. When free amino acids were irradiated with gamma rays or synchrotron radiation, they easily decomposed. The complex precursors were, however, much more stable than free amino acid against irradiation. We propose to examine the formation and alteration of amino acid precursors in space by using exposed facility of ISS.

Formation of organic compounds from simulated Titan atmosphere: perspectives of the Cassini mission.

Gas mixtures of methane and nitrogen were subjected to proton irradiation (PI), gamma irradiation (GI), UV irradiation (UV) or spark discharges (SD), and the products were analyzed to compare possible energy sources for synthesis of organics in Titan. SD mainly gave unsaturated hydrocarbons, while PI gave saturated hydrocarbons. N-containing organics were detected in PI, GI and SD, but not in UV. The formers yielded amino acids after acid-hydrolysis of solid phase products (tholin). Comparison of the present results with those by Cassini-Huygens [correction of Heygens] mission will make it possible to prove major energy sources for organic synthesis in Titan atmosphere.

Pyrolysis experiment of simulated exogenous complex organics synthesized from the gas mixtures of CO, NH3, and H2O by 3 MeV proton irradiation.

High molecular weight organic matter synthesized from mixtures of carbon monoxide, ammonia and water gases similar to those found in the interstellar medium were irradiated with a 3 MeV proton beam and analyzed by Curie point pyrolysis with detection by gas chromatograph and mass spectrometer (Pyr-GC-MS). A wide variety of organic compounds, not only a number of amide compounds, but also heterocyclic and polycyclic aromatic hydrocarbons (PAHs), were detected among the products of the pyrolysis. The present data shows that primary and primitive organic matter serving as precursors to bioorganic compounds such as amino acids, nucleic acid bases and sugar might have been formed in a gaseous mixture of similar composition to that of the interstellar dust environment.