Long-Term Follow-Up of Transthoracic Echocardiography-Guided Transcatheter Closure of Large Atrial Septal Defects (≥ 30 mm) Using the SHSMA Occluder.

Transcatheter closure of large atrial septal defects (ASDs) remains controversial. The aim of this study was to evaluate the feasibility and safety of transthoracic echocardiography (TTE)-guided transcatheter closure of large ASDs. Patients with large secundum ASDs (≥ 30 mm) who underwent device closure were retrospectively reviewed. TTE was performed to guide ASD occluder positioning and assess the immediate and long-term outcomes. A total of 60 patients (median age 43.5 years, range 15-78 years) were enrolled in the study. The median ASD size was 35 mm (range 30-42 mm). Mild to moderate pulmonary hypertension was observed in 36 patients (60%). Thirty-one patients (51.7%) had one short rim, and 18 patients (30.0%) had two deficient rims. Placement of the device was successful in 57 patients (95%), and the median device size was 42 mm (range 40-50 mm). Dislodgement of the device occurred in three patients with two deficient rims: a larger device was redeployed in one case, and two patients required surgical repair. During a median follow-up of 37 months (range 6-83 months), no residual shunts, erosion, or embolization were noted, and pulmonary hypertension resolved in 75% of the patients. Thus t vast majority (95%) of large ASDs can be successfully closed percutaneously using the Chinese-made Shanghai Shape Memory Alloy (SHSMA) occluder under TTE guidance. Long-term follow-up showed that transcatheter closure could become a safe and effective alternative to surgery in select large ASDs.

YNL134C from Saccharomyces cerevisiae encodes a novel protein with aldehyde reductase activity for detoxification of furfural derived from lignocellulosic biomass.

Furfural and 5-hydroxymethylfurfural (HMF) are the two main aldehyde compounds derived from pentoses and hexoses, respectively, during lignocellulosic biomass pretreatment. These two compounds inhibit microbial growth and interfere with subsequent alcohol fermentation. Saccharomyces cerevisiae has the in situ ability to detoxify furfural and HMF to the less toxic 2-furanmethanol (FM) and furan-2,5-dimethanol (FDM), respectively. Herein, we report that an uncharacterized gene, YNL134C, was highly up-regulated under furfural or HMF stress and Yap1p and Msn2/4p transcription factors likely controlled its up-regulated expression. Enzyme activity assays showed that YNL134C is an NADH-dependent aldehyde reductase, which plays a role in detoxification of furfural to FM. However, no NADH- or NADPH-dependent enzyme activity was observed for detoxification of HMF to FDM. This enzyme did not catalyse the reverse reaction of FM to furfural or FDM to HMF. Further studies showed that YNL134C is a broad-substrate aldehyde reductase, which can reduce multiple aldehydes to their corresponding alcohols. Although YNL134C is grouped into the quinone oxidoreductase family, no quinone reductase activity was observed using 1,2-naphthoquinone or 9,10-phenanthrenequinone as a substrate, and phylogenetic analysis indicates that it is genetically distant to quinone reductases. Proteins similar to YNL134C in sequence from S. cerevisiae and other microorganisms were phylogenetically analysed.

Alcohol dehydrogenases from Scheffersomyces stipitis involved in the detoxification of aldehyde inhibitors derived from lignocellulosic biomass conversion.

Aldehyde inhibitors such as furfural and 5-hydroxymethylfurfural (HMF) are generated from biomass pretreatment. Scheffersomyces stipitis is able to reduce furfural and HMF to less toxic furanmethanol and furan-2,5-dimethanol; however, the enzymes involved in the reductive reaction still remain unknown. In this study, transcription responses of two known and five putative alcohol dehydrogenase genes from S. stipitis were analyzed under furfural and HMF stress conditions. All the seven alcohol dehydrogenase genes were also cloned and overexpressed for their activity analyses. Our results indicate that transcriptions of SsADH4 and SsADH6 were highly induced under furfural and HMF stress conditions, and the proteins encoded by them exhibited NADH- and/or NADPH-dependent activities for furfural and HMF reduction, respectively. For furfural reduction, NADH-dependent activity was also observed in SsAdh1p and NAD(P)H-dependent activities were also observed in SsAdh5p and SsAdh7p. For HMF reduction, NADPH-dependent activities were also observed in SsAdh5p and SsAdh7p. SsAdh4p displayed the highest NADPH-dependent specific activity and catalytic efficiency for reduction of both furfural and HMF among the seven alcohol dehydrogenases. Enzyme activities of all SsADH proteins were more stable under acidic condition. For most SsADH proteins, the optimum temperature for enzyme activities was 30 °C and more than 50 % enzyme activities remained at 60 °C. Reduction activities of formaldehyde, acetaldehyde, isovaleraldehyde, benzaldehyde, and phenylacetaldehyde were also observed in some SsADH proteins. Our results indicate that multiple alcohol dehydrogenases in S. stipitis are involved in the detoxification of aldehyde inhibitors derived from lignocellulosic biomass conversion.

Universal platform for accurately damage-free mapping of sEVs cargo information.

SEVs (small extracellular vesicles) contents signatures appear to mirror pathological changes of diseases, and mapping sEVs contents profile is a promising approach for non-invasive diagnosis of the disease. Herein, we propose a universal system for accurately and damage-freely mapping of sEVs content profile using dual-recognition triggered CHA (catalytic hairpin assembly) and DNAzyme based signal amplification strategy. After immunoassay based capture of CD63 positive sEVs by anti-CD63 lgG coated on the surface of polystyrene plates, probes are incubated with fixed sEVs to penetrate sEVs membrane and act to sense sEVs contents. In detection step, integrated CHA and DNAzyme based strategy is initiated by released initiator from capture probe after recognizing targets, forming a dual circle signal recycling process, realizing signal amplification for high sensitivity. Given the attractive analytical features that i) a universal platform for indistinctive sEVs nucleic acids and protein molecules detection; ii) high sensitivity derived from dual circle signal recycling process; iii) enzyme-free characteristic of integrated CHA and DNAzyme minimizes the interference to sEVs biological activity; iv) mapping of sEVs contents profiles indicates a brand-new strategy for non-invasive diagnosis of the disease, the present approach shows great promise for analyzing additional different analytes in clinical and experimental researches.

Biodegradable polymer-coated versus durable polymer-coated sirolimus-eluting stents: the final 5-year outcomes of the I-LOVE-IT 2 trial.

AIMS: This analysis presents the final five-year results of the I-LOVE-IT 2 trial, a non-inferiority study comparing a biodegradable polymer (BP) sirolimus-eluting stent (SES) with a durable polymer (DP) SES in patients with coronary artery disease. METHODS AND RESULTS: Overall, 2,737 Chinese patients eligible for coronary stenting were treated with BP-SES or DP-SES in a 2:1 ratio. Patients who were randomised to the BP-SES group were additionally re-randomised to receive either six-month or 12-month dual antiplatelet therapy (DAPT) in a 1:1 ratio. The primary endpoint was 12-month target lesion failure (TLF: cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularisation). At five years, the overall follow-up rate was 90.8%, and the cumulative incidence of TLF as the primary endpoint was similar between BP-SES and DP-SES (hazard ratio [HR] 1.01, 95% confidence interval [CI]: 0.79 to 1.28), as was that for the patient-oriented composite endpoint (PoCE: all-cause death, all MI and any revascularisation) (HR 1.03, 95% CI: 0.86 to 1.23), or definite/probable stent thrombosis (ST) (HR 0.91, 95% CI: 0.70 to 1.77). Cumulative events were also similar between the six-month DAPT and 12-month DAPT groups after BP-SES implantation. CONCLUSIONS: I-LOVE-IT 2 showed that the five-year safety and efficacy of BP-SES and DP-SES were similar, as were those between six months and 12 months of DAPT after BP-SES implantation.

An integrated pericardial valved stent special for percutaneous tricuspid implantation: an animal feasibility study.

BACKGROUND: Various percutaneous valve replacement approaches have been reported in animals to replace the aortic and pulmonary valve. To broaden the indications of percutaneous approach to atrioventricular valves replacement, we developed a novel valved stent and evaluated the feasibility and safety of percutaneous implantation of the device in the tricuspid position. MATERIALS AND METHODS: A unidirectional semilunar valve of porcine pericardium was sutured to a valvular ring. Then the ring with pericardial valve was mounted on a double-edge nitinol stent to construct the tricuspid valved stent. Transcatheter tricuspid valved stent implantation was performed on 10 healthy sheep. These sheep were followed up shortly after procedure with echocardiography evaluation and 64-slice CT imaging examination during the periodical follow-up at 1 mo and at 6 mo post-implantation. Additionally, two sheep were sacrificed after the procedure for anatomic and histological evaluation one at 1 h and the other at 1 mo, respectively. RESULTS: Percutaneous valve implantation was successful in eight of 10 sheep. Two sheep died during the procedure due to migration of stent and fatal arrhythmia. The pressure of right heart did not significantly change after the procedure. Further echocardiography and imaging confirmed the stents were in desired position during the follow-up. The remaining six sheep with normal valvular and cardiac functionality survived for 6 mo after implantation. CONCLUSIONS: The tricuspid stent with a valvular ring and pericardial valve can be implanted in tricuspid annulus percutaneous. The double-edge stent could substitute the native tricuspid valve chronically.

A new pan-nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.

BACKGROUND: The Amplatzer ventricular septal defect (VSD) occluder has a fixed stainless steel pin bottom protruding out of the surface at the center of the discs on both sides. Theoretically, this protruding bottom may interfere with epithelialization or, in some cases, cause thrombosis. OBJECTIVE: To evaluate a new type of pan-nitinol VSD occluder without the protruding stainless steel pin bottom on both sides in a canine VSD model designed to ensure safety, effectiveness, and feasibility. METHODS AND RESULTS: VSDs were successfully created by transseptal ventricular septal puncture with a Brockenbrough needle and dilation with an 8-mm-diameter balloon via the right jugular vein in 9 out of 12 canines. The new type VSD occluder was successfully implanted in 8 of the 9 modeled canines. No procedure- or device-related complication was observed. Transthoracic echocardiography and MRI 2 months after device implantations showed that there was no device dislocation or heart valve dysfunction in 6 of the 8 tested canines. In addition, gross and pathological examinations 3-6 months after implantation showed no corrosion of the devices or serious inflammatory reactions in the modeled animals. Complete endothelialization was seen over the surface of the discs. CONCLUSIONS: The new pan-nitinol VSD device can be successfully implanted in a canine VSD model via a transcatheter approach featuring high success rate, low risk of procedure-related complications, and sound biocompatibility. The result suggests that this new VSD occluder could be used safely in future clinical trials for further test.

Combined use of coils and Onyx for transcatheter closure of coronary artery fistulae.

AIMS: The aim of this study was to evaluate the safety and efficacy of combined endovascular coiling and Onyx embolisation in patients with a coronary artery fistula (CAF). METHODS AND RESULTS: Between September 2014 and September 2016, 26 patients with CAFs were enrolled in our study for attempted combined therapy using coils and Onyx. The mean age of patients was 64.0±9.5 years (range, 44-78 years). CAFs were large in 10 and medium in 16 patients. The mean number of coils used was 3.1±1.2 (range, two to six), and the average volume of Onyx was 0.4±0.1 ml (range, 0.2-0.6 ml). Immediate post-embolisation angiography demonstrated that complete occlusion was achieved in 23 patients (88.5%) and a small residual fistula was achieved in three patients (11.5%). Follow-up imaging (median, 11.5 months; range, nine to 20) revealed stable occlusion of CAF in 21 cases (80.8%), trivial recanalisation in four cases (15.4%), and large recanalisation in only one case (3.8%). Re-closure was performed in the patient with large recanalisation. During the follow-up period, no deaths, severe procedure-related complications, or new symptoms occurred. CONCLUSIONS: In selected patients with CAF, transcatheter embolisation in combined therapy using coils and Onyx appears to be a valid option, providing a high success rate and low rate of recanalisation.

A new coated nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.

AIMS: This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. METHODS AND RESULTS: VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. CONCLUSION: The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization.

Pan-nitinol occluder and special delivery device for closure of patent ductus arteriosus: a canine-model feasibility study.

The aim of this study was to evaluate a new type of occluder for patent ductus arteriosus. Patent ductus arteriosus was established in a canine model by anastomosing a length of autologous jugular vein to the descending aorta and the left pulmonary artery in an end-to-side fashion. Transcatheter closure of each patent ductus arteriosus was performed on 10 dogs, which were then monitored for as long as 6 months with aortography, echocardiography, and histologic evaluation. Transcatheter closure with use of the novel pan-nitinol device was successful in all canine models. Postoperative echocardiography showed that the location and shape of the occluders were normal, without any residual shunting. Further histologic evaluation confirmed that the occluder surface was completely endothelialized 3 months after implantation. Transcatheter patent ductus arteriosus closure with the pan-nitinol occluder can be performed safely and successfully in a canine model and shows good biological compatibility and low mortality rates.