Structure-activity relationships of bensulfuron methyl and its derivatives as novel agents against drug-resistant Candida auris.

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug-tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 µM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 µM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta-position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure-activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.

Treating radiation­related nasopharyngeal necrosis with endostar in patient with nasopharyngeal carcinoma: A report of two cases and a literature review.

Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.

Facile synthesis, crystal structure, quantum calculation, and biological evaluations of novel selenenyl sulfide compounds as potential agrochemicals.

BACKGROUND: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS). RESULTS: All the target compounds were characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, selenium-77 (77 Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed. Compounds 10d, 10h, 10s, 10u, 10aa, 10ac, 10ae, 10ag, and 10ai exhibited 40%, 43%, 39%, 41%, 47%, 46%, 47%, 42%, and 39% anti-TMV activities at 500 mg L-1 , better than that of ribavirin. The median effective concentration (EC50 ) against Sclerotinia sclerotiorum of 10ac was 6.69 mg L-1 and EC50 values against Physalospora piricola and Pyricularia grisea of 10z were 12.25 mg L-1 and 15.27 mg L-1 , respectively, superior to the corresponding values of chlorothalonil. Compounds 10c and 10v demonstrated 100% larvicidal activity against Culex pipiens pallens at 5 mg L-1 , while 10a displayed 100% insecticidal activity against Mythimna separata at 200 mg L-1 . Compounds 10c, 10j, and 10o showed > 60% inhibitions against plant AHAS at 10 µmol L-1 . From the quantum calculation, highest occupied molecular orbital (HOMO) was considered as a factor that affects the anti-TMV activity. CONCLUSION: The preliminary results suggested that more efforts should be devoted to exploring the selenenyl sulfides for the discovery of new leads of antiviral agent, fungicide, insecticide or AHAS inhibitors as potential agrochemicals for crop protection. © 2023 Society of Chemical Industry.

Chemical preparation, degradation analysis, computational docking and biological activities of novel sulfonylureas with 2,5-disubstituted groups.

Based on the previous finding that a substitution at 5-position of the benzene ring is favorable to enhance the degradation rates of sulfonylurea herbicides, a total of 16 novel 2,5-disubsituted sulfonylurea compounds were chemically synthesized and fully characterized by means of 1H NMR, 13C NMR, HRMS and X-ray diffraction. By using HPLC analysis, the degradation behavior of M03, a compound belonging to this family, was studied and confirmed that chlorsulfuron itself is not a degraded product of the 2,5-disubstituted sulfonylureas. Inhibition constants against plant acetohydroxyacid synthase (AHAS) were determined for selected compounds, among which SU3 showed seven times stronger activity against the mutant W574L enzyme than chlorsulfuron. Molecular docking suggested that the substituted group at 5-position of benzene ring is likely to interact with the surrounding residues Met200 and Asp376 of AtAHAS. From the greenhouse herbicidal assay and crop safety test, SU5 and SU6 are considered as herbicide candidates to control dicotyledon weeds in corn, while SU3 is likely to be a promising candidate to control dicotyledon weed species and barnyard grass in wheat. The present research has therefore provided some new insights to understand the structure-activity relationships of herbicidal sulfonylureas with di-substitutions at benzene ring.

Tailoring bacterial cellulose structure through CRISPR interference-mediated downregulation of galU in Komagataeibacter xylinus CGMCC 2955.

Diverse applications of bacterial cellulose (BC) have different requirements in terms of its structural characteristics. culturing Komagataeibacter xylinus CGMCC 2955, BC structure changes with alterations in oxygen tension. Here, the K. xylinus CGMCC 2955 transcriptome was analyzed under different oxygen tensions. Transcriptome and genome analysis indicated that BC structure is related to the rate of BC synthesis and cell growth, and galU is an essential gene that controls the carbon metabolic flux between the BC synthesis pathway and the pentose phosphate (PP) pathway. The CRISPR interference (CRISPRi) system was utilized in K. xylinus CGMCC 2955 to control the expression levels of galU. By overexpressing galU and interfering with different sites of galU sequences using CRISPRi, we obtained strains with varying expression levels of galU (3.20-3014.84%). By testing the characteristics of BC, we found that the porosity of BC (range: 62.99-90.66%) was negative with galU expression levels. However, the crystallinity of BC (range: 56.25-85.99%) was positive with galU expression levels; galU expression levels in engineered strains were lower than those in the control strains. Herein, we propose a new method for regulating the structure of BC to provide a theoretical basis for its application in different fields.

Purification optimization for a recombinant single-chain variable fragment against type 1 insulin-like growth factor receptor (IGF-1R) by using design of experiment (DoE).

Design of experiment (DoE) is a statistics-based technique for experimental design that could overcome the shortcomings of traditional one-factor-at-a-time (OFAT) approach for protein purification optimization. In this study, a DoE approach was applied for optimizing purification of a recombinant single-chain variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF-1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level fractional factorial analysis and successively a central composite circumscribed (CCC) design were used to identify the optimal elution conditions. Two main effects, pH and trehalose, were identified, and high recovery (above 95%) and low aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with 32-35% (w/v) trehalose added. In the second step using cation exchange chromatography, an initial screening of media and elution pH and a following CCC design were performed, whereby the optimal selectivity of the scFv was obtained on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5-12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold scale-up experiment. The purities and yields of intermediate and final products all fell within the regions predicted by DoE approach, suggesting the robustness of the optimized conditions. We proposed that the DoE approach described here is also applicable in production of other recombinant antibody constructs.

Co-expression of Dsb proteins enables soluble expression of a single-chain variable fragment (scFv) against human type 1 insulin-like growth factor receptor (IGF-1R) in E. coli.

Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.

Pin1, endothelial nitric oxide synthase, and amyloid-ß form a feedback signaling loop involved in the pathogenesis of Alzheimer's disease, hypertension, and cerebral amyloid angiopathy.

Although the molecular mechanism has not yet been clarified until now, it is very interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral amyloid angiopathy (CAA) often occur synchronously and possess many similar pathological characteristics. Herein, we hypothesize that a feedback signaling loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid-ß (Aß), may contribute to the interesting pathological phenomenon. First, Pin1 inhibits the production of Aß, and enhances the activity of eNOS. Second, Aß and eNOS form a mutual inhibition system. Third, the well-balanced feedback signaling loop avoids the development of AD, HTN, and CAA by inhibiting the frequent pathological characteristics of these diseases, including Aß deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1 and eNOS not only inhibit Aß production but also accelerate Aß clearance, preventing Aß deposition in cerebral microvessels. On the other hand, Pin1 and eNOS promote vasodilatation and prevent the elevation of blood pressure in brain, alleviating the pathology of cerebral microbleeds. However, once the precise balance is disturbed, it may result in Aß deposition, microbleeds, and elevated blood pressure, possibly leading to the synchronous occurrence of AD, HTN, and CAA. The hypothesis updates the current understanding of the molecular linkage among AD, HTN, and CAA, and lays the ground for developing combined prevention, diagnosis, and treatment of these diseases more efficiently and more economically. Interestingly, biotechnical medicines enhancing the activity of Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting Aß deposition may alleviate the clinical pathologies of these related diseases.

Focusing on the structure and the function of Pin1: new insights into the opposite effects of fever on cancers and Alzheimer's disease.

A new molecular mechanism is proposed to explain the opposite effects of fever on cancers and Alzheimer's disease (AD). The proposal is based on the experimental discovery that the fever stress interferes the structure and the activity of Pin1, which plays uniquely opposite roles in the pathogenesis of cancers and AD. Pin1 is the only known cis-trans isomerase that specifically isomerizes the pSer/pThr-Pro motifs in proteins, facilitating kinds of signaling pathways. The up-regulation of Pin1 can amplify multiple oncogenic signaling pathways, resulting in cancers, while the down-regulation of Pin1 can cause many pathological characteristics of AD. Recently, we found that Pin1 is sensitive to heat treatment, and heating can gradually damage both of the structure and the function of Pin1. So, we hypothesize that the fever stress, which is usually induced by febrile diseases or hyperthermia treatment, may lead to the damaged structure of Pin1 and the decreased activity of it in vivo, resulting in the decreased risk of cancers and the increased risk of AD. Numerous epidemiological and experimental researches on cancers and AD support the hypothesis. The hypothesis not only provides new insights into the opposite effects of fever on cancers and AD, but also gives new clues for understanding the interacting effects of the environmental and the genetic factors in the complicated pathogenesis of cancers and AD.

Crush stenting with drug-eluting stents: relevance of coronary bifurcation lesion location on angiographic and clinical outcomes.

BACKGROUND: Data on the relevance of the location of coronary bifurcation lesions treated by crush stenting with outcomes were limited. HYPOTHESIS: We hypothesized that the location of the bifurcation lesion correlated with clinical outcome. METHOD: A total of 212 patients with 230 true bifurcation lesions treated by crush stenting with drug-eluting stents (DES) were assessed prospectively. Surveillance quantitative angiographies were indexed at 8 months after procedure. Primary endpoint was major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, and target lesion revascularization (TLR). RESULTS: Patients in the distal right coronary artery (RCAd) group were characterized by higher proportions of prior myocardial infarction and very tortuous lesions. However, lesions in the RCAd group, compared to those of other groups, had the lowest late lumen loss, with resultant lowest incidence of MACE at a mean follow-up of 268±35 days. Independent predictors of MACE included unsatisfied kissing (KUS; hazard ratio [HR]: 12.14, 95% confidence interval [CI]: 4.01-12.10, P = .001) and non-RCA lesion (HR: 20.69, 95% CI: 5.05-22.38, P = .001), while those of TLR were KUS (HR: 10.21, 95% CI: 0.01-0.34, P = .002), bifurcation angle (HR: 4.728, 95% CI: 2.541-4.109, P = .001), and non-RCA lesion (HR: 16.05, 95%CI: 1.01-4.83, P = .001). CONCLUSIONS: Classical crush stenting with drug-eluting stents is associated with significantly better outcomes in RCAd. Quality of kissing inflation is mandatory to improve outcome.

Clinical outcome after management of unprotected left main in-stent restenosis after bare metal or drug-eluting stents.

BACKGROUND: Implantation of either bare metal stent (BMS) or drug-eluting stent (DES) has been used in every day practice for patients with unprotected left main stenosis (UPLMS). There are still a lack of data regarding the subsequent results of UPLMS in-stent restenosis (ISR). The present study aimed at determining the clinical outcome of UPLMS ISR patients after implantation of either BMS or DES. METHODS: Patients with UPLMS ISR after stenting were included. The primary endpoint was the cumulative major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). RESULTS: UPLMS ISR rate was 14.8% (n = 73, 15.7% after BMS, 14.5% for DES) after average of (3.89 +/- 2.01) years (range from 1 to 10.5 years) follow-up. Angiographic follow-up between 6 - 8 months was available in 85.3%. Of these, repeat percutaneous coronary intervention (PCI) was used in 62 (84.9%) patients, with medicine only in 9 (12.4%) and coronary artery bypass graft (CABG) in 2 (2.7%). Most repeat PCI patients were with unstable angina (87.0%), and had decreased left ventricular ejection fraction ((42.58 +/- 5.12)%), fewer focal/ostial left circumflex branch (LCX) lesions, in relative to medicine only group. After (31.9 +/- 23.3) months, the MACE, MI, TVR and cardiac death were 31.5%, 1.4%, 24.1% and 8.2%, respectively. Definite and possible stent thrombosis occurred in 1 (1.4%) patient. CONCLUSIONS: Medical therapy for asymptomatic isolated ostial LCX was safe. Repeat PCI for UPLMS ISR was associated with acceptable early and short-term clinical outcome. Further study was needed to elucidate the role of CABG in treating UPLMS ISR.

Different edge effects of paclitaxel- and sirolimus-eluting stents on proximal and distal edges in patients with unstable angina: serial intravascular ultrasound analysis.

BACKGROUND: It is unclear whether edge segments have different responses to paclitaxel eluting stent (PES) and sirolimus eluting stent (SES) implantation in patients with unstable angina. This study aimed to compare the different vascular edge responses in patients with unstable angina and single de novo coronary lesion treated with SES and PES. METHODS: Two hundred and fifty-five patients with unstable angina and single de novo lesion were randomly assigned to PES and SES groups. Serial volumetric intravascular ultrasound (IVUS) images were taken immediately after stenting and at an eight-month follow-up. Five-mm edge segments proximal and distal to the stents were analyzed. RESULTS: Baseline characteristics were comparable between the two groups. At proximal-edge segment, the vessel area decreased and the plaque area increased significantly in the PES group as compared with the SES group. A significant net loss of lumen area was found in the PES group (from (11.10 +/- 3.12) mm(2) at baseline to (9.92 +/- 3.59) mm(2) at the follow-up, P < 0.001). At the distal-edge segment, the net loss of lumen area in the PES group (from (7.71 +/- 2.81) mm(2) at baseline to (6.66 +/- 2.29) mm(2) at the follow-up, P < 0.001) was attributed to a significant increase of plaque area. Proximal-edge stenosis was commonly seen in the PES group (20.0%) as compared with the SES group (5.0%, P = 0.001). This correlated with the higher incidence of target lesion revascularization in the PES group (P = 0.03). Subsegmentally, the smallest Delta lumen area was located at 2 mm proximally in both groups, at 0 mm distally in the PES group, and at 1 mm distally in the SES group. CONCLUSIONS: The two groups demonstrated negative remodeling of edge segments. PES was less effective than SES in inhibiting the growth of plaque within the first 1-mm length proximal to the stent.

Mechanisms and clinical significance of quality of final kissing balloon inflation in patients with true bifurcation lesions treated by crush stenting technique.

BACKGROUND: The mechanisms responsible for the occurrence of a kissing unsatisfied (KUS) result after classical crush stenting remain unclear. The present study aimed at analyzing the mechanisms and clinical significance of KUS. METHODS: Two hundred and thirteen patients with true bifurcation lesions treated with classical crush stenting and final kissing balloon inflation (FKBI) were assigned to upper, middle, and lower groups according to the position of the side branch re-wiring assessed by visual estimation, quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS). Angiographic follow-up was indexed at 12 months. RESULTS: The upper group was characterized by a larger bifurcation angle of 55.53 degrees +/- 25.25 degrees (P = 0.030) and a longer procedural time (42.43 +/- 23.92) minutes (P = 0.015). The overall rate of KUS by visual estimation was 10.48%, with 5.4% in the upper group, 3.9% in middle group, and 36.1% in lower group (P < 0.001). For the diagnosis of KUS, visual inspection demonstrated a good correlation with both QCA and IVUS. Smaller stent diameter was the main reason for KUS in the upper group, while extra-stent side wire location, or re-wire in a low position was the main mechanism attributed to KUS in the lower group. The Lower group had more restenosis, with most restenotic lesions at a lower position of the side branch ostium. KUS (HR 1.652, 95% CI 1.332 - 2.088, P < 0.001) and re-wiring position (HR 2.341, 95% CI 1.780 - 4.329, P < 0.001) were two independent predictors of side branch restenosis. Re-wiring position (OR 0.458, 95%CI 0.336 - 0.874, P = 0.001) and side stent expansion (OR 3.122, 95%CI 2.883 - 5.061, P = 0.014) were factors predicting the findings of KUS. CONCLUSIONS: Side wire outside side stents resulted in more KUS and restenosis. Different restenotic lesion types reflected individual mechanisms contributing to the development of plaque proliferation.

Effect of coronary bifurcation angle on clinical outcomes in Chinese patients treated with crush stenting: a subgroup analysis from DKCRUSH-1 bifurcation study.

BACKGROUND: Bifurcation angles may have an impact on the clinical outcomes of crush stenting. We sought to compare high (> or = 60 degrees ) with low (< 60 degrees ) bifurcation angle in patients who underwent either classical or double kissing (DK) crush stenting for bifurcation lesions from the DKCRUSH-1 data base. METHODS: There were 212 patients with 220 lesions, some with low-angle (n = 138) and some with high-angle (n = 74). Angiography was indexed at 8-month after procedure. Primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and target lesion revascularization (TLR). Secondary endpoint included late lumen loss, the rate of restenosis, and final kissing balloon inflation (FKBI). RESULTS: At 8 months, clinical follow-up was 100%; angiographic follow-up was 75% in the low-angle group and 83.3% in the high-angle group. There were no significant differences in the FKBI between the high-angle group (91.43%) and the low-angle group (82.39%). In the high angle group, there was a significant difference in contrast volume used (P = 0.005) but no significant difference in acute gain, minimum lumen diameter (MLD), late loss and diameter stenosis in the pre-bifurcation segment, post-bifurcation segment or side branch. When lesions were assigned into with-(n = 133) and without-FKBI (n = 42), significant side-branch late loss was seen in the group without-FKBI ((0.65 +/- 0.49) mm vs (0.47 +/- 0.62) mm, P = 0.02), with a resultant greater restenosis rate (37.68% vs 18.32%, P = 0.001). No difference was detected in the MACE free survival rate between the high and low angle groups (82.39% vs 82.36%, P = 0.84). The rate of stent thrombosis tended to be higher in the lower-angle group although there was no significant difference (P = 0.38). The TLR free survival rate was 87.2% in the with-FKBI group vs 73.5% in the without-FKBI group (P = 0.001). Cox regression analysis showed that the independent predictors for target vessel revascularization were the side branch stent MLD post stenting (hazard ratios (HR) 1.028, 95% CI 2.357 - 16.233, P = 0.002), lack of FKBI (HR 4.910, 95% CI 4.706 - 8.459, P = 0.001) and unsatisfactory kissing (HR 3.120, 95% CI 2.975 - 5.431, P = 0.001). CONCLUSIONS: Bifurcation angles do not influence the clinical outcome of crush stenting. Successful final kissing balloon inflation, regardless of bifurcation angles, can predict TLR.

Distal left main coronary bifurcation lesions predict worse outcome in patients undergoing percutaneous implantation of drug-eluting stents: results from the Drug-Eluting Stent for the Treatment of Left Main Disease (DISTAL) Study.

OBJECTIVES: We investigated the clinical outcome of stenting of unprotected left main coronary artery (LMCA). METHODS: We studied 164 patients with nonbifurcated LMCA lesions (group A) and 96 patients with distal bifurcated lesions (group B). RESULTS: Clinical follow-up was available in 100%. Angiographic follow-up was 87.3% in group A and 86% in group B (p = 0.922). There were significant differences in major adverse cardiac events at 1 (p = 0.014) and 2 years (p = 0.002) between group B (19.8%, 25.0%) and group A (9.1%, 10.4%), mainly due to increased target-vessel revascularization (16.7, 21.9% in group B vs. 6.1, 7.3% in group A, p = 0.006 and 0.001, respectively). The double-stent technique was associated with worse outcomes at 1 year in group B compared to group A. Bifurcation lesions (HR 3.42, 95% CI 1.34-5.61, p = 0.001), diabetes (HR 2.68, 95% CI 2.01-12.11, p = 0.015), three-vessel disease (HR 0.83, 95% CI 0.27-0.96, p = 0.001), incomplete revascularization (HR 0.15, 95% CI 0.11-0.35, p = 0.001) and stent diameter (HR 5.05, 95% CI 2.71-10.01, p = 0.03) were the independent factors of major adverse cardiac events in the whole patient cohort. CONCLUSION: Stenting unprotected distal bifurcated LMCA was associated with unfavorable results when compared to stenting other LMCA lesions.

Clinical outcomes of percutaneous coronary intervention for chronic total occlusion lesions in remote hospitals without on-site surgical support.

BACKGROUND: The safety of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions in remote hospitals without surgical facilities remains unknown. This study aimed to evaluate three-year outcomes after CTO for PCI in ten centers around China where no on-site coronary artery bypass grafting (CABG) support was available. METHODS: A total of 152 patients from 10 Chinese hospitals without on-site surgical facilities were prospectively studied. Intra-procedural and in-hospital events were assessed. Angiographic follow-up was indexed eight months after the initial procedure. Clinical follow-up was extended to three years. The primary outcome was the rate of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction and target-vessel revascularization (TVR). RESULTS: The incidence of CTO was 7.9% in patients who underwent PCI. Successful recanalization was achieved in 132 patients (86.8%). Compared with patients in the PCI success group, patients with PCI procedural failure had longer lesion lengths ((42.32 +/- 22.08) mm vs (27.61 +/- 22.85) mm, P = 0.023), a higher rate of perforation (25.0% vs 0, P = 0.014), and a greater need for pericardial puncture. There were significant differences in MACE in-hospital and at one year and three years between the failure (10.0%, 30.0% and 35.0%) and the success (3.0%, 12.1% and 14.4%) groups (P = 0.037, 0.034 and 0.040, respectively). These led to a significant decrease in the MACE-free survival rate at one and three years in the failure group, compared with the success group (P = 0.031 and 0.023, respectively). Stump was the only predictor of recanalization success (HR 0.158, 95% CI 0.041-0.612, P = 0.008), whereas procedural failure (OR 13.023, 95% CI 6.67-13.69, P = 0.002), incomplete revascularization (OR 9.71, 95% CI 2.93-5.59, P = 0.005), and total stent length (OR 6.02, 95% CI 1.55-11.93, P = 0.027) were three independent predictors of MACE. CONCLUSIONS: PCI for CTO was unsafe in remote hospitals without CABG facilities. Paying attention to coronary perforation is important for successful procedures.

[Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].

OBJECTIVE: To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions. METHODS: 311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE). RESULTS: Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique. CONCLUSION: DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

Crush stenting in treating coronary bifurcate lesions: paclitaxel eluting stents versus sirolimus eluting stents.

BACKGROUND: Because no data regarding the comparison of crush stenting with paclitaxel (PES) or sirolimus eluting stents (SES) for coronary bifurcate lesions have been reported, we compared the clinical outcomes of these two types of stents. METHODS: Two hundred and thirty patients with 242 bifurcate lesions were enrolled in a prospective, nonrandomized trial. Primary endpoints included myocardial infarction, cardiac death and target vessel revascularization at 8 months. RESULTS: All patients were followed up clinically and 82% angiographically at 8 months. Final kissing balloon inflation was performed in 72% in the PES and 75% in the SES groups (P>0.05). Compared to the SES group, PES group had a higher late loss and incidence of restenosis (P=0.04) in the prebifurcation vessel segment. The postbifurcation vessel segment in the PES group had a greater late loss ((0.7+/-0.6) mm vs (0.3+/-0.4) mm, P<0.001) and higher restenosis in the side branch (25.5% vs 15.6%, P=0.04) when compared to the SES group. There was significant difference of insegment restenosis in the entire main vessel between PES and SES groups (P=0.004). Target lesion revascularization was more frequently seen in the PES group as compared to the SES group (P=0.01). There was significant difference in the accumulative MACE between these two groups (P=0.01). The survival rate free from target lesion revascularization was significantly higher in the SES group when compared to the PES group (P<0.001). CONCLUSION: SES is superior to PES in reducing restenosis and target lesion revascularization by 8-month follow-up after crush stenting for bifurcate lesions.