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Fulltext First Report of Bleeding Canker of Pear Tree Trunks Caused by Dickeya fangzhongdai in Korea

Choi ED, Kim Y, Lee Y, Jeong MH, Kim GH, Song JH, et al.

Plant Dis, 2021 Feb 16.
PMID: 33591825 DOI: 10.1094/PDIS-09-20-1948-PDN

Pears (Pyrus pylifolia L.) are cultivated nationwide as one of the most economically important fruit trees in Korea. At the end of October 2019, bleeding canker was observed in a pear orchard located in Naju, Jeonnam Province (34°53'50.54″ N, 126°39'00.32″ E). The canker was observed on trunks and branches of two 25-year-old trees, and the diseased trunks and branches displayed partial die-back or complete death. When the bark was peeled off from the diseased trunks or branches, brown spots or red streaks were found in the trees. Bacterial ooze showed a rusty color and the lesion was sap-filled with a yeasty smell. Trunks displaying bleeding symptoms were collected from two trees. Infected bark tissues (3 × 3 mm) from the samples were immersed in 70% ethanol for 1 minute, rinsed three times in sterilized water, ground to fine powder using a mortar and pestle, and suspended in sterilized water. After streaking each suspension on Luria-Bertani (LB) agar, the plates were incubated at 25°C without light for 2 days. Small yellow-white bacterial colonies with irregular margins were predominantly obtained from all the samples. Three representative isolates (ECM-1, ECM-2 and ECM-3) were subjected to further characterization. These isolates were cultivated at 39 C, and utilized (-)-D-arabinose, (+) melibiose, (+)raffinose, mannitol and myo-inositol but not 5-keto-D-gluconate, -gentiobiose, or casein. These isolates were identified as Dickeya sp. based on the sequence of 16S rRNA (MT820458-820460) gene amplified using primers 27f and 1492r (Heuer et al. 2000). The 16S rRNA sequences matched with D. fangzhongdai strain ND14b (99.93%; CP009460.1) and D. fangzhongdai strain PA1(99.86%; CP020872.1). The recA, fusA, gapA, purA, rplB, and dnaX genes and the intergenic spacer (IGS) regions were also sequenced as described in Van der wolf et al. (2014). The recA (MT820437-820439), fusA (MT820440-820442), gapA (MT820443-820445), purA (MT820446-820448), rplB (MT820449-820451), dnaX (MT820452-820454) and IGS (MT820455-820457) sequences matched with D. fangzhongdai strains JS5, LN1 and QZH3 (KT992693-992695, KT992697-992699, KT992701-992703, KT992705-992707, KT992709-992711, KT992713-992715, and KT992717-992719, respectively). A neighbor-joining phylogenetic analysis based on the concatenated recA, fusA, gapA, purA, rplB, dnaX and IGS sequences placed the representative isolates within a clade comprising D. fangzhongdai. ECM-1 to 3 were grouped into a clade with one strain isolated from waterfall, D. fangzhongdai ND14b from Malaysia. Pathogenicity test was performed using isolate ECM-1. Three two-year-old branches and flower buds on 10-year-old pear tree (cv. Nittaka), grown at the National Institute of Horticultural and Herbal Science Pear Research Institute (Naju, Jeonnam Province in Korea), were inoculated with 10 μl and 2 μl of a bacterial suspension (108 cfu/ml), respectively, after wounding inoculation site with a sterile scalpel (for branch) or injecting with syringe (for flower bud). Control plants were inoculated with water. Inoculated branches and buds in a plastic bag were placed in a 30℃ incubator without light for 2 days (Chen et al. 2020). Both colorless and transparent bacterial ooze and typical bleeding canker were observed on both branches and buds at 3 and 2 weeks post inoculation, respectively. No symptoms were observed on control branches and buds. This pathogenicity assay was conducted three times. We reisolated three colonies from samples displaying the typical symptoms and checked the identity of one by sequencing the dnaX locus. Dickeya fangzhongdai has been reported to cause bleeding canker on pears in China (Tian et al. 2016; Chen et al. 2020). This study will contribute to facilitate identification and control strategies of this disease in Korea. This is the first report of D. fangzhongdai causing bleeding canker on pears in Korea.
Fulltext Polymer-free sirolimus-eluting stents in a large-scale all-comers population

Krackhardt F, Kočka V, Waliszewski MW, Utech A, Lustermann M, Hudec M, et al.

Open Heart, 2017 06 06;4(2):e000592.
PMID: 28761678 DOI: 10.1136/openhrt-2017-000592

OBJECTIVE: The objective of this study was to assess the safety and efficacy of a polymer-free sirolimus coated, ultrathin strut drug-eluting stent (PF-SES) in an unselected patient population with a focus on acute coronary syndrome (ACS). Furthermore, stable coronary artery disease (CAD) with short (≤6 months) versus long (>6 months) dual antiplatelet therapy (DAPT) were also studied.
METHODS: Patients who received PF-SES were investigated in an unselected large-scale international, single-armed, multicenter, 'all comers' observational study. The primary endpoint was the 9-month target lesion revascularisation (TLR) rate, whereas secondary endpoints included the 9-month major adverse cardiac events (MACE) and procedural success rates. A priori defined subgroups such as patients with ACS, diabetes, lesion subsets and procedural characteristics relative to DAPT were investigated.
RESULTS: A total of 2877 patients of whom 1084 had ACS were treated with PF-SES (1.31±0.75 stents per patient). At 9 months, the accumulated overall TLR rate was 2.3% (58/2513). There was no significant difference between ACS and stable CAD (2.6% vs 2.1%, p=0.389). However, the overall MACE rate was 4.3% (108/2513) with a higher rate in patients with ACS when compared with the stable CAD subgroup (6.1%, 58/947 vs 3.2%, 50/1566, p<0.001).
CONCLUSIONS: PF-SES angioplasty is safe and effective in the daily clinical routine with low rates of TLR and MACE in an unselected patient population. Our data are in agreement with prior clinical findings that extended DAPT duration beyond 6 months do not improve clinical outcomes in patients with stable CAD (ClinicalTrials.gov Identifier NCT02629575).
TRIAL REGISTRATION NUMBER: NCT02629575.
Fulltext Real-World Dual Antiplatelet Therapy Following Polymer-Free Sirolimus-Eluting Stent Implantations to Treat Coronary Artery Disease

Krackhardt F, Waliszewski M, Kočka V, Toušek P, Janek B, Hudec M, et al.

Cardiovasc Drugs Ther, 2020 06;34(3):335-344.
PMID: 32212061 DOI: 10.1007/s10557-020-06963-5

OBJECTIVES: The objective of this post hoc analysis was to analyze real-world dual antiplatelet therapy (DAPT) regimens following polymer-free sirolimus-eluting stent (PF-SES) implantations in an unselected patient population.
METHODS: Patient-level data from two all-comers observational studies (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled and analyzed in terms of their primary endpoint. During the data verification process, we observed substantial deviations from DAPT guideline recommendations. To illuminate this gap between clinical practice and guideline recommendations, we conducted a post hoc analysis of DAPT regimens and clinical event rates for which we defined the net adverse event rate (NACE) consisting of target lesion revascularization (TLR, primary endpoint of all-comers observational studies) all-cause death, myocardial infarction (MI), stent thrombosis (ST), and bleeding events. A logistic regression was utilized to determine predictors why ticagrelor was used in stable coronary artery disease (CAD) patients instead of the guideline-recommended clopidogrel.
RESULTS: For stable CAD, the composite endpoint of clinical, bleeding, and stent thrombosis, i.e., NACE, between the clopidogrel and ticagrelor treatment groups was not different (5.4% vs. 5.1%, p = 0.745). Likewise, in the acute coronary syndrome (ACS) cohort, the NACE rates were not different between both DAPT strategies (9.2% vs. 9.3%, p = 0.927). There were also no differences in the accumulated rates for TLR, myocardial infarction ([MI], mortality, bleeding events, and stent thrombosis in elective and ACS patients. The main predictors for ticagrelor use in stable CAD patients were age
Fulltext Trial of everolimus-eluting stents or bypass surgery for coronary disease

Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al.

N Engl J Med, 2015 Mar 26;372(13):1204-12.
PMID: 25774645 DOI: 10.1056/NEJMoa1415447

BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.
METHODS: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.
RESULTS: After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.
CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).
Fulltext Unrestricted use of polymer-free sirolimus eluting stents in routine clinical practice

Krackhardt F, Kočka V, Waliszewski M, Toušek P, Janek B, Trenčan M, et al.

Medicine (Baltimore), 2020 Feb;99(8):e19119.
PMID: 32080086 DOI: 10.1097/MD.0000000000019119

Stent designs with ultrathin struts may further increase the procedural success of challenging lesion subsets. The objective of this study was to assess the safety and efficacy of ultrathin strut, polymer-free sirolimus eluting stent (PF-SES) implantations in a large scale, unselected patient population.Adult patients underwent percutaneous coronary interventions (PCI) with a thin-strut PF-SES. Data from two all-comers observational studies having the same protocol (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled. The accumulated target lesion revascularization (TLR) rate at 9-12 months was the primary endpoint. All dual antiplatelet therapy strategies according to the applicable guidelines were permissible.In total, 7243 patients were prospectively enrolled for PCI with PF-SES in stable coronary artery disease or acute coronary syndrome (ACS). Major risk factors in the overall cohort were diabetes (37.3%), ST elevation myocardial infarction (18.1%) and non-ST myocardial infarction (24.6%). The follow-up rate was 88.6% in the overall population. The TLR rate in the overall cohort was 2.2% whereas definite/probable stent thrombosis (ST) occurred in 0.7%. In patients with in-stent restenosis lesions, the major adverse cardiac events rate was 6.4% whereas the corresponding rate for isolated left main coronary artery (LMCA) disease was highest with 6.7% followed by patients with culprit lesions in vein bypasses (VB, 7.1%). The mortality rate in patients treated in VB lesions was highest with 5.4%, followed by the isolated LMCA subgroup (3.4%) and ACS (2.6%).PCI with PF-SES in an unselected patient population, is associated with low clinical event and ST rates. Furthermore, PF-SES angioplasty in niche indications demonstrated favorable safety and efficacy outcomes with high procedural success rates.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease: Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial

Ahn JM, Kang DY, Yun SC, Ho Hur S, Park HJ, Tresukosol D, et al.

Circulation, 2022 Nov 22;146(21):1581-1590.
PMID: 36121700 DOI: 10.1161/CIRCULATIONAHA.122.062188

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease.
METHODS: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization.
RESULTS: During a median follow-up of 11.8 years (interquartile range, 10.6-12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88-1.56]; P=0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75-1.53]; P=0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65-1.67]; P=0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06-3.27]; P=0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58-2.32]; P<0.001) were more frequent after PCI than after CABG.
CONCLUSIONS: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up.
REGISTRATION: URL: https://www.
CLINICALTRIALS: gov; Unique identifiers: NCT05125367 and NCT00997828.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study

Kim H, Kang DY, Ahn JM, Lee J, Choi Y, Hur SH, et al.

JACC Cardiovasc Interv, 2023 Oct 09;16(19):2412-2422.
PMID: 37821187 DOI: 10.1016/j.jcin.2023.07.028

BACKGROUND: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD).
OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial.
METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years).
RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group.
CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).