Emergence of colistin-resistant Acinetobacter modestus harbouring the intrinsic phosphoethanolamine transferase EptA.

OBJECTIVES: Colistin-resistant Gram-negative pathogens have become a serious worldwide medical problem. This study was designed to reveal the effects of an intrinsic phosphoethanolamine transferase from Acinetobacter modestus on Enterobacterales. METHODS: A strain of colistin-resistant A. modestus was isolated from a sample of nasal secretions taken in 2019 from a hospitalised pet cat in Japan. The whole genome was sequenced by next generation sequencing, and transformants of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae harbouring the phosphoethanolamine transferase-encoding gene from A. modestus were constructed. Lipid A modification in E. coli transformants was analysed using electrospray ionization mass spectrometry. RESULTS: Sequencing of the entire genome revealed that the isolate harboured a phosphoethanolamine transferase-encoding gene, eptA_AM, on its chromosome. Transformants of E. coli, K. pneumoniae, and E. cloacae harbouring both the promoter and eptA_AM gene from A. modestus had 32-fold, 8-fold, and 4-fold higher minimum inhibitory concentrations (MICs) for colistin, respectively, than transformants harbouring a control vector. The genetic environment surrounding eptA_AM in A. modestus was similar to that surrounding eptA_AM in Acinetobacter junii and Acinetobacter venetianus. Electrospray ionization mass spectrometry analysis revealed that EptA_AM modified lipid A in Enterobacterales. CONCLUSION: This is the first report to describe the isolation of an A. modestus strain in Japan and show that its intrinsic phosphoethanolamine transferase, EptA_AM, contributes to colistin resistance in Enterobacterales and A. modestus.

Predictors of Irregular Protrusion After Everolimus-Eluting Stent Implantation in Patients with Stable Coronary Artery Disease.

This study aimed to investigate clinical and preintervention optical coherence tomography (OCT) findings to predict irregular protrusion (IRP) immediately after stent implantation.We evaluated 84 lesions treated with cobalt-chromium everolimus-eluting stent (CoCr-EES) from the MECHANISM Elective study. Patients were divided into two groups according to the presence of IRP [IRP: n = 16, non-IRP: n = 68]. Optical coherence tomography images before intervention and immediately after stenting were evaluated with standard qualitative and quantitative OCT analyses.Total cholesterol and the prevalence of ruptured plaque before intervention were significantly higher in the IRP group than in the non-IRP group [199 ± 37 mg/dL versus 176 ± 41 mg/dL; P = 0.022, 31% versus 7%; P = 0.008]. Total lipid length tended to be longer in the IRP group than in the non-IRP group [19.6 ± 9.2 mm versus 15.5 ± 9.3 mm; P = 0.090]. The prevalence of ruptured plaque, and total cholesterol levels were independent predictors of IRP immediately after stenting by multivariate logistic regression analysis [OR: 4.6, 95% confidence interval: 1.01-21.23, P = 0.048, OR: 1.02, 95% confidence interval: 1.00-1.03, P = 0.046]. IRP post-CoCr-EES implantation was completely resolved at follow-up OCT.The prevalence of ruptured plaque before intervention and total cholesterol levels were independent predictors of IRP after CoCr-EES implantation in patients with stable coronary artery disease.

Comparison of serial optical coherence tomography imaging following aggressive stent expansion technique: insight from the MECHANISM study.

To compare early vascular healing following cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation between groups with or without aggressive stent expansion in patients treated by CoCr-EES for stable coronary artery disease (CAD). Seventy-one stable CAD lesions underwent CoCr-EES implantation and analysis of serial optical coherence tomography (OCT) images obtained post-procedure and at early-term (1- or 3-month) follow-up. The endpoints of this study were neointimal thickness at the time of 1- or 3-month OCT and presence and healing of stent edge dissection. Aggressive stent expansion was defined as a lesion complying with ILUMIEN III sizing protocol; that is, external elastic lamina (EEL) diameter minus maximum balloon diameter ≤ 0.25 mm.  Comparing groups with and without aggressive stent expansion, median neointimal thickness at 1 and 3 months after CoCr-EES implantation was similar (1 month: 0.031 mm vs. 0.041 mm, respectively, p = 0.27; 3 months: 0.036 mm vs. 0.040 mm, respectively, p = 0.84). Regarding stent edge findings, the presence of any stent edge dissection immediately after percutaneous coronary intervention was also similar between the groups (25% vs. 15%, respectively; p = 0.30) and most stent edge dissections resolved completely within 3 months, regardless of location or dissection severity. After 1 year, no clinically driven target lesion revascularization or stent thrombosis was observed in either cohort. Even after aggressive stent expansion, early neointimal proliferation appeared modest with CoCr-EES implantation, and most stent edge dissections had resolved by 3 months. These findings may support the feasibility of EEL-based sizing by pre-stenting OCT.

Cut-off value of strut-vessel distance for the resolution of acute incomplete stent apposition in the early phase using serial optical coherence tomography after cobalt-chromium everolimus-eluting stent implantation.

OBJECTIVE: The purpose of this study was to identify a cut-off value to predict the resolution of incomplete-stent-apposition (ISA) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation at early follow-up. BACKGROUND: To date, appropriate stent apposition at the acute period using intracoronary imaging has been recommended because persistent ISA is considered to be a risk factor for stent thrombosis. We examined the indices for resolving acute ISA. In particular, we determined the cut-off value for strut vessel distance (SV-distance) as visualized by optical coherence tomography (OCT) at 8 months after CoCr-EES implantation. However, the cut-off value of SV-distance for the earlier resolution of ISA is unclear. METHODS: A total of 95 cases and 103 stents were registered in the MECHANISM Elective substudy. The SV-distance was measured at the deepest site of the target malapposition and every 1 mm from the proximal edge to the distal edge of the mal-apposed area using OCT. Cut-off values for ISA resolution at 1 and 3 months were estimated by SV-distance using receiver operating characteristic analysis. RESULTS: The total number of analyzed struts was 14,418 at the 1-month follow-up and 11,986 at the 3-month follow-up. The optimal SV-distance cut-off values just after stent implantation to predict ISA resolution were 185 µm at the 1-month follow-up and 195 µm at the 3-month follow-up. CONCLUSION: For resolution of ISA, SV-distance cut-off values of 185 µm at 1 month postimplantation and 195 µm at 3 months postimplantation can be used as the index of endpoint of the percutaneous coronary intervention.

Cut-off value of mal-apposition volume and depth for resolution at early phase of acute incomplete stent apposition after CoCr-EES implantation.

The purpose of this study was to clarify a cut-off value for acute incomplete stent apposition (ISA) volume and maximum-depth to predict ISA resolution at 1- and 3-month follow-up in patients treated with cobalt-chromium everolimus-eluting stents. In total, 95 cases and 103 stents were registered in the MECHANISM-Elective sub-study. Acute ISA-volume was measured by the trapezoid rule. ISA resolution of cut-off value at 1- and 3-month was estimated by ISA-volume and maximum-depth using receiver operatorating characteristic curve analysis. The total number of analysed acute ISAs was 202 in the 1-month group and 225 in the 3-month group. A total of 123 ISAs at 1-month and a total of 169 ISAs at 3-month had been resolved. The cut-off value of ISA resolution by ISA-volume was 0.169 mm3 at 1-month (AUC: 0.725, sensitivity: 72.2%, specificity: 61.0%) and 0.295 mm3 at 3-month (AUC: 0.757, sensitivity: 75.0%, specificity: 60.4%). The cut-off value of ISA resolution by ISA maximum-depth demonstrated was 0.285 mm at 1-month (area under curve (AUC): 0.789, sensitivity: 70.9%, specificity: 69.9%) and 0.305 mm at 3-month (AUC: 0.663, sensitivity: 60.7%, specificity: 66.9%). Incidence of ISA resolution was significantly lower in combination with cut-off values of ISA-volume and maximum-depth (33%, p < 0.001, at 1-month; 56%, p = 0.003, at 3-month). Combining the cut-off value of ISA-volume with the maximum-depth might be helpful to consider the endpoint of the PCI procedure.

Coronary risk factors associated with OCT macrophage images and their response after CoCr everolimus-eluting stent implantation in patients with stable coronary artery disease.

BACKGROUND AND AIMS: The aim of this study was to evaluate the accumulation of optical coherence tomography (OCT)-macrophages and OCT findings after CoCr everolimus-eluting stent placement, in addition to coronary risk factors. METHODS: A total of 89 lesions in 89 patients were registered in the 1- and 3-month cohort of the multi-centre study. Lesion characteristics and post-procedure OCT images were evaluated immediately and 1 and 3 months after stenting. Patients were divided into low and high macrophage grade groups based on the median macrophage grade. RESULTS: Low-density lipoprotein cholesterol (LDL-C) levels, the prevalence of diabetes mellitus, HbA1c and blood glucose levels in the high macrophage grade group were significantly higher than in the low macrophage grade group (p = 0.025, p = 0.040, p = 0.032, and p = 0.010). Moreover, total lipid arc and length and number of thin-cap fibroatheromas (TCFAs) in the high macrophage grade group were significantly higher than in the low macrophage group (p = 0.008, p = 0.002, and p = 0.012). After CoCr everolimus-eluting stenting, there was a trend towards a greater number, height, and area of irregular protrusions in the high macrophage grade group compared to the low macrophage grade group (p = 0.091, p = 0.059, and p = 0.085). Multivariate logistic regression analysis showed that diabetes mellitus was a significant predictor of high macrophage grades (odds ratio: 2.8, 95% CI: 1.1-7.3, p = 0.030). CONCLUSIONS: The accumulation of OCT-macrophages was associated with diabetes mellitus in patients with coronary artery disease. Moreover, macrophage accumulation and diabetes mellitus may be associated with irregular protrusions just after stenting.

Plasma B-type natriuretic peptide level and cardiovascular events in chronic kidney disease in a community-based population.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels are confounded by renal dysfunction, so this study examined whether plasma BNP might be a reliable biomarker of the onset of cardiovascular (CV) events in a population-based cohort with impaired renal function. METHODS AND RESULTS: Baseline data, including plasma BNP, serum creatinine, and urinary protein levels, were determined in participants from a community-based population. Estimated glomerular filtration rate (eGFR) was calculated, and chronic kidney disease (CKD) was defined as either: eGFR <60 mlxmin(-1)x1.73 m(-2) and/or proteinuria (CKD definition-1) or GFR <60 mlxmin(-1)x1.73 m(-2) (CKD definition-2). The CV endpoint was surveyed prospectively. The cohorts were followed for 5,275 person-years for CKD definition-1, and for 4,350 person-years for CKD definition-2. The CV event-free survival rate in the highest BNP quartile in either CKD definition was the lowest among the quartile groups (P<0.001). In multivariate Cox regression models adjusted by traditional CV risk factors and atrial fibrillation, relative risk (RR) for CV events was significantly higher in the highest BNP quartile compared with the lowest BNP quartile (CKD definition-1, RR 3.51, P<0.01: CKD definition-2, RR 4.67, both P<0.01). CONCLUSIONS: Plasma BNP level provides strong predictive information about the future onset of CV events in CKD subjects selected from the general population.

Gender-specific risk stratification with plasma B-type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population.

BACKGROUND: Elevated plasma B-type natriuretic peptide (BNP) levels suggest a high risk for future onset of cardiovascular events including congestive heart failure (CHF) and mortality. In the general population, although median plasma BNP levels have been reported to be higher in women than in men, the incidence of CHF and mortality are lower in women. However, no studies have examined gender-specific risk stratification of plasma BNP levels for future onset of CHF and mortality. METHODS: Subjects of this study were recruited from our general population. Baseline data including plasma BNP were determined in 13,466 subjects (men 4527, women 8939; median age = 64 yrs). A multivariate Cox regression analysis was performed to examine the predictive ability of plasma BNP for new onset of CHF and mortality. RESULTS: The mean follow-up duration was 2.9 years. After adjustment for traditional cardiovascular risk factors including atrial fibrillation, hazard ratios for CHF development for values above the 75th percentile of BNP were 13.4 (p<0.001) in men and 8.5 (p<0.001) in women. Similarly, each increment of 1SD in log BNP levels increased the hazard ratio by 8.8 (p<0.001) in men, and 6.7 (p<0.001) in women. The area under the receiver operating characteristic curve was significant for prediction of the onset of CHF (men; 0.853, women; 0.838). In addition, increased plasma BNP levels implied high risk of any-cause mortality in men (above the 75th percentile; hazard ratio = 1.8, p=0.005: increment of 1SD; hazard ratio = 1.4, p=0.024), but this relationship was suboptimal in women. CONCLUSION: Measurements of plasma BNP provides strong predictive information about future onset of CHF in both sexes, with predictive ability for death being effective especially in men.

Predictive value of plasma B-type natriuretic peptide for ischemic stroke: a community-based longitudinal study.

OBJECTIVE: Structural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults. METHODS: Subjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke. RESULTS: During a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09). CONCLUSION: Elevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.