Increased resistance against tellurite is conferred by a mutation in the promoter region of uncommon tellurite resistance gene tehB in the ter-negative Shiga toxin-producing Escherichia coli O157:H7.

Resistance to potassium tellurite (PT) is an important indicator in isolating Shiga toxin-producing Escherichia coli (STEC) O157:H7 and other major STEC serogroups. Common resistance determinant genes are encoded in the ter gene cluster. We found an O157:H7 isolate that does not harbor ter but is resistant to PT. One nonsynonymous mutation was found in another PT resistance gene, tehA, through whole-genome sequence analyses. To elucidate the contribution of this mutation to PT resistance, complementation of tehA and the related gene tehB in isogenic strains and quantitative RT‒PCR were performed. The results indicated that the point mutation not only changed an amino acid of tehA, but also was positioned on a putative internal promoter of tehB and increased PT resistance by elevating tehB mRNA expression. Meanwhile, the amino acid change in tehA had negligible impact on the PT resistance. Comprehensive screening revealed that 2.3% of O157:H7 isolates in Japan did not harbor the ter gene cluster, but the same mutation in tehA was not found. These results suggested that PT resistance in E. coli can be enhanced through one mutational event even in ter-negative strains. IMPORTANCE: Selective agents are important for isolating Shiga toxin-producing Escherichia coli (STEC) because the undesirable growth of microflora should be inhibited. Potassium tellurite (PT) is a common selective agent for major STEC serotypes. In this study, we found a novel variant of PT resistance genes, tehAB, in STEC O157:H7. Molecular experiments clearly showed that one point mutation in a predicted internal promoter region of tehB upregulated the expression of the gene and consequently led to increased resistance to PT. Because tehAB genes are ubiquitous across E. coli, these results provide universal insight into PT resistance in this species.

Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Shiga toxin 2eB-transgenic lettuce vaccine: N-glycosylation is important for protecting against porcine edema disease.

Porcine edema disease (ED) is a life-threatening toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC) in weaned piglets. We previously reported that the stx2eB-transgenic lettuce 2BH strain shows potential for use as an oral vaccine candidate against ED. However, the 2BH strain expressed a hemagglutinin (HA)-tag together with Stx2eB and contained non-canonical N-glycosylation. Therefore, we developed two Stx2eB-lettuce strains, the 3 (G+) strain in which the HA-tag was removed from 2BH, and the 3 (G-) lettuce strain, in which the 73rd Asn was replaced with Ser to prevent non-canonical N-glycosylation of Stx2eB from the 3 (G+) strain. We examined the protective effect of these newly developed two strains compared with the previous 2BH strain against ED using a colostrum-deprived piglet STEC infection model. We found that the N-glycosylated 2BH and 3 (G+) strains relieved the pathogenic symptoms of ED in STEC-challenged piglets, whereas the non-glycosylated 3 (G-) strain did not. N-Glycosylation of the Stx2eB product in lettuce may be involved in the immune response in piglets.

Shiga toxin 2eB-transgenic lettuce vaccine is effective in protecting weaned piglets from edema disease caused by Shiga toxin-producing Escherichia coli infection.

Porcine edema disease (ED) is a toxemia that is caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC) and is associated with high mortality. Since ED occurs most frequently during the weaning period, preweaning vaccination of newborn piglets is required. We developed stx2eB-transgenic lettuce as an oral vaccine candidate against ED and examined its protective efficacy using a piglet STEC infection model. Two serially developed Stx2eB-lettuce strains, 2BN containing ingredient Stx2eB constituting a concentration level of 0.53 mg Stx2eB/g of powdered lettuce dry weight (DW) and 2BH containing ingredient Stx2eB constituting a concentration level of 2.3 mg of Stx2eB/g of powdered lettuce DW, were evaluated in three sequential experiments. Taken the results together, oral administration of Stx2eB-lettuce vaccine was suggested to relieve the pathogenic symptoms of ED in piglets challenged with virulent STEC strain. Our data suggested that Stx2eB-lettuce is a promising first oral vaccine candidate against ED.

Large-scale genome analysis of bovine commensal Escherichia coli reveals that bovine-adapted E. coli lineages are serving as evolutionary sources of the emergence of human intestinal pathogenic strains.

How pathogens evolve their virulence to humans in nature is a scientific issue of great medical and biological importance. Shiga toxin (Stx)-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are the major foodborne pathogens that can cause hemolytic uremic syndrome and infantile diarrhea, respectively. The locus of enterocyte effacement (LEE)-encoded type 3 secretion system (T3SS) is the major virulence determinant of EPEC and is also possessed by major STEC lineages. Cattle are thought to be the primary reservoir of STEC and EPEC. However, genome sequences of bovine commensal E. coli are limited, and the emerging process of STEC and EPEC is largely unknown. Here, we performed a large-scale genomic comparison of bovine commensal E. coli with human commensal and clinical strains, including EPEC and STEC, at a global level. The analyses identified two distinct lineages, in which bovine and human commensal strains are enriched, respectively, and revealed that STEC and EPEC strains have emerged in multiple sublineages of the bovine-associated lineage. In addition to the bovine-associated lineage-specific genes, including fimbriae, capsule, and nutrition utilization genes, specific virulence gene communities have been accumulated in stx- and LEE-positive strains, respectively, with notable overlaps of community members. Functional associations of these genes probably confer benefits to these E. coli strains in inhabiting and/or adapting to the bovine intestinal environment and drive their evolution to highly virulent human pathogens under the bovine-adapted genetic background. Our data highlight the importance of large-scale genome sequencing of animal strains in the studies of zoonotic pathogens.

Clinical Characteristics of Severe Refractory Asthma Associated with the Effectiveness of Bronchial Thermoplasty.

We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting ß2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p<0.05). The %FEV1, FeNO, IgE, and Eosi did not change significantly between baseline and 6 months post-BT. No severe complications were reported. BT was effective for non-allergic and non-eosinophilic in 3 patients, and allergic or eosinophilic in 4 patients. Their AQLQ improved by > 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab.

Success of Crizotinib Combined with Whole-Brain Radiotherapy for Brain Metastases in a Patient with Anaplastic Lymphoma Kinase Rearrangement-Positive Non-Small-Cell Lung Cancer.

Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug. Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib. Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases. Additionally, we focused on the mechanism involved by examining the plasma and cerebrospinal fluid concentrations of crizotinib in the present case.

Low Variability in Peak Expiratory Flow Predicts Successful Inhaled Corticosteroid Step-Down in Adults with Asthma.

BACKGROUND: The prognosis for patients beyond 1 year after reduction of their inhaled corticosteroid (ICS) dose remains unknown. Predictive factors that can be evaluated before the initiation of asthma treatment or at ICS dose reduction are unknown. METHODS: We prospectively studied 223 patients in 6 hospitals in the National Hospital Organization of Japan during the 36 months after 50% reduction of their daily ICS dose. All patients recorded their morning and evening peak expiratory flows (PEFs) in their diaries. Lung function, bronchial hyperresponsiveness, fractional nitric oxide levels, number of eosinophils in sputum, and serum IgE levels were measured in most patients. Serum levels of IL-10, IL-33, and thymic stromal lymphopoietin before ICS dose reduction were measured in all patients. RESULTS: During the 36-month study period, asthma control was retained in 127 (59.6%) of the 213 enrolled patients who underwent ICS dose reduction. Multivariate logistic regression analysis revealed that, at the initiation of dose reduction, the factors most predictive of maintenance of asthma control after ICS dose reduction were a low serum IL-33 level (P < .01), low PEF variability over 1 week (P = .014), childhood onset of asthma (at age <10 years) (P = .03), and high serum IL-10 level (P = .035). CONCLUSIONS: We demonstrated that low PEF variability over 1 week, high serum IL-10 level, and low serum IL-33 concentration were useful factors for predicting that an adult's asthma will remain in control for months to years after a 50% reduction in the daily ICS dose.

Usefulness of Bronchial Thermoplasty for Patients with a Deteriorating Lung Function.

Bronchial thermoplasty is a novel procedure for patients with severe asthma showing a stable lung function. We herein report two cases with a deteriorating lung function. The lung function tended to improve in one case, while the other case discontinued mepolizumab medication after the procedure. Treatment was performed safely under general anesthesia in both cases. The use of bronchial thermoplasty may therefore be useful for the treatment of patients with a deteriorating lung function.

Multiple Mucosa-associated Lymphoid Tissue Lymphoma of the Trachea.

Mucosa-associated lymphoid tissue lymphoma is a common type of primary pulmonary carcinoma, but the presence of polypoid nodules is extremely rare. We herein report two cases with multiple nodules in the trachea. One case involved polypoid nodules and airway stenosis mimicking asthma; the other case had concurrent nontuberculous mycobacterial infection. The diagnosis of both cases was confirmed by bronchoscopy. The two cases were sensitive to radiotherapy and chemotherapy, respectively.

Bronchoscopic diagnosis of peripheral pulmonary lung cancer employing sedation with fentanyl and midazolam.

BACKGROUND: Sedation with fentanyl and midazolam during bronchoscopic examination is commonly employed by pulmonary physicians in the USA and Europe. We assessed the efficacy of such sedation in the bronchoscopic diagnosis of peripheral lung cancer. METHODS: We retrospectively evaluated data from 102 patients who underwent transbronchial biopsies (TBB) for diagnosis of peripheral lung cancer. Bronchoscopies with and without fentanyl were performed in 61 (group A) and 41 (group B) patients, respectively. Midazolam was administered to all patients. Medical records were retrieved, and between-group comparisons were made using unpaired Student's t-tests. RESULTS: The mean fentanyl dose was 49.5 µg (range: 10-100 µg), and midazolam doses in groups A and B were 4.29mg (range: 1-14mg) and 5.54mg (range: 1-12mg), respectively. Diagnostic histological specimens were obtained from 75.4% and 65.8% of group A and B patients, respectively (P = 0.30). The diagnostic sensitivities for lung cancer, via at least one of TBB, cytological brushing, or bronchial washing, in groups A and B were 88.5% and 70.4%, respectively (P = 0.035). Moreover, lesion diagnostic sensitivities, via at least one of TBB, cytological brushing, and bronchial washing, in groups A and B were 98.1% and 68.0%, respectively (P = 0.01). CONCLUSION: Fentanyl and midazolam sedation during bronchoscopy facilitated the diagnosis of peripheral pulmonary lung cancers.

Improved porcine model for Shiga toxin-producing Escherichia coli infection by deprivation of colostrum feeding in newborn piglets.

Porcine edema disease (ED) is a toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC). ED occurs most frequently during the weaning period and is manifested as emaciation associated with high mortality. In our experimental infection with a specific STEC strain, we failed to cause the suppression of weight gain in piglets, which is a typical symptom of ED, in two consecutive experiments. Therefore, we examined the effects of deprivation of colostrum on the sensitivity of newborn piglets to STEC infection. Neonatal pigs were categorized into two groups: one fed artificial milk instead of colostrum in the first 24 h after birth and then returned to the care of their mother, the other breastfed by a surrogate mother until weaning. The oral challenge with 1011  colony-forming units of virulent STEC strain on days 25, 26 and 27 caused suppression of weight gain and other ED symptoms in both groups, suggesting that colostrum deprivation from piglets was effective in enhancing susceptibility to STEC. Two successive STEC infection experiments using colostrum-deprived piglets reproduced this result, leading us to conclude that this improved ED piglet model is more sensitive to STEC infection than the previously established models.

Clinical impact of complete revascularization in elderly patients with multi-vessel coronary artery disease undergoing percutaneous coronary intervention: A sub-analysis of the SHINANO registry.

BACKGROUND: Prior reports have revealed that complete revascularization (CR) by percutaneous coronary intervention (PCI) decreased ischemic events. However, little is known about the efficacy of CR using PCI in elderly patients with multi-vessel coronary artery disease (CAD). We evaluated the 1-year effectiveness of CR-PCI in elderly patients (≥75years old) with multi-vessel CAD. METHODS: The SHINANO Registry, a prospective, observational, multi-center, all-comer cohort study, has enrolled 1923 patients. From this registry, we recruited 322 elderly patients with multi-vessel CAD. The primary endpoint was major adverse cardiovascular events ([MACE]: all-cause mortality, myocardial infarction, and stroke). RESULTS: Of the 322 elderly patients with multi-vessel CAD, 165 (51.2%) received CR and 157 (48.8%) received incomplete revascularization (ICR). MACE occurred in 44 (13.7%) patients. The incidence of MACE by survival analysis was significantly lower in the CR group than in the ICR group (7.4% vs. 21.1%, p<0.001). On multivariable Cox proportional hazards analysis of age, sex, and acute coronary syndrome (ACS), ACS and CR were independent predictors of MACE (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.29-4.80; p=0.007, HR, 0.40; 95% CI, 0.20-0.77; p=0.007, respectively). In propensity score matching of age, sex, previous heart failure, previous intracranial bleeding, ACS, and body mass index, the MACE rate was significantly lower in the CR group than in the ICR group (7.2% vs. 18.4%, p=0.015). CONCLUSIONS: Even in elderly patients over 75years old with multi-vessel CAD, CR-PCI appears to suppress mid-term ischemic events.

Comparison of mid-term outcomes between patients with and without atrial fibrillation undergoing coronary stenting in the second-generation drug-eluting stent era: from the SHINANO registry.

Little is known about the mid-term outcomes of patients with atrial fibrillation (AF) who undergo coronary stenting in the second-generation drug-eluting stent (DES) era. We evaluated the 1-year outcomes of AF patients undergoing percutaneous coronary intervention (PCI) with second-generation DES. This retrospective cohort analysis used integrated data from the SHINANO registry, a prospective observational multicenter cohort study, which enrolled 1923 consecutive patients undergoing PCI for any coronary artery disease. We retrospectively recruited 917 of these patients (mean age, 71.3 ± 10.0 years; male, 77 %) who received PCI with 2nd generation DES. The primary endpoint was net adverse clinical events (NACE: cardiac death, stroke, MI, stent thrombosis, and major bleeding) at 1 year. The secondary endpoints were major adverse cardiovascular events (MACE: cardiac death, stroke, and MI), stroke, MI, and major bleeding at 1 year. One-year follow-up was completed in 871 (94.9 %) patients, of whom 85 had AF. The incidence of NACE (15.4 vs. 7.3 %, P = 0.008), MACE (10.6 vs. 5.4 %, P = 0.047), and major bleeding (6.0 vs. 2.3 %, P = 0.049) were all significantly higher in AF compared to non-AF patients. On multivariate analysis, AF was an independent predictor of NACE (HR 2.32, 95 % CI 1.24-4.34, P = 0.008). In the second-generation DES era, patients with AF undergoing PCI still have a poorer prognosis, with more thrombotic and bleeding events, than those without AF. More attention should be paid to the thrombotic and bleeding risk in AF patients undergoing PCI.

Efficacy and Safety of Percutaneous Coronary Intervention for Elderly Patients in the Second-Generation Drug-Eluting Stent Era: The SHINANO Registry.

BACKGROUND: We evaluated the 1-year outcomes of percutaneous coronary intervention (PCI) for elderly patients (aged ≥ 80 years) in the second-generation drug-eluting stent (DES) era. METHODS AND RESULTS: Between August 2012 and July 2013, 1923 consecutive patients (mean age, 71 ± 11 years; ≥80 years, 23%; men, 77%) who underwent 2250 elective/urgent PCI procedures were enrolled in the Shinshu Prospective Multicenter Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention registry. The primary end point was major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, and stroke) at 1 year. The 1-year incidence of MACEs, cardiac death, and stroke was significantly higher in elderly patients than in nonelderly patients (12.4% vs 5.3%, P < .0001; 7.8% vs 2.2%, P < .0001; and 2.8% vs 1.3%, P = .033, respectively). However, no significant difference in elective PCI procedures was detected. In elderly patients, the incidence of cardiac death and target lesion revascularization was significantly lower for DES than for non-DES (2.7% vs 10.5%, P = .0001 and 4.1% vs 8.6%, P = .029, respectively). CONCLUSION: Although elderly patients had a significantly poorer prognosis than younger patients, the adverse events rate was comparable in those patients who underwent elective PCI in the second-generation DES era.

Prediction of 1-year clinical outcomes using the SYNTAX score in patients with prior heart failure undergoing percutaneous coronary intervention: sub-analysis of the SHINANO registry.

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.

Relationship between morphological characteristics of hyoid bone and mandible in Japanese cadavers using three-dimensional computed tomography.

The aim of this study is to obtain a quantitative anatomical description of the hyoid bone and mandible using three-dimensional computed tomography. Hyoid bones were obtained from a total of 101 cadavers varying in age from 67 to 102 years. The percentage of symmetrical U-type and asymmetrical-type hyoid bones was low compared with symmetrical V type (14.9, 15.8, and 69.3 %, respectively), and no significant sex difference was observed. We found bilateral nonfusion in cadavers of advanced age at a rate of 22.7 % and bilateral complete fusion at a rate of 51.5 %. There were significant differences in metric variables (length and width) between males and females, but no significant differences in width among the different fusion types. There was no significant interaction effect of sex and degree of fusion. Strong significant associations were observed between size (length and width) of the hyoid bone and mandible in the nonfusion group, while the complete fusion group revealed a moderate correlation. We also investigated the hypothesis that the junction between the hyoid body and greater horn plays an important role in the movement of bones that have not yet ossified. However, no statistical difference was observed in the width between the two greater horns. The degree of fusion of the greater horn with the hyoid body may also affect relations of interdependencies between the hyoid bone and mandible, an important component to consider when assessing risk factors in the development of masticatory and swallowing function.

Predictive Value of Combining the Ankle-Brachial Index and SYNTAX Score for the Prediction of Outcome After Percutaneous Coronary Intervention (from the SHINANO Registry).

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.

Lean body mass index prognostic value for cardiovascular events in patients with coronary artery disease.

OBJECTIVE: Little is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship. METHODS: The SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m2; LBMI 18.3±1.8 kg/m2; FMI 5.4±2.2 kg/m2). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year. RESULTS: Over a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan-Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4-22.2 kg/m2) (p=0.002) and lower LBMI values (11.6-17.6 kg/m2) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30). CONCLUSIONS: Lower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI. CLINICAL TRIAL REGISTRATION: UMIN-ID; 000010070.

Risk stratification using the CHA2DS2-VASc score in patients with coronary heart disease undergoing percutaneous coronary intervention; sub-analysis of SHINANO registry.

BACKGROUND: CHADS2 or CHA2DS2-VASc score is used for prediction of stroke in patients with atrial fibrillation (AF). Recently, CHADS2 score is reported to have prognostic value in acute coronary syndrome without AF. However, clinical validation of CHA2DS2-VASc score for prognostic stratification in coronary heart disease (CHD) without AF remains uncertain. In this study, we evaluate whether CHA2DS2-VASc score could predict clinical outcome in CHD without known AF. METHODS: SHINANO registry was a prospective, observational, multicenter cohort study, enrolling 1923 consecutive patients with CHD from August 2012 to July 2013. Two hundred nine patients were excluded because of known AF. We calculated CHA2DS2-VASc score in the remaining 1714 patients (mean age 70 ± 11 years, 23% female) without known AF. To assess the clinical validation of CHA2DS2-VASc score, we divided patients into 3 groups according to the tertiles (score 0-2, 3-4, and ≥ 5). The primary endpoint was MACE including death, nonfatal myocardial infarction, and ischemic stroke at 1 year. RESULTS: One-year follow-up was completed in 1632 patients (95.2%). Cumulative incidence of MACE was 139 cases. In Kaplan-Meier analysis, incidence of MACE was significantly higher in patients with CHA2DS2-VASc score ≥ 5 compared to 3-4 and 0-2 (14.6% vs. 6.8% vs. 5.3%, p < 0.001). In multivariate Cox-regression analysis, CHA2DS2-VASc score was an independent predictor for MACE (hazard ratio 1.26, 95% confidence interval 1.15-1.39p < 0.001). CONCLUSIONS: This study demonstrated that CHA2DS2-VASc score could provide prognostic information in CHD without known AF.