Incidence of elevated creatine phosphokinase between daptomycin alone and concomitant daptomycin and statins: A systematic review and meta-analysis.

AIMS: The present systematic review and meta-analysis evaluated the incidence of elevated creatine phosphokinase (CPK) levels between daptomycin alone and concomitant daptomycin and statin use. METHODS: We searched the PubMed, Web of Sciences, Cochrane Library and ClinicalTrials.gov databases. We analysed the incidence of elevated CPK between daptomycin alone and concomitant daptomycin and statins among studies defining CPK elevation as levels ≥ the upper limit of normal (ULN) or ≥5× ULN. We also analysed the incidence of rhabdomyolysis between the groups. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) based on the included studies. RESULTS: Comparing CPK elevation defined as CPK levels ≥ULN, a significantly higher incidence of CPK elevation was observed with concomitant daptomycin and statin use than with daptomycin alone (OR = 2.55, 95% CI 1.78-3.64, P < .00001, I2  = 0%). Likewise, when CPK elevation was defined as CPK levels ≥5× ULN, a significantly higher incidence of CPK elevation was detected with concomitant daptomycin and statin use than with daptomycin alone (OR = 1.89, 95% CI 1.06-3.35, P = .03, I2  = 48%). The incidence of rhabdomyolysis was significantly higher following concomitant daptomycin and statin use than with daptomycin alone (OR = 11.60, 95% CI 1.81-74.37, P = .01, I2  = 0%). CONCLUSION: The combined use of daptomycin and statins were significant risk factors for the incidence of CPK elevation defined as levels ≥ULN or ≥5× ULN and rhabdomyolysis.

Support for fungal infection treatment mediated by pharmacist-led antifungal stewardship activities.

OBJECTIVE: At the Yokohama General Hospital, pharmacist-led antimicrobial stewardship programs (ASP) including antifungal stewardship programs (AFP) were started in 2012. To investigate the efficacy of the programs, we compared several parameters that are recommended for the measurement of ASP in Japan based on pre- and post-AFP activities. PATIENTS AND METHODS: The subjects were inpatients who developed candidemia between April 2008 and March 2016. They were divided into two groups: pre-AFP (April 2008 until March 2012) and post-AFP (April 2012 until March 2016). The results were compared between the two groups. RESULTS: The cumulative optimal antifungal drug usage rate, as a process parameter, significantly increased in the post-AFP group (p = 0.025). Furthermore, the days of therapy of antifungal drugs in the pre- and post-AFP groups was median 6.0 (interquartile range [IQR] 0.3-15.7) and median 3.4 (IQR 1.9-3.4) per 1,000 patient-days, respectively; there was a significant decrease in the post-AFP group (p < 0.001). Expenditure on antifungal drugs, as an outcome parameter, in the pre- and post-AFP groups was 9390.5 ± 5687.1 and 5930.8 ± 4687.0 US dollars, respectively; there was a significant decrease in the post-AFP group (p = 0.002). CONCLUSIONS: These results suggest that pharmacist-led antifungal stewardship activities improve both outcome and process parameters.

Associations of coronary plaque characteristics by integrated backscatter intravascular ultrasound with detectability of vessel external elastic lamina using optical frequency domain imaging in human coronary arteries: A sub-analysis of the MISTIC-1 trial.

OBJECTIVES: We sought to examine associations between plaque characteristics by intravascular ultrasound (IVUS) and detectability of external elastic lamina (EEL) by optical frequency domain imaging (OFDI) in human coronary arteries. BACKGROUND: It is often challenging to detect EEL which represents vessel size by light-based imaging modalities due to light intensity attenuation through atherosclerotic plaque. METHODS: IVUS and OFDI prior to stent implantation were sequentially investigated per protocol. We identified corresponding cross-sections by minimum lumen area (MLA) or just distally to side branches as anatomical landmarks. Plaque characterization was determined by integrated backscatter IVUS analysis. We categorized detectable EEL arc by OFDI into four groups: 0≤ and <1 quadrant (group 1), 1≤ and <2 quadrants (group 2), 2≤ and <3 quadrants (group 3), or 3≤ and <4 quadrants (group 4). RESULTS: We prospectively studied 103 vessels in 93 patients with stable coronary artery disease. Corresponding 711 cross-sections were analyzed. Cross-sections with detectable EEL arc <2 quadrants (group 1 or 2) were observed in 86.1% of MLA sites but only in 29.3% of non-MLA sites (p < .05). Percentage plaque area (%PA) appeared to be the strongest predictor to detect EEL arc <2 quadrants with the cut-off of 60.3% (AUC 0.90; sensitivity 79.8%, specificity 85.5%). Lipid pool and calcification remained statistically significant in predicting detectable EEL arc <2 quadrants after adjustment with %PA. CONCLUSIONS: Presence of large plaque burden, lipid pool, and calcification significantly predicts the detectability of EEL by OFDI assessment. Locations with detectable EEL arc <2 quadrants should thus be avoided for optimal stent landing zone.

Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.

OBJECTIVES: The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS: The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). RESULTS: Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. CONCLUSIONS: Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.

Prescription patterns of oral anticoagulants for patients with non-valvular atrial fibrillation: experience at a Japanese single institution.

New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

Urinary neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) events. Recently, elevated neutrophil gelatinase-associated lipocalin (NGAL) levels have been reported in patients with heart failure, coronary heart disease, or stroke. Our aim was to assess urinary NGAL as a predictor of CV events in patients with CKD. This was a prospective observational cohort study of 404 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, hospitalization for worsening heart failure, stroke and dissection of aorta. During a mean follow-up period of 33 months, 77 CV events (19.1 %) occurred. After adjustment for gender, age, diabetes, previous cardiovascular disease, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate, hemoglobin, and high-sensitivity C-reactive protein, patients with the other quartiles of urinary NGAL had significantly higher risk of CV events compared with patients with the lowest quartile (hazard ratio (HR) 2.81, 95 % confidence interval (CI) 1.01-7.81, P = 0.047 for Q2, HR 3.31, 95 % CI 1.22-9.00, P = 0.019 for Q3, and HR 3.27, 95 % CI 1.15-9.29, P = 0.026 for Q4). Regarding the combination of urinary NGAL with UACR, we also stratified patients into four groups according to whether the level of each marker was above or below the median (61.8 µg per gram creatinine (gCr) for NGAL and 351.1 mg/gCr for UACR). Four-year CV event-free survival rates were 89.2, 79.6, 71.8, and 51.5 % in order for the four respective groups (P < 0.0001). Elevated urinary NGAL was able to predict future CV events in CKD patients, and had incremental predictive value with elevated UACR.

Clinical Characteristics and Long-Term Outcomes of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan-Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death.

Kidneys procured by donation after cardiac death (DCD) may increase the donor pool but are associated with high incidence of delayed graft function (DGF). Urinary liver-type fatty acid-binding protein (L-FABP) level is an early biomarker of renal injury after kidney transplantation (KTx); however, its utility is limited in DGF cases owing to urine sample unavailability. We examined whether serum L-FABP level predicts functional recovery of transplanted DCD kidneys. Consecutive patients undergoing KTx from living related donors (LD), brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels were measured from samples collected before and after KTx. Serum L-FABP decreased rapidly in patients with immediate function, slowly in DGF patients, and somewhat increased in DGF patients requiring hemodialysis (HD) for >1 wk. Receiver-operating characteristic curve analysis demonstrated that DGF was predicted with 84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0 ng/mL on post-operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7 d was predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD KTx.

Adding coronary computed tomography angiography to invasive coronary angiography improves prediction of cardiac events.

BACKGROUND: The additive value of plaque characteristics determined by computed tomography angiography (CTA) in patients undergoing invasive coronary angiography (ICA) has not been established. METHODS AND RESULTS: We studied 676 patients undergoing ICA and CTA within 3 months. The luminal diameter narrowing based on ICA and the presence of high risk plaque (HRP) based on CTA were assessed in all coronary artery segments except for those after or before scheduled treatment. We followed their cardiac events including cardiac death, acute coronary syndrome (ACS), and revascularization for de novo lesions ≥3 months after ICA. The incidence of coronary events was higher in the segments including >25% luminal narrowing than in those without (2.94% vs. 0.31%, P<0.0001), and higher in the segments containing HRP than in those without (12.6 vs. 0.46%, P<0.0001). Greater than 25% residual luminal narrowing and the presence of HRP were identified as independent predictors of cardiac events after risk adjustment for age, gender, and history of ACS (hazard ratio [HR], 3.22; 95% confidence interval [CI]: 1.29-10.76; P=0.0092, HR, 2.64; 95% CI: 1.59-4.35; P=0.0002, respectively). Adding the presence of HRP to a model including age, gender, ACS history, and >25% residual stenosis improved the prediction of cardiac events. CONCLUSIONS: Assessment of coronary plaque characteristics on CTA improves the prediction of cardiac events in patients undergoing ICA.

Characteristics of plaque progression detected by serial coronary computed tomography angiography.

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics.

Febuxostat (Feburic tablet) in the management of hyperuricemia in a general practice cohort of Japanese patients with a high prevalence of cardiovascular problems.

Hyperuricemia is increasing in prevalence and this is paralleled by an increased incidence of acute gout. In addition, there is growing evidence of an association between high serum levels of uric acid (sUA) and cardiovascular disease (CVD). In this preliminary report, we present 12-16 week results from a multicenter, general practice study in which we evaluated the usefulness of febuxostat in a cohort of untreated patients with hyperuricemia with a high prevalence of CVD. Febuxostat titrated from 10 mg/day up to 40 mg/day resulted in statistically significant and clinically relevant reductions in sUA after 12-16 weeks. A "responder" level of 6.0 mg/dL or lower was achieved in 95 of 100 (95%) patients. Significant reductions in sUA were achieved regardless of the presence/absence of coexisting diseases (e.g. CVD, renal insufficiency, diabetes and obesity) or the class of antihypertensive agent being used by the patient. No serious adverse reactions were noted with febuxostat. Although allopurinol has been used generally for hyperuricemia/gout, it is excreted fully via the kidneys, restricting its use in patients with reduced renal function, and its three-times-daily administration leads to poor adherence. Based on the results of this study, febuxostat may provide an easier option than allopurinol for clinicians specializing in CVDs.

Poly(ester imide)s with Low Linear Coefficients of Thermal Expansion and Low Water Uptake (VII): A Strategy to Achieve Ultra-Low Dissipation Factors at 10 GHz.

In this study, a series of ester-linked tetracarboxylic dianhydrides (TCDAs) with 2,6-naphthalene-containing longitudinally extended structures consisting of different numbers of aromatic rings (NAr = 6-8) was synthesized to obtain novel modified polyimides, poly(ester imide)s (PEsIs). These TCDAs were fully compatible with the conventional manufacturing processes of conventional polyimide (PI) systems. As an example, the PEsI film obtained from the ester-linked TCDA (NAr = 8) and an ester-linked diamine achieved unprecedented outstanding dielectric properties without the support of fluorinated monomers, specifically an ultra-low dissipation factor (tan δ) of 0.00128 at a frequency of 10 GHz (50% RH and 23 °C), in addition to an extremely high glass transition temperature (Tg) of 365 °C, extremely low linear coefficient of thermal expansion (CTE) of 6.8 ppm K-1, suppressed water uptake (0.24%), requisite film ductility, and a low haze. Consequently, certain PEsI films developed in this study are promising candidates for heat-resistant dielectric substrates for use in 5G-compatible high-speed flexible printed circuit boards (FPCs). The chemical and physical factors denominating tan δ are also discussed.

Association of serum carotenoid levels with N-terminal pro-brain-type natriuretic peptide: a cross-sectional study in Japan.

BACKGROUND: Several epidemiologic studies have reported an inverse association between serum levels of carotenoids and cardiovascular disease risk. However, no studies have reported an association between serum carotenoids and N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in the general population. METHODS: In this cross-sectional study, we investigated whether serum carotenoids were associated with serum NT-proBNP in 1056 Japanese subjects (390 men, 666 women) who attended a health examination. Serum levels of carotenoids were separately determined by high-performance liquid chromatography. Serum NT-proBNP level was measured by electrochemiluminescence immunoassay. RESULTS: Serum NT-proBNP was elevated (≥55 pg/ml) in 31.8% of men and 48.2% of women. Multivariate logistic regression analyses adjusted for confounding factors showed a significant association between the highest quartile of serum α-carotene and elevated NT-proBNP in men (odds ratio [OR] = 0.40, 95% CI = 0.19-0.82, P for trend = 0.005) and women (OR = 0.62, 95% CI = 0.39-0.99, P for trend = 0.047). In women, moreover, elevated serum NT-proBNP was significantly associated with serum canthaxanthin (OR = 0.57, 95% CI = 0.36-0.90 for highest quartile, P for trend = 0.026) and ß-cryptoxanthin (OR = 0.53, 95% CI = 0.32-0.85 for highest quartile, P for trend = 0.026), after adjusting for potential confounders. CONCLUSIONS: Higher levels of serum carotenoids were associated with lower risk of elevated serum NT-proBNP levels after adjusting for possible confounders, which suggests that a diet rich in carotenoids could help prevent cardiac overload in the Japanese population.

Prognostic value of highly sensitive troponin T on cardiac events in patients with chronic kidney disease not on dialysis.

Serum troponin T levels using a highly sensitive assay (hsTnT) in patients with chronic kidney disease (CKD) not on dialysis have not been examined. The aim of this prospective cohort study was to investigate the association of hsTnT with cardiac events in ambulatory CKD patients not on dialysis. The serum hsTnT level was measured in 442 ambulatory CKD patients not on dialysis whose estimated glomerular filtration rate was <60 ml/min/1.73 m(2). Patients were divided into quartiles according to hsTnT levels, and were followed up for 3 years. Cardiac events were defined as a cardiac death, acute myocardial infarction, unstable angina pectoris that required emergency coronary revascularization, or hospitalization for worsening heart failure. During the follow-up period (median 22 months), 63 cardiac events occurred. Kaplan-Meier incidence rates of cardiac events for 3 years were 0.88 %, 11.5 %, 19.0 %, and 41.4 % among quartiles of hsTnT levels (P < 0.0001). After adjusting for other confounders, elevated hsTnT level was an independent predictor for cardiac events (hazard ratio 6.18, 95 % confidence interval 1.38-27.7, P = 0.0080 for highest quartile vs lowest quartile). In addition, C-index for receiver-operating characteristic curves for cardiac events was greater in an established risks plus hsTnT model than in the established risk alone model (0.857 vs 0.844, P = 0.026). Using a highly sensitive assay, serum hsTnT level was shown to be an independent predictor of cardiac events and a promising risk stratification tool in patients with CKD not on dialysis.

Low dose of hydrochlorothiazide, in combination with angiotensin receptor blocker, reduces blood pressure effectively without adverse effect on glucose and lipid profiles.

Previous studies have shown highly effective lowering of blood pressure with thiazide diuretics in combination with angiotensin receptor blockers. However, thiazide diuretics may cause the development of diabetes and abnormal lipid metabolism. Little is known as to whether dysmetabolic potential of thiazide diuretics could be neutralized when adding angiotensin receptor blockers. This study consisted of 26 patients with essential hypertension. Patients were randomized to 24 weeks of treatment with either candesartan, 12 mg monotherapy (n = 13, group A), or hydrochlorothiazide (HCTZ), 6.25 mg in combination with candesartan, 8 mg (n = 13, group B). Before and after treatment, we assessed glucose and lipid profiles including adiponectin, resistin, and active glucagon-like peptide-1 (GLP-1) levels. At baseline, there were no differences in age, body mass index, systolic blood pressure (SBP), and diastolic blood pressure (DBP), as well as plasma levels of hemoglobin A1c, insulin, low-density lipoprotein cholesterol, triglycerides, adiponectin, resistin, and active GLP-1 between the two groups. There were significant reductions in SBP (from 152 ± 10 mmHg at baseline to 134 ± 12 mmHg after treatment) and DBP (from 84 ± 5 mmHg at baseline to 71 ± 8 mmHg after treatment) in group A. There were also significant reductions in SBP (from 148 ± 10 at baseline to 128 ± 7 mmHg after treatment) and DBP (from 90 ± 9 at baseline to 74 ± 12 mmHg after treatment) in group B. There were no differences in reduction of SBP or DBP after 24 weeks of treatment between the two groups. There were no changes of the glucose and lipid profiles, including adiponectin, resistin, insulin, and active GLP-1 levels after 24 weeks of treatment in both groups. A low dose of HCTZ in combination with candesartan reduces blood pressure effectively without adverse effects on the glucose and lipid profiles. Therefore, the combination of thiazide diuretics and angiotensin receptor blockers could assist patients in achieving long-term control of blood pressure with good tolerability.

Colorless Polyimides Derived from 5,5'-bis(2,3-norbornanedicarboxylic anhydride): Strategies to Reduce the Linear Coefficients of Thermal Expansion and Improve the Film Toughness.

In this paper, novel colorless polyimides (PIs) derived from 5,5'-bis(2,3-norbornanedicarboxylic anhydride) (BNBDA) were presented. The results of single-crystal X-ray structural analysis using a BNBDA-based model compound suggested that it had a unique steric structure with high structural linearity. Therefore, BNBDA is expected to afford new colorless PI films with an extremely high glass transition temperature (Tg) and a low linear coefficient of thermal expansion (CTE) when combined with aromatic diamines with rigid and linear structures (typically, 2,2'-bis(trifluoromethyl)benzidine (TFMB)). However, the polyaddition of BNBDA and TFMB did not form a PI precursor with a sufficiently high molecular weight; consequently, the formation of a flexible, free-standing PI film via the two-step process was inhibited because of its brittleness. One-pot polycondensation was also unsuccessful in this system because of precipitation during the reaction, probably owing to the poor solubility of the initially yielded BNBDA/TFMB imide oligomers. The combinations of (1) the structural modification of the BNBDA/TFMB system, (2) the application of a modified one-pot process, in which the conditions of the temperature-rising profile, solvents, azeotropic agent, catalysts, and reactor were refined, and (3) the optimization of the film preparation conditions overcame the trade-off between low CTE and high film toughness and afforded unprecedented PI films with well-balanced properties, simultaneously achieving excellent optical transparency, extremely high Tg, sufficiently high thermal stability, low CTE, high toughness, relatively low water uptake, and excellent solution processability.

Combination of brain natriuretic peptide and urinary albumin as a predictor of cardiovascular-renal events in outpatients with chronic kidney disease.

Objectives: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular-renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. Methods: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular-renal events. Results: During the median follow-up period of 109 months, 221 patients developed cardiovascular-renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular-renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81-3.72) and 2.27 (95% CI, 1.82-2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23-29.42) of cardiovascular-renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p<0.0001), and integrated discrimination improvement (0.071, p<0.0001) more than each of them alone. Conclusions: This is the first report to demonstrate that the combination of BNP and urinary albumin can stratify and improve the predictability of long-term cardiovascular-renal events in CKD patients.

Stiffness as measured with strain elastography is a prognostic factor for pT1/T2 tongue squamous cell carcinoma with muscle-layer invasion.

OBJECTIVE: The objective was to evaluate stiffness as a prognostic factor for tongue squamous cell carcinoma (TSCC). STUDY DESIGN: This retrospective study included 55 patients with pathologic stage pT1 or T2 TSCC with muscle-layer invasion who underwent preoperative strain elastography of the tongue, followed by surgery, as the primary treatment modality at our cancer center. The stiffness of TSCC was semi-quantified as the ratio of the strain value of a non-tumor site to the strain value of the tumor site (strain ratio [SR]) using ultrasound strain elastography findings. RESULTS: SR cutoff values that maximized the significance of the difference for prognosis of delayed cervical lymph node metastasis (DCLNM) and overall survival (OS) were 7.10 and 7.49, respectively. In univariate analysis, SR, age, depth of invasion, pT stage, and perineural invasion were significant risk factors for DCLNM, whereas SR, sex, and DCLNM were identified as having an association with OS. In multivariate analysis, SR was a significant risk factor for DCLNM (hazard ratio [HR] = 3.102; P = .021) and a non-significant but relevant risk factor for OS (HR = 8.774; P = .073). Age also had an association with OS (HR = 0.382; 95% CI 0.127-1.152; P = .088). CONCLUSION: Tongue stiffness is a prognostic factor in patients with pT1/T2 TSCC with muscle-layer invasion. SR values >7.10 indicate a poor prognosis, thereby warranting a strict follow-up regimen in these cases.

Coronary plaque characteristics in patients with mild chronic kidney disease. Analysis by 320-row area detector computed tomography.

BACKGROUND: The differences in the coronary plaque characteristics between patients with mild chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 30-59 ml·min(-1) · 1.73 m(-2)) and those without CKD (eGFR ≥60) by 320-row area detector computed tomography (CT) have not been studied. METHODS AND RESULTS: We enrolled 487 patients undergoing coronary CT angiography with suspected stable coronary artery disease (mean age: 66.6±10.8 years, 131 with mild CKD) and analyzed 6,352 segments. All coronary plaques were characterized for the presence of vessel remodeling, plaque consistency and the disposition of coronary calcification, and a plaque with positive vessel remodeling and/or low-attenuation was defined as high risk. The number of diseased segments per patient was higher in mild CKD patients than in those without CKD (4.61±3.83 vs. 2.95±3.11, P<0.0001). The prevalence of severe stenosis (≥70% luminal diameter) was significantly higher in cases of mild CKD than in no CKD (35.1% vs. 19.4%, P=0.0003), but there was no significant difference in the prevalence of high-risk plaque (13.0% vs. 9.8%, P=0.3189). CONCLUSIONS: The severity of coronary artery stenosis was higher in the patients with mild CKD, though there was no significant difference in the prevalence of high-risk plaque. We suggest that the high risk of coronary events in patients with CKD is related to the severity of stenosis rather than to the characteristics of plaque.

Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy.

AIMS: Pathological and clinical optical coherence tomography (OCT) studies have indicated that acute coronary syndrome (ACS) lesions have either ruptured fibrous caps (RFC-ACS) or intact fibrous caps (IFC-ACS). Although computed tomographic (CT) angiographic characteristics of RFC-ACS include low-attenuation plaques and positive plaque remodelling, features associated with IFC-ACS have not been previously described. The aim of this study was to assess the CT characteristics of IFC-ACS lesions. METHODS AND RESULTS: Seventy-four patients with ACS/stable angina consented to multimodality imaging, of which 66 underwent CT angiography. Of these, 57 culprit lesions in 57 patients were evaluated with sufficient image quality from all four of OCT, angioscopy, intravascular ultrasound, and CT angiography. Intraluminal thrombus was assessed by OCT/angioscopy, and culprit lesions further classified by OCT-based demonstration of fibrous cap integrity. Of 35 culprit lesions with ACS, OCT revealed IFC with thrombus in 10 (29%) and RFC in the remaining 25 (71%); all 22 lesions with stable angina had intact fibrous caps. Fibrous caps were significantly thinner in RFC-ACS than IFC-ACS and stable angina (45 ± 12, 131 ± 57, and 321 ± 146 µm, respectively; P = 0.001). CT angiography revealed that low-attenuation plaques were more frequently observed in RFC-ACS than IFC-ACS and stable angina (88, 40, and 18%; P = 0.001) lesions. Similarly, positive remodelling was more predominantly seen in RFC-ACS than IFC-ACS and stable angina (96, 20, and 14%; P = 0.001). However, none of the specific CT angiography features clearly distinguished IFC-ACS from stable lesions. CONCLUSION: In contrast to the situation with RFC-ACS, distinct culprit lesion characteristics associated with non-rupture-related mechanisms are not identified by CT angiography. It will therefore not be possible to differentiate plaques likely to develop IFC-ACS from stable plaques.