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Background: Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications. Methods and Results: We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years). Conclusions: Women are at higher risk than men for post-procedural complications after PCI, regardless of age. [ABSTRACT FROM AUTHOR]

SUZUKI, M., et al.: Role of Vagal Control in Vasovagal Syncope. The vasovagal reaction is thought to be caused by sympathetic withdrawal and vagal augmentation. While measurements of muscle sympathetic nerve activity support sympathetic withdrawal in tilt induced syncope, the results of previous attempts to quantify vagal control using spectral analyses of heart rate variability (HRV) remain controversial. The sampling period used in the HRV studies is related to the discordant results. In the present study, HRV was computed every second using wavelet transformation to clarify the role of vagal control in tilt induced syncope during the 80-degree head-up tilt test (positive: 10 patients with vasovagal syncope; negative: 10 patients with vasovagal syncope, and 10 control subjects). Autonomic modulations were assessed using the absolute power of the low frequency (LF) (0.04–0.15 Hz) and high frequency (HF) (0.15–2.00 Hz) oscillatory components of R-R variability. Although the LF did not change during the tilt procedure, a decrease in the systolic arterial pressure (SAP) and increases in the R-R interval and HF were observed for the last 30 seconds before the tilt induced syncope in the tilt-positive group. Analyzing the hemodynamic measurements and spectral indices for the last 5 minutes preceding the tilt induced syncope, the study found that the SAP, R-R interval, and HF changed simultaneously during the 30-second period immediately before the tilt induced syncope. Further, the HF was positively correlated with the R-R interval and negatively correlated with the SAP. In conclusion, continuous spectral analysis of the R-R interval demonstrated increased vagal influence on the heart in tilt induced syncope. (PACE 2003; 26[Pt. I]:571–578). [ABSTRACT FROM AUTHOR]

Cells of spleen and lymph nodes were obtained from mice subcutaneously injected with BeCl2 once a week over a 6-week period. These cells were washed twice in cold phosphate-buffered saline and suspended at a final concentration of 2 × 107 cells in 1 ml of buffer. Subsequently, 0.5 ml of the suspension was injected into normal mice intravenously (passive transfer). The findings of the experiments using these mice are summarized as follows: (1) The footpad reaction test was performed 24 hrs after passive transfer. The mice receiving spleen cells or lymph node cells from mice sensitized with BeCl2 developed significant footpad swelling 24 and 48 hrs after challenge of BeCl2 as the antigen. (2) After passive transfer with sensitized spleen cells or lymph node cells the ears of the mice were painted with 7% BeCl2 in ethyl alcohol. Ears of these mice showed significant swelling as compared with those of controls. (3) The migration of peritoneal cells from mice receiving spleen or lymph node cells from sensitized mice was inhibited when tested in medium containing the antigen of BeCl2. From our present experiments, it was suggested that the beryllium sensitizing ability was related to active as well as passive cell-mediated immunity. [ABSTRACT FROM AUTHOR]

The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto) concentrations were increased in pregnancy. Regardless of pregnancy or nonpregnancy, the Proto concentration was decreased after Be injection. Delta-aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D) activities in blood were significantly elevated in the pregnant untreated (Con-pregnant) group, compared to the nonpregnant mice untreated (Connonpregnant) and nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D activity of the pregnant mice treated with Be (Be-pregnant group) tended to decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be-pregnant group was significantly lower compared with that of the Con-pregnant group. The ALA-D and PBG-D activities in the spleen were also significantly elevated in the Con-pregnant group, compared to nonpregnant groups. However, it was noted that these values in the Be-pregnant group were almost the same as that of the Con-nonpregnant group and were significantly lower than that in the Con-pregnant group. The elevation of ALA-D and PBGD activities in the blood and spleen, which play a role in the hematopoietic function of mice, was observed in the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon was not observed in the Be-pregnant mice, it suggesting that Be suppressed the pregnancy-induced increase in hematopoietic function. [ABSTRACT FROM AUTHOR]

Abstract: A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus. [Copyright &y& Elsevier]

Purpose: Besides the high rates of morbidity and mortality, atrial fibrillation (AF) is also associated with impairment of quality-of-life (QOL). However, reports covering non-selected AF population within Asian countries remain scarce. The objective of the Keio interhospital Cardiovascular Studies-atrial fibrillation (KiCS-AF) registry is to clarify the baseline and QOL profiles of the AF patients at the time of initial referral to identify areas for improvement and country-specific gaps., Participants: The KiCS-AF registry is a multicentre, prospective cohort study designed to specifically recruit AF patients newly referred to the 11 network hospitals within the Kanto area of Japan. The registry completed its enrolment in June 2018. All patients were requested to answer the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire both at baseline and 1 year, with planned clinical follow-up for 5 years. The registry also assessed individual treatment strategies including rate and rhythm control, stroke prophylaxis, and their impacts on patient-reported QOL., Findings to Date: As of December 2016, 2464 AF patients were registered; their mean age was 67.1 years (SD, 11.7), majority (69.7%; n=1717) were men and 49.2% presented with paroxysmal AF. The mean CHA 2 DS 2 -VASc (cardiac failure or dysfunction, hypertension, age ≥75 years, diabetes, stroke including vascular disease, age 65-74 years, and sex category [female]) score was 2.3 (SD, 1.6) and oral anticoagulant therapy was used for 88.6% of patients with CHA 2 DS 2 -VASc scores ≥2. The median AFEQT-overall summary score was 79.1 (IQR, 66.6-89.1). Roughly 50% had significantly impaired QOL (ie, AFEQT <80) at baseline. Currently, 2307 eligible patients (93.6%) have completed the 1-year follow-up, of which 2072 patients (89.8%) answered the second AFEQT questionnaire., Future Plans: The KiCS-AF allowed for extensive investigation of AF-related QOL in a non-selected population with long-term follow-up using a rigorously validated QOL assessment tool. Almost half of patients had impaired QOL at baseline. Further investigations aimed at providing care and improving patient-reported QOL are required., Competing Interests: Competing interests: SK received an unrestricted research grant for the Department of Cardiology at Keio University School of Medicine from Bayer Pharmaceutical and Daiichi Sankyo; reported receiving grants from Bayer Yakuhin Ltd and Daiichi Sankyo; and reported receiving personal fees from Bristol-Myers Squibb. TK received grants from Bayer Yakuhin Ltd. JS received personal fees from Novartis, AstraZeneca, Janssen, Bayer, Boehringer Ingelheim, Regeneron, Corvia and United Healthcare; reported receiving grants from Bayer and Abbott Vascular; and reported owning equity in Health Outcomes Sciences. ST received grants and personal fees from Bayer and reported receiving personal fees from Daiichi Sankyo and Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to determine the relationship between the prevalence of in-hospital complications and annual institutional patient volume in a population of patients undergoing percutaneous coronary intervention (PCI)., Methods: Clinical data of patients receiving PCI between January 2010 and June 2015 were collected from 14 academic institutions in the Tokyo area and subsequently used for analysis. We employed multivariate hierarchical logistic regression models to determine the effect of institutional volume on several in-hospital outcomes, including in-hospital mortality and procedure-related complications., Results: A total of 14 437 PCI cases were included and categorised as receiving intervention from either lower-volume (<200 procedures/year, n=6 hospitals) or higher-volume (≥200 procedures/year, n=8 hospitals) institutions. Clinical characteristics differed significantly between the two patient groups. Specifically, patients treated in higher-volume hospitals presented with increased comorbidities and complex coronary lesions. Unadjusted mortality and complication rate in lower-volume and higher-volume hospitals were 1.3% and 1.2% (p=0.0614) and 6.2% and 8.1% (p=0.001), respectively. However, multivariate hierarchical logistic regression models adjusting for differences in the patient characteristics demonstrated that institutional volume was not associated with adverse clinical outcomes., Conclusions: In conclusion, we observed no significant association between annual institutional volume and in-hospital outcomes within the contemporary PCI multicentre registry., Trial Registration Number: UMIN R000005598., Competing Interests: Competing interests: Dr. Kohsaka has received grants from Bayer Yakuhin and Daiichi-Sankyo; has received lecture fees from Bayer Yakuhin and Bristol-Myers Squibb.

In our previous rodent studies, the paclitaxel (PTX)-incorporating polymeric micellar nanoparticle formulation NK105 had showed significantly stronger antitumor effects and reduced peripheral neurotoxicity than PTX dissolved in Cremophor ® EL and ethanol (PTX/CRE). Thus, to elucidate the mechanisms underlying reduced peripheral neurotoxicity due to NK105, we performed pharmacokinetic analyses of NK105 and PTX/CRE in rats. Among neural tissues, the highest PTX concentrations were found in the dorsal root ganglion (DRG). Moreover, exposure of DRG to PTX ( C max&#95;PTX and AUC 0-inf.&#95;PTX ) in the NK105 group was almost half that in the PTX/CRE group, whereas exposure of sciatic and sural nerves was greater in the NK105 group than in the PTX/CRE group. In histopathological analyses, damage to DRG and both peripheral nerves was less in the NK105 group than in the PTX/CRE group. The consistency of these pharmacokinetic and histopathological data suggests that high levels of PTX in the DRG play an important role in the induction of peripheral neurotoxicity, and reduced distribution of PTX to the DRG of NK105-treated rats limits the ensuing peripheral neurotoxicity. In further analyses of PTX distribution to the DRG, Evans blue (Eb) was injected with BODIPY ® -labeled NK105 into rats, and Eb fluorescence was observed only in the DRG. Following injection, most Eb dye bound to albumin particles of ~8 nm and had penetrated the DRG. In contrast, BODIPY ® -NK105 particles of ~90 nm were not found in the DRG, suggesting differential penetration based on particle size. Because PTX also circulates as PTX-albumin particles of ~8 nm following injection of PTX/CRE, reduced peripheral neurotoxicity of NK105 may reflect exclusion from the DRG due to particle size, leading to reduced PTX levels in rat DRG (275)., Competing Interests: Disclosure All authors are employees of Nippon Kayaku Co., Ltd. The authors report no other conflicts of interest in this work.

Background: Preprocedural dual antiplatelet therapy (DAPT) in percutaneous coronary interventions (PCI) has been shown to improve outcomes; however, the efficacy of the procedure and its complications in Japanese patients remain largely unexplored, so we examined the risks and benefits of DAPT before PCI and its association with in-hospital outcomes., Methods and results: We analyzed data from patients who had undergone PCI at 12 centers within the metropolitan Tokyo area between September 2008 and September 2013.Our study group comprised 6,528 patients, of whom 2,079 (31.8%) were not administered preprocedural DAPT. Non-use of preprocedural DAPT was associated with death, postprocedural shock, or heart failure (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.10-1.96, P=0.009), and postprocedural myocardial infarction (OR: 1.41, 95% CI: 1.18-1.69, P<0.001) after adjusting propensity scores for known predictors of in-hospital complications. Non-use of DAPT was not associated with procedure-related bleeding complications (OR: 0.98, 95% CI: 0.71-1.59, P=0.764)., Conclusions: Approximately one-third of the patients who underwent PCI did not receive preprocedural DAPT despite guideline recommendations. Our results indicate that patients undergoing PCI with DAPT have a lower risk of postprocedural cardiac events without any increased bleeding risk. Further studies are needed to implement the use of DAPT in real-world PCI.

Paclitaxel Inj. [NK] (test; paclitaxel, CAS 33069-62-4) is a generic version of the drug from the originator (reference). Both drugs contain the same active ingredient and showed identical pharmacokinetics in patients in the previous study; however, these two drugs may have different safety profiles because they contain different inactive ingredients. Thus, in this study, peripheral neurotoxicity, one of the dose-limiting toxicities of the reference, was compared between the test and the reference in rats electrophysiologically and histopathologically. In a nerve conduction study, the amplitude of the caudal sensory nerve action potential decreased significantly after either the test or the reference administration, compared with the amplitude after saline administration, but no significant differences were observed between the two drugs. Histopathologically, apparent degeneration of the myelinated fibers in the sciatic and the sural nerves was seen after either the test or the reference injection, compared with after saline injection, but no apparent differences were observed between the two formulations. These results suggest that no significant difference in peripheral neurotoxicity exists between the test and the reference in rats.

Background: The slope of the relationship between ventilation and carbon dioxide production (VE/VCO2 slope), obtained during symptom-limited ramp exercise testing, reflects exercise ventilatory efficiency. Importantly, the VE/VCO2 slope is related to prognosis in patients with congestive heart failure (CHF). The aim of the present study was to determine the relationship between the institution of beta-blockers, carvedilol or metoprolol, and the VE/VCO2 slope during exercise in patients with CHF., Methods and Results: Fifty-seven patients with New York Heart Association functional class II or III with a radionuclide left ventricular ejection fraction (LVEF) of less than 40% received carvedilol or metoprolol in a randomized fashion. The VE/VCO2 slope, LVEF and plasma brain natriuretic peptide (BNP) concentration were determined before and after 16 weeks of treatment. LVEF improved (p<0.01), but the VE/VCO2 slope and BNP did not. A significant improvement in the VE/VCO2 slope was observed in patients with LVEF <29% or BNP >63 pg/ml (respective baseline median values) (p<0.05, p<0.05). In patients with BNP >63 pg/ml, the improvement effect on the VE/VCO2 slope with carvedilol was significantly greater than that with metoprolol (p<0.05) and a significant improvement in the VE/VCO2 slope was observed only in those who took carvedilol (p<0.01)., Conclusions: The VE/VCO2 slope was not improved after beta-blocker therapy in any of the patients. However, it did improve in patients with a lower LVEF or higher BNP level at baseline, and carvedilol was more effective than metoprolol in improving the VE/VCO2 slope in patients with higher BNP levels at baseline.