Search

Tomoko Tajiri,1 Motohiko Suzuki,2,3 Takeo Kutsuna,4 Hirono Nishiyama,1 Keima Ito,1 Norihisa Takeda,1 Kensuke Fukumitsu,1 Yoshihiro Kanemitsu,1 Satoshi Fukuda,1 Takehiro Umemura,1 Hirotsugu Ohkubo,1 Ken Maeno,1 Yutaka Ito,1 Tetsuya Oguri,1 Masaya Takemura,1 Kosho Yoshikawa,4 Akio Niimi1 1Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 2Department of Otorhinolaryngology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 3Department of Otorhinolaryngology, Nagoya City East Medical Center, Nagoya, Aichi, Japan; 4Department of Respiratory Medicine, Daido Hospital, Nagoya, Aichi, JapanCorrespondence: Tomoko Tajiri, Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan, Tel +81-52-853-8216, Email tomokot@med.nagoya-cu.ac.jpObjective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the “one airway, one disease” concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens.Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab.Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p< 0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab.Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.Keywords: omalizumab, antigen-specific IgE, pollen, allergic rhinitis, allergic asthma

Keima Ito,1 Tomoko Tajiri,1 Hirono Nishiyama,1 Ryota Kurokawa,1 Jenifer Maries Go Yap,1 Norihisa Takeda,1 Kensuke Fukumitsu,1 Yoshihiro Kanemitsu,1 Satoshi Fukuda,1 Takehiro Uemura,1 Hirotsugu Ohkubo,1 Ken Maeno,1 Yutaka Ito,1 Tetsuya Oguri,1,2 Masaya Takemura,1,2 Akio Niimi1 1Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanCorrespondence: Tomoko Tajiri, Email tomokot@med.nagoya-cu.ac.jpPurpose: Recently, single-inhaler triple therapy (SITT) has demonstrated efficacy in patients with uncontrolled asthma who were symptomatic despite treatment with inhaled corticosteroids/long-acting β 2 agonists. However, the characteristics of patients who benefit from SITT remain unclear in the real-world. The aim of this study was to examine the predictors of responsiveness to SITT in patients with asthma.Patients and Methods: A total of 45 patients with asthma who had regularly visited our respiratory clinic and were started on SITT from March 2019 to March 2021 were retrospectively analyzed. Patients’ demographic characteristics, residual respiratory symptoms, type 2 biomarkers, and lung function before SITT were assessed from the patients’ medical records. Predictors of responsiveness to four-week SITT were evaluated in these patients. The definition of responders was based on the physician-assessed global evaluation of treatment effectiveness.Results: Thirty-four (75%) of 45 patients were identified as responders to SITT. Non-responders showed significantly lower forced vital capacity (FVC) (%predicted) values, and complained of dyspnea more frequently than responders before SITT (p = 0.01 and p = 0.02, respectively). There were no significant differences in demographic characteristics and type 2 biomarkers between responders and non-responders. Clinical predictors of poor response to SITT were residual dyspnea (OR = 0.14, p = 0.02), low FVC (%predicted) values (OR = 1.05, p = 0.01), and FVC (%predicted) < 80% (OR = 0.11, p = 0.02). Multivariate analysis showed that poor response to SITT was associated with residual dyspnea before SITT (OR = 0.14, p = 0.02). On the other hand, patients with residual dyspnea had significantly lower FEF25– 75 (%predicted) values than patients without residual dyspnea before SITT (p = 0.04).Conclusion: Residual dyspnea, reflecting small airways dysfunction, may predict poor responsiveness to short-term SITT in patients with asthma.Keywords: single-inhaler triple therapy, long-acting muscarinic antagonists, asthma, small airways dysfunction, dyspnea

Yasushi Kono,1 Shota Fukuda,1 Akihisa Hanatani,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Haruyuki Taguchi,1 Kenei Shimada2 1Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Osaka, Japan Background: Remote ischemic conditioning (RIC) is a treatment modality that suppresses inflammation and improves endothelial function, which are factors involved in the pathogenesis of heart failure (HF) with reduced left ventricular ejection fraction. Coronary flow reserve (CFR) is a physiological index of coronary microcirculation and is noninvasively measured by transthoracic Doppler echocardiography (TTDE). This study aimed to investigate the effects of RIC on CFR in healthy subjects and patients with HF, through the assessment by TTDE. Methods: Ten patients with HF with left ventricular ejection fraction of less than 40%, and ten healthy volunteers were enrolled in this study. RIC treatment was performed twice a day for 1 week. Our custom-made RIC device was programmed to automatically conduct 4 cycles of 5 minutes inflation and 5 minutes deflation of a blood pressure cuff to create intermittent arm ischemia. CFR measurements and laboratory tests were examined before, and after 1 week of RIC treatment. Results: One week of RIC treatment was well tolerated in both groups. RIC treatment increased CFR from 4.0±0.9 to 4.6±1.3 (mean ± standard deviation) in healthy subjects (P=0.02), and from 1.9±0.4 to 2.3±0.7 in patients with HF (P=0.03), respectively. Systolic blood pressure in healthy subjects, and heart rate in HF patients decreased after RIC treatment (both P

Yasushi Kono,1 Shota Fukuda,1 Kenei Shimada,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Tomoichiro Kubo,1 Satoshi Jissho,1 Haruyuki Taguchi,1 Junichi Yoshikawa,3 Minoru Yoshiyama21Department of Medicine, Osaka Ekisaikai Hospital, Nishi-ku, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Abeno-ku, Osaka, Japan; 3Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanBackground: It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function.Purpose: This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin.Methods: This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration.Results: The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group.Conclusion: The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.Keywords: coronary artery disease, statin, microvascular function

Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = –0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = –0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin–angiotensin blocker treatment regimen.Keywords: diastolic dysfunction, diabetes, urinary albumin to creatinine ratio, losartan, HCTZ

Reaction cross sections (σR) for the neutron-rich nucleus 14B on Be, C, and Al targets have been measured at several energies in the intermediate energy range of 45–120 MeV/nucleon. The present experimental σR show a significant enhancement relative to the systematics of stable nuclei. The nucleon density distribution was deduced through the fitting procedure with the modified Glauber calculation. The necessity of a long tail in the density distribution was found, which is consistent with the valence neutron in 2s1/2 orbital with the small empirical one-neutron separation energy in 14B.

An isomeric state in the proton drip-line nucleus 26P has been observed by the γ-ray spectroscopy. The γ-ray energy and the half-life are 164.4 ± 0.1 keV and 120 ± 9 ns, respectively. For the isomeric transition of the mirror nucleus 26Na, the γ-ray energy of 82.40 ± 0.04 keV and the half-life of 4.35 ± 0.16 μs are also revised. Comparing the experimental reduced transition probabilities of 26Na and 26P with theoretical ones calculated by the shell model with the USDA interaction, the spin-parity (Jπ) of the isomeric state in 26P is most likely to be 1+.

Background: Persistent fever after intravenous immunoglobulin (IVIG) is considered to be a major criterion of IVIG resistance in Kawasaki disease (KD), and a risk factor for the development of coronary artery abnormalities (CAA). However, the importance of