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Soichiro Hozawa,1 Keita Ono,2 Naoyuki Makita,3 Hitomi Uchimura,3 Yoshifumi Arita,3 Takehiro Hirai,2 Naoki Tashiro3 1Hiroshima Allergy and Respiratory Clinic, Hiroshima, Japan; 2AstraZeneca K.K., Tokyo, Japan; 3AstraZeneca K.K., Osaka, JapanCorrespondence: Soichiro Hozawa, Hiroshima Allergy and Respiratory Clinic, 6F, 1-9-28 Hikari-machi, Higashi-ku, Hiroshima, 732-0052, Japan, Tel +81-82-568-1167, Fax +81-82-568-1239, Email hozawa@vesta.ocn.ne.jpPurpose: Japanese guidelines recommend that patients with uncontrolled asthma be referred by non-specialists to specialists (allergists and/or pulmonologists). This study investigated the reality of clinical practice in asthma patients referred to specialists in Japan.Patients and Methods: This was a retrospective, observational cohort study of asthma patients in a health insurance claim database (Cross Fact) referred from facilities with non-specialists to those with specialists from January 2016 to December 2018. The referred asthma patients were defined as patients with ≥ 4 inhaled corticosteroid (ICS)-containing prescriptions during a 1-year baseline period, with an asthma diagnosis, and who had visited a facility with specialists. Asthma exacerbation, maintenance treatment, laboratory tests, and medical procedures before and after referral were analyzed.Results: Data for 2135 patients were extracted, of which 420 with referral codes were analyzed. The proportion of patients with asthma exacerbations was 50.2% (95% confidence interval [CI]: 45.4– 55.1%) before referral and 37.4% (95% CI: 32.7– 42.2%) after, a significant decrease (P< 0.001; McNemar test). The proportions of patients prescribed ICS alone, long-acting beta-agonists (LABA), and ICS/LABA were lower after referral than before, but the proportions of patients prescribed long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, and biologics increased after referral. More asthma-related laboratory tests were performed after referral, and spirometry incidence increased from 16.4% before referral to 51.4% after referral.Conclusion: This study shows a decrease in asthma exacerbations, change in asthma treatments, and increase in laboratory tests after referral to a specialist, suggesting that referrals to specialists lead to better management of asthma.Keywords: asthma, database, referral, specialist, symptom exacerbation

Yuki Abe,1 Masaru Suzuki,1 Hiroshi Shima,2 Yusuke Shiraishi,2 Naoya Tanabe,2 Susumu Sato,2 Kaoruko Shimizu,1 Hirokazu Kimura,1 Hironi Makita,1,3 Toyohiro Hirai,2 Satoshi Konno,1 Masaharu Nishimura1,3 1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8638, Japan; 2Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan; 3Hokkaido Medical Research Institute for Respiratory Diseases, Chuo-ku, Sapporo, 060-0063, JapanCorrespondence: Masaru SuzukiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email suzumasa@med.hokudai.ac.jpPurpose: Low body mass index (BMI) has been reported to be associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). In contrast, a detailed analysis of the association between body weight change over time and prognosis is not sufficient, particularly in Japanese patients with COPD who have been reported to be much thinner compared to Westerners. This study aimed to investigate the relationship between annual body weight change and long-term prognosis in Japanese patients with COPD in two independent cohorts.Patients and Methods: We analyzed 279 patients with COPD who participated in the Hokkaido COPD cohort study as a discovery cohort. We divided participants into three groups according to quartiles of annual body weight change calculated by the data from the first 5 years: weight loss group ( 0.20 kg/year). The association between annual body weight change and prognosis was replicated in the Kyoto University cohort (n = 247).Results: In the Hokkaido COPD cohort study, the weight loss group had significantly worse mortality than the other groups, whereas there was no difference in BMI at baseline. In the multivariate analysis, annual body weight change was an independent risk factor for all-cause mortality, which was confirmed in the Kyoto University cohort.Conclusion: Annual body weight loss is associated with poor prognosis in Japanese patients with COPD, independent of baseline BMI. Longitudinal assessment of body weight is important for the management of COPD.Keywords: annual body weight change, body mass index, chronic obstructive pulmonary disease, mortality, prognosis, weight loss

Hideki Shibata, Takeshi Aoki, Tomotake Koizumi, Tomokazu Kusano, Tatsuya Yamazaki, Kazuhiko Saito, Takahito Hirai, Kodai Tomioka, Yusuke Wada, Tomoki Hakozaki, Yoshihiko Tashiro, Koji Nogaki, Kosuke Yamada, Kazuhiro Matsuda, Akira Fujimori, Yuta Enami, Masahiko Murakami Division of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, Tokyo, JapanCorrespondence: Takeshi AokiDivision of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, JapanTel +81-3-3784-8000Fax +81-3-3784-5835Email takejp@med.showa-u.ac.jpPurpose: Bile duct injury is one of the most serious complications of laparoscopic cholecystectomy. Intraoperative indocyanine green (ICG) cholangiography is a safe and useful navigation modality for confirming the biliary anatomy. ICG cholangiography is expected to be a routine method for helping avoid bile duct injuries.Patients and Methods: We examined 25 patients who underwent intraoperative cholangiography using ICG fluorescence. Two methods of ICG injection are used: intrabiliary injection (percutaneous transhepatic gallbladder drainage [PTGBD], gallbladder [GB] puncture and endoscopic nasobiliary drainage [ENBD]) at a dosage of 0.025 mg during the operation or intravenous injection with 2.5 mg ICG preoperatively.Results: There were 24 patients who underwent laparoscopic cholecystectomy and 1 patient who underwent hepatectomy. For laparoscopic cholecystectomy, the average operation time was 127 (50– 197) minutes, and estimated blood loss was 43.2 (0– 400) g. The ICG administration route was intravenous injections in 12 cases and intrabiliary injection in 12 cases (GB injection: 3 cases, PTGBD: 8 cases, ENBD:1 case). The course of the biliary tree was able to be confirmed in all cases that received direct injection into the biliary tract, whereas bile structures were recognizable in only 10 cases (83.3%) with intravenous injection. The postoperative hospital stay was 4.6 (3– 9) days, and no postoperative complications (Clavien–Dindo ≧IIIa) were observed. For hepatectomy, a tumor located near the left Glissonian pedicle was resected using a fluorescence image guide. Biliary structures were fluorescent without injury after resecting the tumor. No adverse events due to ICG administration were observed, and the procedure was able to be performed safely.Conclusion: ICG fluorescence imaging allows surgeons to visualize the course of the biliary tree in real time during cholecystectomy and hepatectomy. This is considered essential for hepatobiliary surgery to prevent biliary tree injury and ensure safe surgery.Keywords: indocyanine green fluorescent imaging, navigation surgery, near-infrared fluorescent cholangiography

Hiroyuki Yokoyama,1 Takashi Hirai,1 Tetsuya Nagata,2 Mitsuhiro Enomoto,1 Hidetoshi Kaburagi,1 Li Leiyo,1 Takayuki Motoyoshi,1 Toshitaka Yoshii,1 Atsushi Okawa,1 Takanori Yokota2 1Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; 2Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo 113-8519, JapanCorrespondence: Takashi Hirai; Takanori Yokota Email Hirai.orth@tmd.ac.jp; tak-yokota.nuro@tmd.ac.jpPurpose: Pathological stimuli or injury to the peripheral nervous system can trigger neuropathic pain with common clinical features such as allodynia and hypersensitivity. Although various studies have identified molecules or genes related to neuropathic pain, the essential components are still unclear. Therefore, in this study, we investigated the molecular and genetic factors related to neuropathic pain.Methods: We extracted candidate genes in the dorsal root ganglion (DRG) from three nerve injury mouse models and a sham-operated model (sciatic nerve ligation and resection, sural nerve resection, spared nerve injury [SNI], and sham) using DNA microarray to elucidate the genes responsible for the neuropathic pain mechanism in the SNI model, which exhibits hypersensitivity in the hindpaw of the preserved sural nerve area. We eliminated as many biases as possible. We then focused on an upregulated endogenous vasopressin receptor and clarified whether it is closely associated with traumatic neuropathic pain using a knockout mouse and drug-mediated suppression of the gene.Results: Algorithm analysis of DNA microarray results identified 50 genes significantly upregulated in the DRG of the SNI model. Two independent genes—cyclin-dependent kinase-1 (CDK-1) and arginine vasopressin receptor 1A (V1a)—were subsequently identified as candidate SNI-specific genes in the DRG by quantitative PCR analysis. Administration of V1a agonist to wild-type SNI mice significantly alleviated neuropathic pain. However, V1a knockout mice did not exhibit higher hypersensitivity to mechanical stimulation than wild-type mice. In addition, V1a knockout mice showed similar pain behaviors after SNI to wild-type mice.Conclusion: Through the DNA microarray analysis of several neuropathic models, we detected specific genes related to chronic pain. In particular, our results suggest that V1a in the DRG may partially contribute to the mechanism of neuropathic pain.Keywords: neuropathic pain, arginine vasopressin 1a, peripheral nerve injury, dorsal root ganglion, microarray, molecular target

Abe Y, Suzuki M, Shima H, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:3243–3253. The authors have advised there is an error with the ethics approval number of Kyoto University on pages 3245 and 3252. On page 3245, Kyoto University Cohort section, last sentence, the text “(E182 and R03112)” should read “(E182, R0311-2, and R1660-1)”. On page 3252, Ethics Approval and Informed Consent section, the text “(E182 and R0311-2)” should read “(E182, R0311-2, and R1660-1)”. The authors apologize for these errors. Read the original article