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Keiichiro Yoshioka,1 Mitsuhiro Abe,1 Yuki Shiko,2 Ken Koshikawa,1 Yohei Kawasaki,2 Shunichiro Iwasawa,1 Jiro Terada,1,3 Kenji Tsushima,3 Koichiro Tatsumi,1 Takuji Suzuki1 1Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; 2Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan; 3Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Chiba, JapanCorrespondence: Mitsuhiro Abe, Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-8670, Japan, Tel +81 43 222 2576, Fax +81 43 226 2176, Email mthrsgnm@chiba-u.jpBackground/Aim: Nab-paclitaxel (Nab-PTX) has been widely used to treat several advanced cancers. Nab-PTX can cause drug-induced lung injury (DILI); however, its clinical and radiographic features have not been clarified. We aimed to assess the clinical characteristics of Nab-PTX-induced lung injury and identify its associated risk factors.Patients and Methods: We retrospectively investigated 304 patients who received Nab-PTX at Chiba University Hospital between November 2010 and November 2017. We obtained information regarding the clinical course, laboratory findings, and chest computed tomography findings from their medical records.Results: Forty-one patients (13%) developed DILI. Grade 1 lung injury occurred in 27 patients (8.8%), grade 2, 8 patients (2.6%); grade 3, 3 patients (0.9%); grade 4, 1 (0.3%); and grade 5, 2 (0.6%). Multivariate analysis revealed that age > 56 years (odds ratio [OR]: 3.0), pre-existing interstitial lung changes (OR: 3.2), and combined drugs with gemcitabine (OR: 2.7) were independent risk factors for DILI owing to Nab-PTX administration.Conclusion: Nab-PTX-induced lung injury is not rare; however, most cases are asymptomatic (grade 1). Older age, pre-existing interstitial lung changes, and combined drugs with gemcitabine could increase the incidence of Nab-PTX-induced lung injury; such patients should be treated with greater care.Keywords: drug-induced lung injury, gemcitabine, multivariate analysis, nab-paclitaxel, risk factor

Masashi Sakayori,1 Jiro Terada,1 Mitsuhiro Abe,1 Yasutaka Hirasawa,1 Kenichi Suzuki,1 Keiichiro Yoshioka,1 Kenji Tsushima,2 Koichiro Tatsumi11Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; 2Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Chiba 286-8686, JapanPurpose: Although pirfenidone (PFD) is a key drug for the treatment of idiopathic pulmonary fibrosis (IPF), differences in tolerability between elderly and young patients remain unclear. This study aimed to investigate age-related differences in adverse drug reactions to PFD and to evaluate whether patient age influences the safety and tolerability of PFD in clinical practice.Patients and method: One hundred fifty-four patients with IPF were treated with PFD in our institution between May 2009 and April 2017; these patients were classified into 2 groups on the basis of age: ≥75 years of age (elderly patients) and

Takuma Matsumura,1 Jiro Terada,1 Chikara Yoshimura,2 Ken Koshikawa,1 Taku Kinoshita,1 Misuzu Yahaba,1 Kengo Nagashima,3 Seiichiro Sakao,1 Koichiro Tatsumi1 1Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; 2Department of Respiratory and Sleep Medicine, Fukuoka University School of Medicine, Fukuoka, Japan; 3Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan Purpose: Although patients with suspected obstructive sleep apnea (OSA) might suffer difficulty in falling asleep during overnight polysomnography (PSG), standard hypnotics to obtain sleep during PSG have not been established. The aim of this study was to investigate the safety and efficacy of a new hypnotic agent, suvorexant, a dual orexin receptor antagonist, for insomnia in suspected OSA patients during in-laboratory PSG.Patients and methods: An observational study was conducted during PSG for 149 patients with suspected OSA who had no insomnia at home. Patients with difficulty in falling asleep during PSG were optionally permitted to take single-use suvorexant. Patients with residual severe insomnia (>1 hour) after taking suvorexant were permitted to take an add-on use zolpidem. Clinical data and sleep questionnaire results were analyzed between a no insomnia group (without hypnotics) and an insomnia group (treated with suvorexant).Results: Among 84 patients who experienced insomnia during PSG and required hypnotics (the insomnia group; treated with suvorexant), 44 (52.4%) achieved sufficient subjective sleep with single-use of suvorexant, while the other 40 (47.6%) required suvorexant plus zolpidem. An apnea hypopnea index (AHI) of ≥5 was observed in 144 out of 149 patients with predominantly obstructive respiratory events. Among those patients, 70.8% in the no insomnia group and 63.1% in the insomnia group had severe OSA. Regarding both subjective sleep time and morning mood, significant differences between the no insomnia group and the insomnia group were not observed. No patient taking suvorexant had an adverse event, such as delirium or falling.Conclusion: Single-use suvorexant seems to be a safe and effective (but mild) hypnotic agent for suspected OSA patients with insomnia during in-laboratory PSG. Keywords: insomnia, suvorexant, polysomnography, obstructive sleep apnea, zolpidem, natural sleep

Mitsuhiro Abe,1 Kenji Tsushima,1,2 Masashi Sakayori,1 Kenichi Suzuki,1 Jun Ikari,1 Jiro Terada,1 Koichiro Tatsumi1 1Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba city, Chiba 260-8670, Japan; 2Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Narita city, Chiba 286-8686, Japan Introduction: The INPULSIS-ON trial demonstrated that nintedanib reduced decline in forced vital capacity (FVC) and low pulmonary function (%FVC < 50%) of patients with idiopathic pulmonary fibrosis (IPF). However, there is no sufficient evidence in real world.Objectives: Reveal the utility and adverse events of nintedanib for severe IPF patients.Methods: This was a single-center retrospective study. Patients who met the eligibility criteria of the INPULSIS trial (%FVC ≥ 50%; %DLCO [diffusing capacity of the lung carbon monoxide % predicted] ≥ 30%) were classified as Mild to Moderate Group (n = 34); patients who did not meet the criteria were classified as Severe Group (n=17).Results: The body mass index (24.7 ± 3.4 vs 22.4 ± 3.6 kg/m2; P = 0.021) were significantly low in Severe Group. Main adverse events (diarrhea, nausea, liver disorder, and acute exacerbation) tended to be more in Severe Group than in Mild to Moderate Group; however, the difference was not significant (P = 0.76, 0.14, 0.18, and 0.67, respectively). The continuation rates over 12 months tended to be higher in Mild to Moderate Group than in Severe Group (77% vs 44%; P = 0.027). Log-rank test revealed that the prognosis was significantly better in Mild to Moderate Group than in Severe Group (P = 0.014). In the Severe Group, patients who were able to continue nintedanib for more than 3 months had significantly better prognosis compared to those who could not (P = 0.007).Conclusion: The benefit from nintedanib was reduced in patients in Severe Group when compared to those in Mild to Moderate Group; however, the prognosis is expected to improve with control of side effects and long-term administration. It is more important to control the side effects in Severe Group. Keywords: idiopathic pulmonary fibrosis, nintedanib, triple tyrosine kinase inhibitor, INPULSIS trials, forced vital capacity

Abe M, Tsushima K, Sakayori M, et al. Drug Des Devel Ther. 2018;12:3369–3375.On page 3372, last paragraph of “Results” section should read from “In Severe Group, patients who were able to continue nintedanib for more than 3 months (n = 4) exhibited significantly better prognosis compared to those who could not (n = 13) (P = 0.007) (Figure 6).” to “In Severe Group, patients who were able to continue nintedanib for more than 3 months (n = 13) exhibited significantly better prognosis compared to those who could not (n = 4) (P = 0.007) (Figure 6).”Read the orginal article

Mitsuhiro Abe, Kenji Tsushima, Takuma Matsumura, Tsukasa Ishiwata, Yasunori Ichimura, Jun Ikari, Jiro Terada, Yuji Tada, Seiichirou Sakao, Nobuhiro Tanabe, Koichiro Tatsumi Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan Purpose: Acute exacerbation (AE) is an important outcome of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Recombinant human soluble thrombomodulin (rhTM) is a new drug for the treatment of disseminated intravascular coagulation in Japan. The objective of this study was to evaluate the efficacy of rhTM for AE of IPF/NSIP.Methods: Twenty-two patients with AE-idiopathic interstitial pneumonia (16 patients with IPF and six patients with NSIP) were enrolled in our study. Among them, eleven patients were treated with rhTM (rhTM group), and eleven patients were treated without rhTM (non-rhTM group). Patients admitted to our hospital prior to December 2013 were treated with rhTM, while those admitted after January 2014 were treated without rhTM. The primary endpoint was mortality at 90 days after AE treatment. The secondary endpoint was the safety of rhTM for AE-IPF/AE-NSIP. In addition, we examined prognostic factors of AE-IPF/AE-NSIP.Results: The mortality rate was significantly lower in the rhTM group than in the non-rhTM group (mortality rate at 90 days: 36% vs 90%, P=0.023; median survival time: not reached vs 15.0 days, P=0.019). A univariate analysis revealed the respiratory rate (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.00–1.18, P=0.039) and rhTM administration (HR 0.21, 95% CI 0.06–0.77, P=0.013) as predictors of mortality at 90 days, and a multivariate analysis identified rhTM administration (HR 0.025, 95% CI 0.0006–0.94, P=0.046) as an independent predictor of mortality at 90 days. No serious adverse events were observed.Conclusion: The administration of rhTM is associated with reductions in mortality in patients with AE-IPF/NSIP, without causing adverse events. Keywords: recombinant human soluble thrombomoduline, acute exacerbation, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia

The objective of the present study was to determine the frequency of gas retention in the renal vein following carbon dioxide intraosseous venography in the prone position and, while citing references, to examine its onset mechanisms. All percutaneous vertebroplasties performed at our hospital from January to December 2005 were registered and retrospectively analyzed. Of 43 registered procedures treating 79 vertebrae, 28 procedures treating 54 vertebrae were analyzed. Vertebral intraosseous venography was performed using carbon dioxide as a contrast agent in all percutaneous vertebroplasty procedures. In preoperative and postoperative vertebral CT, gas retention in the renal vein and other areas was assessed. Preoperative CT did not show gas retention (0/28 procedures; 0%). Postoperative CT confirmed gas retention in the renal vein in 10 of the 28 procedures (35.7%). Gas retention was seen in the right renal vein in 8 procedures (28.6%), in the left renal vein in 5 procedures (17.9%), in the left and right renal veins in 3 procedures (10.7%), in vertebrae in 22 procedures (78.6%), in the soft tissue around vertebrae in 14 procedures (50.0%), in the spinal canal in 12 procedures (42.9%), and in the subcutaneous tissue in 5 procedures (17.9%). In conclusion, in our study, carbon dioxide gas injected into the vertebra frequently reached and remained in the renal vein. [ABSTRACT FROM AUTHOR]

The burst-mode 3R receiver using monolithic ICs for 10-Gbit/s-class optical access networks is reported. In a point-to-multipoint access system like a passive optical network (PON), the receiver at the optical line terminal (OLT) must be able to handle burst-mode optical packets with significantly different powers and phases. An OLT receiver with high sensitivity with instantaneous response to burst inputs is desired for widening the accommodation area and for high efficiency in PON uplinks. Currently, the diffusion of high-speed Internet connection services represented by fiber to the home services at 1.25 Gbit/s is remarkable and the standardization of the next-generation system operating at 10 Gbit/s has started in IEEE. We first discuss the issues in the implementation of 10-Gbit/s-class PON systems, focusing on securing the accommodation area and the quality of the service comparable with those of the deployed system. Against that background, we propose target specifications for sensitivity, a dynamic range and response speed of the 10-Gbit/s-class burst-mode receiver so as to secure the power budget and the upstream efficiency comparable with those of the already-installed systems. Our burst-mode 3R receiver was designed to meet the above requirements and developed using monolithic ICs of transimpedance amplifier, limiting amplifier, and clock and data recovery circuit fabricated by using SiGe BiCMOS technologies along with a p-i-n photodiode. High sensitivity of , a wide dynamic range of over 16.5 dB, and quick response time of 75 ns were confirmed for burst inputs with extremely different powers. [ABSTRACT FROM PUBLISHER]