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High-flow nasal cannulas (HFNCs) have become common devices for patients with respiratory failure who are treated in general wards. Few reports have been published on in-hospital mortality associated with the ratio of oxygen saturation (ROX) index, measured by pulse oximetry/fraction of inspired oxygen to respiratory rate, in patients treated with HFNCs. We aimed to examine in-hospital mortality and associated factors in patients who initiated HFNC use in a general ward. Sixty patients who initiated HFNC use in general wards at Kobe University Hospital between December 2016 and October 2020 were retrospectively enrolled. We assessed in-hospital mortality, comorbidities, and ROX index. The in-hospital mortality was 48.3%, and ROX index values were significantly lower in patients who died than in those who did not (at HFNC oxygen therapy initiation; 6.93 [2.73–18.5] vs. 9.01 [4.62–18.1], p = 0.00861). Although the difference was not statistically significant, the change in ROX index values between HFNC initiation and 12 hours after initiation tended to be greater in the patients who died in the hospital (0.732 [−2.84–3.5] vs. −0.35[−4.3–2.6], p = 0.0536). Lower ROX index values may be associated with the in-hospital death of patients who are treated with HFNCs in general wards.

Additional file 3. Uncut blotting images for Budesonide/Glycopyrronium /Formoterol Fumarate Triple Therapy Prevents Pulmonary Hypertension in a COPD Mouse Model via NFκB Inactivation.

Additional file 1: Table S1. List of primers used for qPCR analysis.

Additional file 1. Questionnaire.

Additional file 2: Figure S1. Lymphocyte counts in the BAL fluid of mice from all experimental groups 1 day post-elastase treatment. Figure S2. Immunostaining VEGF-A (A), eNOS (B), and Ki 67 (C) in the lung vasculature of mouse lung of all experimental groups at Pulmonary Hypertension phase. Scale bar:50 uM. Black arrows indicate vessel.

Hypertrophic pulmonary osteoarthropathy (HPO) is a paraneoplastic syndrome characterized by digital clubbing, arthritis, and periostitis. Tumor removal usually leads to the resolution of these symptoms. We herein report the efficacy of crizotinib treatment for treating the symptoms of HPO associated with c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer. A 71-year-old woman presented with a pulmonary tumor and arthritis. She was diagnosed with a ROS1-rearranged lung adenocarcinoma [stage IIIB (cT4N2M0) ] with HPO. Crizotinib dramatically reduced the tumor size and resolved the symptoms. After two months of crizotinib treatment, she underwent lobectomy, and a pathological evaluation revealed ypstage IIIA (ypT3a, ypN1). Crizotinib treatment was effective for reducing the tumor size and improving the symptoms of HPO.

In the human intestinal tract, there are more than 100 trillion symbiotic bacteria, which form the gut microbiota. Approximately 70% of the human immune system is in the intestinal tract, which prevents infection by pathogenic bacteria. When the intestinal microbiota is disturbed, causing dysbiosis, it can lead to obesity, diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, autism spectrum disorder and cancer. Recent metabolomics analyses have also made the association between the microbiota and carcinogenesis clear. Here, we review the current evidence on the association between the microbiota and gastric, bladder, hepatobiliary, pancreatic, lung and colorectal cancer. Moreover, several animal studies have revealed that probiotics seem to be effective for the prevention of carcinogenesis to some extent. In this review, we focused on this relationship between the microbiota and cancer, and considered how to prevent cancer using strategies involving the gut microbiota.

Naoko Katsurada,1 Motoko Tachihara,1 Yukihisa Hatakeyama,1 Kiyoko Koyama,1 Masako Yumura,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Daisuke Hazama,1 Shuntaro Tokunaga,1 Daisuke Tamura,1 Kyosuke Nakata,1 Masatsugu Yamamoto,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Yugo Tanaka,2 Yoshimasa Maniwa,2 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 2Division of General Theocratic Surgery, Kobe University Graduate School of Medicine, Kobe, JapanCorrespondence: Motoko TachiharaDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-5660Fax +81-78-382-5661Email mt0318@med.kobe-u.ac.jpPurpose: Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors > 4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC.Patients and Methods: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0– 1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit.Results: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥ 75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4– 83.7). Two-year RFS was 56.8% (95% CI, 29.7– 76.9).Conclusion: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.Keywords: nab-paclitaxel, carboplatin, adjuvant chemotherapy, non-small cell cancer

Tatsunori Kiriu, Masatsugu Yamamoto, Tatsuya Nagano, Daisuke Hazama, Reina Sekiya, Masahiro Katsurada, Naoko Katsurada, Motoko Tachihara, Kazuyuki Kobayashi, Yoshihiro Nishimura Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, JapanCorrespondence: Masatsugu YamamotoDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-5660Fax +81-78-382-5661Email myamamot@med.kobe-u.ac.jpPurpose: Pseudo-progression (PsPD) is a rare phenomenon observed in

Yuichiro Yasuda,1 Tatsuya Nagano,1 Motoko Tachihara,1 Norio Chihara,2 Kanoko Umezawa,1 Naoko Katsurada,1 Masatsugu Yamamoto,1 Kenji Sekiguchi,2 Kazuyuki Kobayashi,1 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan; 2Division of Neurology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, JapanCorrespondence: Tatsuya NaganoDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Kobe, Hyogo 650-0017, JapanTel +81-783-82-5660Fax +81-783-82-5661Email tnagano@med.kobe-u.ac.jpAbstract: We herein report the case of a 39-year-old Japanese female with eosinophilic pneumonia associated with natalizumab. The patient with bronchial asthma had multiple sclerosis and was treated using natalizumab. The patient was referred to our department because of a persistent cough. A chest computed tomography (CT) scan revealed bilateral patchy consolidation surrounded by ground-glass opacity. A bronchoalveolar lavage (BAL) was performed. Eosinophil levels in the BAL fluid were increased and the patient was consequently diagnosed as eosinophilic pneumonia associated with natalizumab. Therefore, natalizumab treatment was discontinued. Subsequent chest CT findings showed a remarkable improvement without any treatment.Keywords: eosinophilic pneumonia, natalizumab, multiple sclerosis

Mariko Kojima,1 Tatsuya Nagano,1 Kyosuke Nakata,1 Shigeo Hara,2 Naoko Katsurada,1 Masatsugu Yamamoto,1 Motoko Tachihara,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Takeshi Usui,3 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; 2Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; 3Department of Medical Genetics, Shizuoka General Hospital, Shizuoka City, Shizuoka, Japan Abstract: Hypoparathyroidism with sensorineural deafness and renal dysplasia (HDR) syndrome is an autosomal dominant condition caused by mutations of the gene encoding the dual zinc-finger transcription factor, GATA3. A previous study identified some patients with GATA3 gene variants and breast cancer, suggesting that GATA3 variants may contribute to tumorigenesis in estrogen receptor 1-positive breast tumors; however, these patients did not have HDR syndrome. A 32-year-old nonsmoking Japanese woman was histologically diagnosed with lung squamous cell carcinoma associated with HDR syndrome and a c.C952T>C (p.C318R) germline mutation in GATA3. This is the first report describing cancer in a patient with HDR syndrome. Our data indicates that GATA3 mutations may be a potential therapeutic target for lung cancer. Keywords: lung cancer, GATA3, missense variant, hypoparathyroidism, sensorineural deafness, renal dysplasia