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Tadashi Kamio,1 Hiroshi Koyama,1 Kiyomitsu Fukaguchi,1 Shuku Sato,2 Wataru Kamata,2 Satomi Okada,2 Yotaro Tamai2 1Division of Critical Care, Shonan Kamakura General Hospital, Kamakura, Kanagawa 247-8533, Japan; 2Department of Hematology, Shonan Kamakura General Hospital, Kamakura, Kanagawa 247-8533, JapanCorrespondence: Tadashi KamioDivision of Critical Care, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, JapanTel +81-467-46-1717Fax +81-467-47-8243Email tadashi-kamio@mail.goo.ne.jpPurpose: Acute promyelocytic leukemia (APL) constitutes 5– 10% of all cases of newly diagnosed acute myeloid leukemia. However, data on the epidemiology and risk factors for acute kidney injury (AKI) in patients with newly diagnosed APL are lacking. This study determined the incidence rate of AKI during induction chemotherapy for patients with newly diagnosed APL and the risk factors for AKI.Patients and Methods: We conducted a retrospective observational study of patients with newly diagnosed APL in the Shonan Kamakura General Hospital between April 2004 and April 2020. Data of 27 patients with newly diagnosed APL were analyzed. The patients were classified as no AKI and AKI stages 1, 2 or 3.Results: The incidence rate of AKI during induction chemotherapy was 40% (11/27). Among patients who developed AKI, four patients experienced AKI stage 3, and two patients required renal replacement therapy. No significant differences were found in the white blood cell count and baseline renal function between the groups; however, D-dimer and C-reactive protein levels upon admission were significantly higher in patients with AKI than in patients without AKI. Among patients who developed AKI, in hospital mortality at 90 days was 36% (4/11), which was significantly higher than among patients without AKI (p = 0.02). Patients who developed AKI were administered vancomycin more frequently, while almost all blood culture results were negative.Conclusion: Incidence of AKI development in patients with newly diagnosed APL during induction chemotherapy was approximately 40%. Moreover, patients who developed AKI tended to be administered vancomycin more frequently. Unnecessary use of vancomycin should be avoided in patients with newly diagnosed APL, and using alternative non-nephrotoxic drugs should be considered for patients at risk of AKI.Keywords: acute promyelocytic leukemia, acute kidney injury, incidence rate, induction chemotherapy

Ayaka Niina,1 Ryoko Kibe,2 Ryohei Suzuki,1 Yunosuke Yuchi,1 Takahiro Teshima,1 Hirotaka Matsumoto,1 Yasushi Kataoka,2 Hidekazu Koyama1 1Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan; 2Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, JapanCorrespondence: Ayaka NiinaLaboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-Cho, Musashino-Shi, Tokyo 180-8602, JapanTel +81 422 31 4151Fax +81 422 31 4560Email a.niina2173@gmail.comPurpose: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT.Patients and methods: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity.Results: Fecal microbiome diversity after FMT resembled that of the healthy donor dog’s fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment.Conclusion: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.Keywords: fecal microbiota transplantation, inflammatory bowel disease, canine, dysbiosis, microbiome, diversity

Katsuhiko Nakatsukasa,1 Hiroshi Koyama,2 Yoshimi Ouchi,1 Kouichi Sakaguchi,1 Yoshifumi Fujita,1 Takayuki Matsuda,3 Makoto Kato,4 Eiichi Konishi,5 Tetsuya Taguchi1 1Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Breast Surgery, Nara City Hospital, Nara, Japan; 3Department of Breast Surgery, Saiseikai Kyoto Hospital, Kyoto, Japan; 4Department of Breast Surgery, Kato Breast Surgery Clinic, Kyoto, Japan; 5Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan Background: The aim of the study was to conduct subgroup analyses of therapeutic effects of 12-month denosumab therapy on the percentage change in bone mineral density (BMD) from baseline in the lumber spine and femoral neck. Materials and methods: We prospectively evaluated the BMD of the lumbar spine and femoral neck of 100 hormone receptor-positive, clinical stage I–IIIA postoperative postmenopausal breast cancer patients, for whom treatment with aromatase inhibitors (AIs) as adjuvant endocrine therapy was scheduled. The primary endpoint was the percent change in lumbar spine BMD from baseline to 12 months. Patient subgroups were analyzed according to baseline variables that are known risk factors for bone loss, including previous AI therapy, age, time since menopause, baseline body mass index (BMI), and baseline BMD T-score. Results: At 12 months, lumbar spine BMD increased by 4.7%; the patients who were administered AI therapy prior to denosumab (n=70) demonstrated a 4.7% increase in BMD, and the patients who received denosumab at the start of AI therapy (n=30) demonstrated a 4.5% increase in BMD (p=0.8385). Additionally, 2.4% and 1.4% increases in BMD of the right and left femoral neck, respectively, were observed. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (5 years), BMI (-1.0) of the right femoral neck were as follows: (2.2%, 2.5%, p=0.7773), (2.6%, 0.9%, p=0.1726), (2.5%, 2.3%, p=0.7594), (2.1%, 2.4%, p=0.2034), (2.1%, 2.9%, p=0.2034), and (2.3%, 2.7%, p=0.6823), respectively. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (5 years), BMI (-1.0) of the left femoral neck were as follows: (1.0%, 1.5%, p=0.1972), (1.2%, 2.7%, p=0.2931), (1.4%, 1.3%, p=0.8817), (-0.1%, 1.6%, p=0.1766), (1.3%, 1.9%, p=0.6465), and (1.5%, 1.1%, p=0.6573), respectively. Conclusion: Twice-yearly treatment with denosumab was associated with increased BMD among Japanese women receiving adjuvant AI therapy, regardless of the baseline characteristics or skeletal site. Keywords: aromatase inhibitor, denosumab

Akinori Kanzaki,1,2 Kiyoshi Matsui,3 Tadahiko Sukenaga,1,2 Koushi Mase,1 Aya Nishioka,1 Tomoharu Tamori,4 Seiko Kataoka,1 Hiroyuki Konya,1 Shin Mizutani,4 Akira Takeda,1 Masato Koseki,1 Tetsuo Nishiura,1 Hidenori Koyama,2 Hajime Sano3 1Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan; 2Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 3Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 4Department of Surgery, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan Abstract: Polymyalgia rheumatica (PMR) is a disease commonly seen in elderly individuals, however, the etiology has not been reported. Typical clinical features include bilateral shoulder pain and morning stiffness, while serologic autoantibody test findings are negative. Approximately 40%–50% of affected patients present with low-grade fever, fatigue, and appetite loss, which we often experience in the field of general medicine, and thus, the condition should not be given low priority. However, knowledge regarding such constitutional manifestations is also limited. We encountered an elderly woman with a fever of unknown origin that developed following a parathyroidectomy for a single parathyroid adenoma, after which severe shoulder pain and morning stiffness emerged, leading to a diagnosis of PMR. The fever developed several days prior to appearance of severe pain, which is an uncommon presentation in PMR cases. Our patient had low-grade inflammation without pyrexia prior to the surgery, which might have been an important reason for the accelerated immoderate immune activation leading to PMR induced by surgery in this case. Furthermore, she was infected with the influenza A virus 3 weeks before coming to us. Some reports have suggested a relationship between the influenza virus or vaccine and PMR. It is difficult to conclude regarding the definite trigger in our patient, though the details of this case should be helpful for a better understanding of the disease. Keywords: polymyalgia rheumatica, fever of unknown origin, immoderate immune activation, parathyroidectomy, influenza A viral infection, single parathyroid adenoma

Makoto Ishitobi,1 Kazuyo Shibuya,2 Yoshifumi Komoike,1 Hiroki Koyama,1 Hideo Inaji1 1Department of Breast and Endocrine Surgery, 2Department of Nursing, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Purpose: The purpose of this study was to evaluate preferences for oral versus intravenous adjuvant chemotherapy among early breast cancer patients (UMIN-CTR number UMIN000004696). Patients and methods: Eighty-two postmenopausal women with estrogen receptor-positive, human epidermal growth-factor receptor 2-negative breast cancer who had completed adjuvant chemotherapy were asked about their preferred route of administration of chemotherapy and the reason. Women also answered questions about their physical and psychological status and quality of life during chemotherapy. Results: Patients who had received oral chemotherapy preferred it more frequently than those who had received intravenous chemotherapy (100% versus 37%, respectively, chi-square =15.5; P

Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II), Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual compression, the patient required blood transfusion for the massive blood loss. She eventually succumbed to respiratory failure. This case report demonstrates that primary breast cancer lesions with skin involvement have the potential to cause massive hemorrhage after bevacizumab-based treatment.Keywords: bevacizumab, breast cancer, necrosis, hemorrhage, adverse event, paclitaxel

Mitsuru Hanada, Hiroshi Koyama, Masaaki Takahashi, Yukihiro MatsuyamaDepartment of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanBackground: Osgood–Schlatter disease (OSD) is one of the common causes of knee pain in active adolescents who play sports. The common age for boys to have OSD is between 12 and 15 years and for girls, between 8 and 12 years. Radiographic studies are helpful in diagnosis and treatment of OSD.Purpose: We examine the age at onset of OSD in detail and investigate the relationship between clinical findings, radiographic bone morphology, and the severity of OSD in adolescents.Results: The average age at onset of knee pain was 12 years and 6 months – 12 years and 9 months in boys, and 12 years and 1 month in girls. Boys were significantly older than girls at onset. In addition, there were significant relationships between duration from first onset to visit to the clinic, radiographic bone stage, body morphology, and radiographic severity. The patients who delayed their visit to the clinic from the first onset of pain and who were older showed a later bone stage and more radiographic severity grade of OSD. There was significant differences concerning weight and body mass index between severity grade I and III. Conclusion: For the age at the onset of OSD, the mean age of boys was significantly older than that of girls. The patients at a later bony stage had a higher severity grade. The boys and girls with OSD who had less weight or body mass index showed less severity.Keywords: Osgood–Schlatter disease, radiographic classification, tibial tuberosity, body morphology

Feline infectious peritonitis viruses (FIPVs) are classified into type I and type II serogroups. Here, we report that feline aminopeptidase N (APN), a cell-surface metalloprotease on the intestinal, lung and kidney epithelial cells, is a receptor for type II FIPV but not for type I FIPV. A monoclonal antibody (MAb) R-G-4, which blocks infection of Felis catus whole fetus (fcwf-4) cells by type II FIPV, was obtained by immunizing mice with fcwf-4 cells which are highly susceptible to FIPV. This MAb also blocked infection of fcwf-4 cells by type II feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV). On the other hand, it did not block infection by type I FIPVs. MAb R-G-4 recognized a polypeptide of relative molecular mass 120-130 kDa in feline intestinal brush-border membrane (BBM) proteins. The polypeptide possessed aminopeptidase activity, and the first 15 N-terminal amino acid sequence was identical to that of the feline APN. Feline intestinal BBM proteins and the polypeptide reacted with MAb R-G-4 (feline APN) inhibited the infectivity of type II FIPV, type II FECV, CCV and TGEV to fcwf-4 cells, but did not inhibit the infectivity of type I FIPVs.