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Kae Sunagawa,1,2 Keiji Hirai,3 Sumito Sunagawa,1,2 Norifumi Kamiya,1 Isao Komesu,1 Yusako Sunagawa,1 Hiroshi Sunagawa,1 Ken Nakachi,4 Aizan Hirai,5 Susumu Ookawara,3 Yoshiyuki Morishita3 1Sunagawa Medical Clinic, Okinawa, Japan; 2Division of Endocrinology, Diabetes and Metabolism, Hematology, and Rheumatology, University of the Ryukyus, Okinawa, Japan; 3Division of Nephrology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 4Department of Internal Medicine, Shonan Hospital, Okinawa, Japan; 5Department of Internal Medicine, Chiba Cerebral and Cardiovascular Center, Chiba, JapanCorrespondence: Keiji Hirai, Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Saitama-shi, Saitama-ken, 330-8503, Japan, Tel +81 48 647 2111, Fax +81 48 647 6831, Email keijihirai@kfy.biglobe.ne.jpPurpose: The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease.Patients and Methods: Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months.Results: Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p< 0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p< 0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio.Conclusion: Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.Keywords: empagliflozin, sodium-glucose co-transporter 2 inhibitor, liraglutide, glucagon-like peptide-1 receptor agonist, diabetic kidney disease, diabetic nephropathy

Naoko Kamiya,1 Yukiko Ishikawa,1 Kazuhiko Kotani,2 Shuji Hatakeyama,1,3 Masami Matsumura1 1Division of General Internal Medicine, Jichi Medical University Hospital, Shimotsuke-shi, Tochigi, Japan; 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi, Japan; 3Division of Infectious Diseases, Jichi Medical University Hospital, Shimotsuke-shi, Tochigi, JapanCorrespondence: Naoko Kamiya, Division of General Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan, Tel +81-285-58-7498, Fax +81-285-40-5160, Email m01015no@jichi.ac.jpBackground: Lymphomas, including Hodgkin lymphoma and non-Hodgkin lymphoma, are one of the differentials for peripheral lymphadenopathy and are difficult to diagnose clinically. Biopsy is essential for diagnosing lymphoma, although it is invasive. Non-invasive methods are required to identify patients with suspected lymphoma who should undergo a biopsy. The relevance of the monocyte-to-lymphocyte ratio has recently been reported to be a useful diagnostic marker in children with lymphoma and a prognostic marker of various other diseases. This study aimed to determine the relevance of the monocyte-to-lymphocyte ratio in the diagnosis of lymphoma in adults.Methods: The study included 246 adult outpatients (median age of 49.0 years) presenting with peripheral lymphadenopathy. The final diagnosis was determined by reviewing the medical records. We categorized all patients into either the lymphoma group or the non-lymphoma group. The lymphoma group included patients who underwent biopsy and were diagnosed with lymphoma by histopathology, while the non-lymphoma group included those diagnosed with disease excluding lymphoma. The monocyte-to-lymphocyte ratios were compared between the two groups.Results: Of the participants, 33 (13.4%) were assigned to the lymphoma group. The median age of the lymphoma and non-lymphoma groups were 67.0 years (interquartile range [IQR] 55.5– 75.5 years) and 46.0 years (IQR 36.0– 61.0 years), respectively. The lymphocyte and monocyte levels showed no significant differences between the two groups individually. Nonetheless, the monocyte-to-lymphocyte ratio was significantly higher in the lymphoma group (median, 0.36; IQR, 0.24– 0.73) than in the non-lymphoma group (median, 0.29; IQR, 0.21– 0.43; P = 0.022), independent of lymph node diameter ≥ 1 cm and C-reactive protein levels.Conclusion: This study suggests that the monocyte-to-lymphocyte ratio can be a helpful diagnostic marker for lymphoma in adults with peripheral lymphadenopathy when the etiology is unclear even after a medical interview and physical examination.Keywords: lymphadenopathy, lymphoma, monocyte-to-lymphocyte ratio, diagnostic marker