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Takeshi Osonoi, Shinichiro Shirabe, Miyoko Saito, Mitsuru Hosoya, Norie Watahiki, Satako Douguchi, Kensuke Ofuchi, Makoto Katoh Naka Kinen Clinic, Naka-shi, Ibaraki, JapanCorrespondence: Makoto Katoh, Naka Kinen Clinic, 745-5 Nakadai, Naka-shi, Ibaraki, 311-0113, Japan, Tel +81 29 353 2800, Fax +81 29 295 5400, Email m-katou@kensei-kai.comPurpose: In this study, we examined the effects of dapagliflozin on changes in hematopoiesis, iron metabolism, and body composition indices in elderly type 2 diabetic patients with renal impairment and investigated the potential of dapagliflozin to treat renal anemia.Patients and Methods: The participants were elderly type 2 diabetics with renal impairment, and the indices of diabetes management, hematopoiesis, iron metabolism, and body composition were compared before and after dapagliflozin treatment.Results: Fourteen subjects were given dapagliflozin 5 mg once daily for 12 weeks, three of whom had eligibility criteria deviations, such as serum ferritin < 50 ng/mL. For this purpose, 14 subjects were analyzed as full analysis set (FAS) and 11 as per-protocol set (PPS). FAS analysis revealed that dapagliflozin had no effect on hemoglobin A1c after 12 weeks but significantly decreased body mass index, significantly increased hemoglobin, hematocrit, and red blood cell count, significantly decreased log ferritin level only of iron metabolism index, and no important change in body water content. PPS analysis, on the other hand, revealed that dapagliflozin 12-week treatment showed a significant decrease in log hepcidin, serum iron, and transferrin saturation.Conclusion: These findings suggest that a 12-week course of dapagliflozin causes an increase in hemoglobin levels due to its hematopoietic effects in elderly type 2 diabetics with renal impairment, but that these effects may be independent of body water loss and iron metabolism improvement.Keywords: dapagliflozin, anemia, hemoglobin, iron metabolism, body composition

Atsuho Morita,1 Ho Namkoong,2 Kazuma Yagi,1 Takanori Asakura,1 Makoto Hosoya,3 Hiromu Tanaka,1 Ho Lee,1 Takunori Ogawa,1 Tatsuya Kusumoto,1 Shuhei Azekawa,1 Kensuke Nakagawara,1 Hirofumi Kamata,1 Makoto Ishii,1 Koichi Fukunaga,1 Hiroyuki Ozawa,3 Naoki Hasegawa2 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan; 3Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, JapanCorrespondence: Ho Namkoong, Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan, Tel +81 03 3353 1211, Fax +81 03 5843 6167, Email hounamugun@gmail.comPurpose: Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for effect while minimising systemic adverse effects, was recently approved for treating Mycobacterium avium complex (MAC) infections. The international Phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few studies have examined the efficacy and adverse effects of ALIS using real-world data. We identified the clinical outcome and adverse effects of ALIS in the early phase of treatment, for more effective and safe use in clinical practice.Patients and Methods: The study population consisted of patients with MAC lung disease (MAC-LD), introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms, adverse effects, and the serum amikacin concentrations of the early phase of ALIS inhalation therapy were examined.Results: A total of 11 patients (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients exhibited a positive culture at the beginning of ALIS inhalation. Three of the six patients (50.0%) who were initially sputum-smear-positive were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 μg/mL for the first and third inhalations, respectively. Trough serum concentrations just before the third inhalation were < 1.2 μg/mL in all patients.Conclusion: ALIS therapy might be a treatment option for patients with refractory MAC infection with long disease duration and a poor response to guideline-based therapy.Keywords: Mycobacterium avium complex, MAC, nontuberculous mycobacteria, NTM, amikacin liposome inhalation suspension, ALIS

Aims: To examine the relation between enteroviral infection, especially group A coxsackieviral infection, and acute febrile illness over two summers using tissue culture and polymerase chain reaction (PCR). Methods: Throat [...]

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the relationships between serum cytokine concentrations and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in premature infants. METHODS: Serum was collected at 0 and 7 days after birth from 36 premature infants born at <32 weeks of gestation. We examined the relationships between 30 cytokine concentrations and CAM, BPD, and other perinatal factors. RESULTS: On day 0, GM-CSF, IL-15, IL-17, IL-2, IL-2R, VEGF, and MIG concentrations were significantly higher in the CAM group (n = 17) than in the non-CAM group (n = 19). These concentrations had decreased by day 7 and were similar in both groups. The IL-12p70 concentration on day 0 was significantly lower in the BPD group (n = 16) than in the non-BPD group (n = 15). BPD incidence was similar between the CAM and non-CAM groups. CONCLUSIONS: These data support the hypothesis that intrauterine inflammation is not a primary risk factor for BPD. The immunological environment at birth or soon after, rather than intrauterine fetal inflammation (e.g., CAM), is a primary risk factor for BPD onset in preterm infants. Decreased inflammatory responses are particularly relevant, as indicated by the relationship between BPD and low serum IL-12p70 concentrations on day 0. [ABSTRACT FROM AUTHOR]