Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis: Effects of Treatment With Insulin and Intravenous Fluids and Effects of Bumetanide

ObjectiveCerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking.Research design and methodsWe evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 x 2 factorial study design.ResultsCerebral intracellular pH was decreased during DKA compared with control (mean +/- SE difference -0.13 +/- 0.03; P < 0.001), and lactate/Cr was elevated (0.09 +/- 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (-0.32 +/- 0.10, P = 0.003, and -0.14 +/- 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment.ConclusionsThese data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment--consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease

Satoshi Igawa,1 Noriko Nishinarita,1 Akira Takakura,1 Takahiro Ozawa,1 Shinya Harada,1 Seiichiro Kusuhara,1 Hideyuki Niwa,2 Shinji Hosotani,1 Hideyuki Sone,1 Yoshiro Nakahara,1,3 Tomoya Fukui,1 Hisashi Mitsufuji,4 Masanori Yokoba,5 Masaru Kubota,1 Masato Katagiri,5 Jiichiro Sasaki,6 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan; 2Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Aichi, Japan; 3Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Kanagawa, Japan; 4Kitasato University School of Nursing, Sagamihara 252-0329, Kanagawa, Japan; 5School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan; 6Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan Background: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. Patients and methods: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. Results: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59–83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. Conclusion: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD. Keywords: interstitial lung disease, non-small-cell lung cancer, carboplatin, nab-paclitaxe