Kentaro Tojo

Reevaluation of the effectiveness of ramosetron for preventing postoperative nausea and vomiting: a systematic review and meta-analysis.

BACKGROUND: Ramosetron has been shown to have a very strong effect for preventing postoperative nausea and vomiting (PONV) in previous meta-analyses. However, these previous meta-analyses included a number of studies by Fujii et al. which have now been proven to have been fabricated. In the present meta-analysis, we reevaluated the effectiveness of ramosetron in preventing PONV after excluding Fujii et al.’s randomized controlled trials. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. All double-blind randomized controlled trials that tested the efficacy of ramosetron compared with a placebo or other drugs as a control in the prophylaxis of PONV were considered to be eligible. The first postoperative 24 hours were divided into early (0−6 hours) and late (6–24 hours) time periods, and we collected these data separately. RESULTS: A total of 1372 patients were included in the final analysis. Compared with a placebo, ramosetron reduced the incidence of early postoperative nausea (PON) (relative risk [RR] [95% confidence interval] 0.59 [0.47–0.73]: number needed to treat [NNT] [95% confidence interval] 6.0 [4.3–9.7]), late PON (RR 0.65 [0.49–0.85]: NNT 7.2 [4.6–16.6]), early postoperative vomiting (POV) (RR 0.48 [0.31–0.74]: NNT 14.8 [8.3–70.4]), and late POV (RR 0.50 [0.35–0.73]: NNT 12.3 [7.1–47.6]). Compared with ondansetron, ramosetron reduces early POV (RR 0.50 [0.28–0.90]: NNT 24.1 [10.7–98.0]) and late POV (RR 0.53 [0.34–0.81]: NNT 27.2 [12.0–102.0]) but not PON. CONCLUSIONS: Ramosetron has a significant effect for preventing PONV compared with a placebo, but less than that reported in previous analyses. Ramosetron also has statistically significant differences in preventing early and late POV compared with ondansetron, but the clinical significance may be questioned because the NNTs are large.

Role of nerve growth factor-tyrosine kinase receptor A signaling in paclitaxel-induced peripheral neuropathy in rats

The mechanisms underlying paclitaxel-induced peripheral neuropathy remain unknown. Nerve growth factor (NGF) is a representative neurotrophic factor that maintains neuronal function, promotes survival, and mediates neuropathic pain. We investigated expression levels of NGF and its receptors in the dorsal root ganglia (DRG) and spinal dorsal horn (DH) following paclitaxel treatment. Intraperitoneal (I.P.) administration of paclitaxel induced significant mechanical hypersensitivity and cold allodynia in rats, significantly increased the expression of NGF and its receptor tyrosine kinase receptor A (trkA) in the DRG, and increased NGF expression in the DH. In contrast, paclitaxel treatment did not alter the mRNA levels of NGF or its receptors in the DRG, DH, sciatic nerve, or hindpaw skin. Moreover, expression of NEDD4-2, a negative regulator of trkA, was significantly increased in the DRG of paclitaxel-treated rats. Intrathecal (I.T.) administration of the tyrosine kinase receptor inhibitor k252a significantly alleviated mechanical hypersensitivity in paclitaxel-treated rats. Our results suggest that NGF-trkA signaling is involved in mechanical allodynia in paclitaxel-induced neuropathy.

Protective effects of continuous positive airway pressure on a nonventilated lung during one-lung ventilation: A prospective laboratory study in rats.

BACKGROUNDThe use of one-lung ventilation (OLV) to facilitate intrathoracic surgery is a cause of lung injury. OBJECTIVEWe hypothesised that application of continuous positive airway pressure (CPAP) to a nonventilated lung during OLV would prevent alveolar hypoxia and blood flow shift from the nonventilated to the ventilated lung, thereby attenuating lung injury. DESIGNControlled animal study. SETTINGSUniversity laboratory. STUDY PARTICIPANTSAdult male Sprague–Dawley rats (n = 4 to 8 per group, depending on experiments). INTERVENTIONSRats were alternately assigned to one of two ventilation protocol groups: control and CPAP groups. Rats received 240 min of OLV followed by 240 min of two-lung reventilation (re-TLV). The nonventilated lungs of rats in the control group were collapsed during OLV whereas rats in the CPAP group received CPAP (5 cmH2O with 100% oxygen) to the nonventilated lungs. MAIN OUTCOME MEASURESPulmonary blood flow during OLV was measured by quantification of lung radioactivity after intravenous infusion of indium111-labelled macroaggregated albumin. Inflammatory cytokines in the lungs after 240 min of OLV, and after the subsequent 240 min of re-TLV were measured. Additionally, we measured lung wet-to-dry weight ratios after re-TLV. We also measured lung malondialdehyde levels after re-TLV as an indicator of reactive oxygen species produced by reoxygenation. RESULTSApplication of CPAP attenuated the pulmonary blood flow shift from the nonventilated to the ventilated lung. CPAP decreased the levels of IL-6, CXC chemokine ligand-1 and CC chemokine ligand-2 in both lungs after 240 min of OLV. CPAP also decreased CXC chemokine ligand-1 in the nonventilated lung and CC chemokine ligand-2 in both lungs after re-TLV. Moreover, wet-to-dry weight ratios of both lungs were decreased by application of CPAP. However, lung malondialdehyde concentrations were not affected by CPAP. CONCLUSIONSCPAP applied to the nonventilated lung during OLV suppresses blood flow shift and decreases inflammatory cytokines and water content in both lungs. Application of CPAP may attenuate lung injury during and after OLV.

Comparison between High- and Low-Cost Transmission of Tele-Anesthesia in Japan

Background We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US

Enhancement of glycolysis by inhibition of oxygen-sensing prolyl hydroxylases protects alveolar epithelial cells from acute lung injury

0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

A pilot study of tele-anaesthesia by virtual private network between an island hospital and a mainland hospital in Japan

Cellular bioenergetic failure caused by mitochondrial dysfunction is a key process of alveolar epithelial injury during acute respiratory distress syndrome (ARDS). Prolyl hydroxylases (PHDs) act as cellular oxygen sensors, and their inhibition activates hypoxia-inducible factor (HIF), resulting in enhanced cellular glycolytic activity, which could compensate for impaired mitochondrial function and protect alveolar epithelial cells from ARDS. Here, we evaluated the effects of pharmacological PHD inhibition with dimethyloxalylglycine (DMOG) on alveolar epithelial cell injury using in vitro and in vivo ARDS models. We established an in vitro model of alveolar epithelial injury mimicking ARDS by adding isolated neutrophils and LPS to cultured MLE12 alveolar epithelial cells. DMOG treatment protected MLE12 cells from neutrophil-LPS-induced ATP decline and cell death. Knockdown of HIF-1α or inhibition of glycolysis abolished the protective effect of DMOG, suggesting that it was exerted by HIF-1-dependent enhancement of glycolysis. Additionally, intratracheal DMOG administration to mice protected the alveolar epithelial barrier and improved arterial oxygenation, preventing ATP decline during LPS-induced lung injury. In summary, enhancement of glycolysis by PHD inhibition is a potential therapeutic approach for ARDS, protecting alveolar epithelial cells from bioenergetic failure and cell death.- Tojo, K., Tamada, N., Nagamine, Y., Yazawa, T., Ota, S., Goto, T. Enhancement of glycolysis by inhibition of oxygen-sensing prolyl hydroxylases protects alveolar epithelial cells from acute lung injury. FASEB J. 32, 2258-2268 (2018). www.fasebj.org.Cellular bioenergetic failure caused by mitochondrial dysfunction is a key process of alveolar epithelial injury during acute respiratory distress syndrome (ARDS). Prolyl hydroxylases (PHDs) act as cellular oxygen sensors, and their inhibition activates hypoxia‐inducible factor (HIF), resulting in enhanced cellular glycolytic activity, which could compensate for impaired mitochondrial function and protect alveolar epithelial cells from ARDS. Here, we evaluated the effects of pharmacological PHD inhibition with dimethyloxalylglycine (DMOG) on alveolar epithelial cell injury using in vitro and in vivo ARDS models. We established an in vitro model of alveolar epithelial injury mimicking ARDS by adding isolated neutrophils and LPS to cultured MLE12 alveolar epithelial cells. DMOG treatment protected MLE12 cells from neutrophil‐LPS‐induced ATP decline and cell death. Knockdown of HIF‐1α or inhibition of glycolysis abolished the protective effect of DMOG, suggesting that it was exerted by HIF‐1‐dependent enhancement of glycolysis. Additionally, intratracheal DMOG administration to mice protected the alveolar epithelial barrier and improved arterial oxygenation, preventing ATP decline during LPS‐induced lung injury. In summary, enhancement of glycolysis by PHD inhibition is a potential therapeutic approach for ARDS, protecting alveolar epithelial cells from bioenergetic failure and cell death.— Tojo, K., Tamada, N., Nagamine, Y., Yazawa, T., Ota, S., Goto, T. Enhancement of glycolysis by inhibition of oxygen‐sensing prolyl hydroxylases protects alveolar epithelial cells from acute lung injury. FASEB J. 32, 2258–2268 (2018). www.fasebj.org

Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.

We studied the use of tele-anaesthesia between Sado General Hospital (SGH) located on Sado Island and Yokohama City University Hospital (YCUH) located in mainland Japan. The two sites were connected via a virtual private network (VPN). We investigated the relationship between the bandwidth of the VPN and both the frame rate and the delay time of the tele-anaesthesia monitoring system. The tool used for communication between the two hospitals was free videoconferencing software (FaceTime), which can be used over Wi-Fi connections. We also investigated the accuracy of the commands given during teleanaesthesia: any commands from the anaesthetist at the YCUH that were not carried out for any reason, were recorded in the anaesthetic records at the SGH. The original frame rate and data rate at the SGH were 5 fps and approximately 18 Mbit/s, respectively. The frame rate at the transmission speeds of 1, 5 and 20 Mbit/s was 0.6, 1.6 and 5.0 fps, respectively. The corresponding delay time was 12.2, 4.9 and 0.7 s. Twenty-five adult patients were enrolled in the study and tele-anaesthesia was performed. The total duration of anaesthesia was 37 hours. All 888 anaesthetic commands were completed. There were 7 FaceTime disconnections, which lasted for 10 min altogether. Because no commands needed to be given during the FaceTime disconnection, the telephone was not used. The anaesthesia assistance system might form part of the solution to medical resource shortages.