Fibrin-glue-soaked bioabsorbable felt patches effectively seal intraoperative intractable air leaks. Felt patch use may increase the risk of postoperative infection. It should be considered for use on patients with fistulas that cannot be controlled by direct closure or otherwise intraoperatively and who may potentially develop uncontrollable air leakage postoperatively.

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MECK: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MECK was defined as the minimal current needed to produce a change in K. MECK significantly (P < 0.001) correlated with the rate of change of systolic blood pressure during skin incision (ROCBP). Bland–Altman plot analysis using the predicted ROCBP calculated from MECK and the measured ROCBP showed that the prediction equation for ROCBP was highly accurate. This study showed the potential of MECK to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs.Main methods: An in vivo model of I/R injury was tested in control, mTOR +/+ , and mTOR +/-. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified.Biochemical and mitochondrial swelling assays were also performed. Key findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this 4 BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001).Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect.

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Background. We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells. Methods. We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC50; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t -test while a P < 0.05 was considered significant. Results. Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM ( P = 0.76 ) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively ( P = 0.83 ). In mutant RYR1, EC50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively ( P = 0.63 ) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively ( P = 0.73 ). Remimazolam and propofol increased intracellular Ca2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively ( P = 0.91 ) while those of propofol were 1.09 mM vs. 1.05 mM, respectively ( P = 0.84 ). Conclusions. The increase in intracellular Ca2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1-mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs.

Thymic cancer is a rare tumor, the optimal treatment of which remains controversial. The efficacy of induction therapy in thymic cancer is unclear. A 51-year-old man was diagnosed as having a poorly differentiated carcinoma of the thymus with lymph node metastasis (stage IVb according to the Masaoka staging system), through an echo-guided biopsy. The patient was administrered cisplatin (CDDP) combined with paclitaxel once per week for 4 weeks, under concurrent local radiation. Once a partial response was achieved, the residual tumor was completely resected, and bilateral mediastinal lymph nodes were dissected. Histopathological examination of the resected specimen showed no evidence of viable malignant cells. At present, 15 months after surgery, the patient is doing well and shows no signs of recurrence. This case demonstrates that induction chemoradiotherapy with CDDP and paclitaxel may be well tolerated and useful for patients with advanced thymic cancer.

Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease.

Background Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.