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Preoperative prognostic nutritional index as a predictive factor for medical complication after cervical posterior decompression surgery: a multicenter study
浜松医科大学博士(医学)doctoral医学系研究科thesi
Development and validation of the optimal circumferential resection margin in pathological T3 esophageal cancer: a multicenter retrospective study
浜松医科大学博士(医学)doctoral医学系研究科thesi
Effect of hypoxia on pulmonary endothelial cells from bleomycin-induced pulmonary fibrosis model mice
浜松医科大学博士(医学)dotoral医学系研究科Pulmonary fibrosis is a progressive and fatal disorder characterized by dysregulated repair after recurrent injury. Destruction of the lung architecture with excess extracellular matrix deposition induces respiratory failure with hypoxia and progressive dyspnea. The impact of hypoxia on pulmonary endothelial cells during pulmonary fibrogenesis is unclear. Using a magnetic-activated cell sorting system, pulmonary endothelial cells were isolated from a mouse model of pulmonary fibrosis induced by intratracheally administered bleomycin. When endothelial cells were exposed to hypoxic conditions, a hypoxia-inducible factor (HIF)-2α protein was detected in CD31- and α-smooth muscle actin (SMA)-positive cells. Levels of plasminogen activator inhibitor 1, von Willebrand factor, and matrix metalloproteinase 12 were increased in endothelial cells isolated from bleomycin-treated mice exposed to hypoxic conditions. When endothelial cells were cultured under hypoxic conditions, levels of fibrotic mediators, transforming growth factor- and connective tissue growth factor, were elevated only in endothelial cells from bleomycin-treated and not from saline-treated lungs. The increased expression of α-SMA and mesenchymal markers and collagen production in bleomycin- or hypoxia-stimulated endothelial cells were further elevated in endothelial cells from bleomycin-treated mouse lungs cultured under hypoxic conditions. Exposure to hypoxia damaged endothelial cells and enhanced fibrogenesis-related damage in bleomycin-treated pulmonary endothelial cells.doctoral thesi
Associations between prefrontal PI (16:0/20:4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain
浜松医科大学博士(医学)doctoral医学系研究科Background: Though various mechanisms have been proposed for the pathophysiology of schizophrenia, the full extent of these mechanisms remains unclear, and little is known about the relationships among them. We carried out trans-omics analyses by comparing the results of the previously reported lipidomics, transcriptomics, and proteomics analyses; all of these studies used common post-mortem brain samples.
Methods: We collected the data from three aforementioned omics studies on 6 common post-mortem samples (3 schizophrenia patients and 3 controls), and analyzed them as a whole group sample. Three correlation analyses were performed for each of the two of three omics studies in these samples. In order to discuss the strength of the correlations in a limited sample size, the p-values of each correlation coefficient were confirmed using the Student’s t-test. In addition, partial correlation analysis was also performed for some correlations, to verify the strength of the impact of each factor on the correlations.
Results: The following three factors were strongly correlated with each other: the lipid level of phosphatidylinositol (PI) (16:0/20:4), the amount of TNC mRNA, and the quantitative signal intensity of APOA1 protein. PI (16:0/20:4) and TNC showed a positive correlation, while PI (16:0/20:4) and APOA1, and TNC and APOA1 showed negative correlations. All of these correlations reached at p<0.01. PI (16:0/20:4) and TNC were decreased in the prefrontal cortex of schizophrenia samples, while APOA1 was increased. Partial correlation analyses among them suggested that PI (16:0/20:4) and TNC have no direct correlation, but their relationships are mediated by APOA1.
Conclusion: The current results suggest that these three factors may provide new clues to elucidate the relationships among the candidate mechanisms of schizophrenia, and support the potential of trans-omics analyses as a new analytical method.doctoral thesi
A convenient online desalination tube coupled with mass spectrometry for the direct detection of iodinated contrast media in untreated human spent hemodialysates.
浜松医科大学博士(医学)doctoral医学系研究科Background
Mass spectrometry (MS) analysis using direct infusion of biological fluids is often problematic due to high salts/buffers. Iodinated contrast media (ICM) are frequently used for diagnostic imaging purposes, sometimes inducing acute kidney injury (AKI) in patients with reduced kidney function. Therefore, detection of ICM in spent hemodialysates is important for AKI patients who require urgent continuous hemodiafiltration (CHDF) because it allows noninvasive assessment of the patient’s treatment. In this study, we used a novel desalination tube before MS to inject the sample directly and detect ICM.
Methods
Firstly, spent hemodialysates of one patient were injected directly into the electrospray ionization (ESI) source equipped with a quadrupole time-of-flight mass spectrometer (Q-TOF MS) coupled to an online desalination tube for the detection of ICM and other metabolites. Thereafter, spent hemodialysates of two patients were injected directly into the ESI source equipped with a triple quadrupole mass spectrometer (TQ-MS) connected to that online desalination tube to confirm the detection of ICM.
Results
We detected iohexol (an ICM) from untreated spent hemodialysates of the patient-administered iohexol for computed tomography using Q-TOF MS. Using MRM profile analysis, we have confirmed the detection of ICM in the untreated spent hemodialysates of the patients administered for coronary angiography before starting CHDF. Using the desalination tube, we observed approximately 178 times higher signal intensity and 8 times improved signal-to-noise ratio for ioversol (an ICM) compared to data obtained without the desalination tube. This system was capable of tracking the changes of ioversol in spent hemodialysates of AKI patients by measuring spent hemodialysates.
Conclusion
The online desalination tube coupled with MS showed the capability of detecting iohexol and ioversol in spent hemodialysates without additional sample preparation or chromatographic separation. This approach also demonstrated the capacity to monitor the ioversol changes in patients’ spent hemodialysates.doctoral thesi
Intraarterial urokinase for thrombus migration after mechanical thrombectomy for large vessel ischemic stroke
[Background] Achieving rapid and complete reperfusion is the ultimate purpose for ischemic stroke with large vessel occlusion (LVO). Although mechanical thrombectomy (MT) had been a proverbially important procedure, medium vessel occlusion (MeVO) with thrombus migration can sporadically occur after MT. Moreover, the safe and effective approach for such had been unknown. We reported thrombolysis with intraarterial urokinase for MeVO with thrombus migration after MT.
[Methods] We included 122 patients who were treated by MT with LVO stroke at our institution between April 2019 and March 2021. Of 26 patients (21.3%) who developed MeVO with thrombus migration after MT, 11 (9.0%) underwent additional MT (MT group) and 15 (12.3%) received intraarterial urokinase (UK group). The procedure time; angiographically modified Treatment in Cerebral Ischemia Scale (mTICI); functional independence, which was defined as modified Rankin Scale 0–2, on day 30 or upon discharge; and symptomatic and asymptomatic intracerebral hemorrhage (ICH) were compared between the UK and MT groups.
[Results] The procedure time, mTICI, and asymptomatic ICH did not significantly differ between the groups. In the UK group, 8 of 15 (53.3%) patients obtained functional independence, and the functional independence rate was significantly higher in the UK group than in the MT group (p<0.05). Symptomatic ICH did not occur in the UK group, and its incidence was significantly smaller than that in the MT group (p<0.05).
[Conclusion] The results of this study suggest that intraarterial urokinase for MeVO with thrombus migration after MT may safely improve angiographic reperfusion.journal articl
Management of non-cerebral malperfusion complicating acute type A dissection
雑誌掲載タイトル:Management of noncerebral malperfusion complicating acute type A dissectionVital organ malperfusion in acute type A aortic dissection is associated with worse outcomes, especially when multiple organ systems are involved, and when coronary or mesenteric malperfusion is present. To achieve the two goals of central aortic repair and adequate and timely reperfusion, mechanism and organ-specific strategy in the methods and sequence of repair should be considered. For dynamic aortic malperfusion, reperfusion can be quickly achieved by femoral artery perfusion, and the fenestrated frozen elephant trunk operation, in which the proximal end of device is secured to zone 1 or 2 and distal 1 or 2 supra-aortic vessels are preserved by fenestration of the fabric, seems optimal as a method of central aortic repair. For coronary malperfusion, percutaneous coronary intervention before central aortic repair may have a role. However, it should be kept in mind that the door-to-unloading time is also important to reduce the area of myocardial infarction, and retrograde cardioplegia is not distributed to most of the right ventricle, which can be critical when right coronary malperfusion is present. Static mesenteric malperfusion should be addressed first, and second look laparotomy should not be hesitated after central aortic repair. The use of a hybrid operating room may be an optimal solution to achieve both goals.journal articl