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Prediction of postoperative complications after hepatectomy with dynamic monitoring of central venous oxygen saturation
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Background The usefulness of static monitoring using central venous pressure has been reported for anesthetic management in hepatectomy. It is unclear whether intra-hepatectomy dynamic monitoring can predict the postoperative course. We aimed to investigate the association between intraoperative dynamic monitoring and post-hepatectomy complications. Furthermore, we propose a novel anesthetic management strategy to reduce postoperative complication.
Methods From 2018 to 2021, 93 patients underwent hepatectomy at our hospital. Fifty-three patients who underwent dynamic monitoring during hepatectomy were enrolled. Flo Trac system was used for dynamic monitoring. The baseline central venous oxygen saturation (ScvO2) was defined as the average ScvO2 for 30 min after anesthesia induction. ScvO2 fluctuation (ΔScvO2) was defined as the difference between the baseline and minimum ScvO2. Postoperative complications were evaluated using the comprehensive complication index (CCI).
Results Patients with ΔScvO2 ≥ 10% had significantly higher CCI scores (0 vs. 20.9: p=0.043). In univariate analysis, patients with higher CCI scores demonstrated significantly higher preoperative C-reactive protein-to-lymphocyte ratio (7.51 vs. 24.49: p=0.039), intraoperative bleeding (105 vs. 581 ml: p=0.008), number of patients with major hepatectomy (4/45 vs. 3/8: p=0.028), and number of patients with ΔScvO2 ≥ 10% (11/45 vs. 6/8; p=0.010). Multivariate logistic regression analysis revealed that ΔScvO2 ≥ 10% (odds ratio: 9.53, p=0.016) was the only independent predictor of elevated CCI.
Conclusions Central venous oxygen saturation fluctuation during hepatectomy is a predictor of postoperative complications. Anesthetic management based on intraoperative dynamic monitoring and minimizing the change in ScvO2 is a potential strategy for decreasing the risk of post-hepatectomy complications.doctoral thesi
Alpha-synuclein interaction with UBL3 is upregulated by microsomal glutathione S-transferase 3, leading to increased extracellular transport of the alpha-synuclein under oxidative stress
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson’s disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases
Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation
Get PDF令和6年 浜松医科大学優秀論文賞：優秀論文賞
受賞者：伊藤 昌彦Background & Aims: Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.
Methods: The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry. Triglyceride accumulation and lipid droplet formation were studied in phospholipase A2 group 4C (PLA2G4C) knockout or overexpressing cells.
Results: Imaging mass spectrometry of the infected mouse model revealed increased lysophosphatidylcholine levels and decreased phosphatidylcholine levels in HCV-positive regions of the liver. Among the transcripts associated with phosphatidylcholine biosynthesis, upregulation of PLA2G4C mRNA was most pronounced following HCV infection. Activation of the transcription factor NF-jB and upregulation of c-Myc were important for activation of PLA2G4C transcription by HCV infection and expression of the viral proteins Core-NS2. The amount and size of lipid droplets were reduced in PLA2G4C-knockout cells. Inhibition of NF-jB or c-Myc activity suppressed lipid droplet formation in HCV-infected cells. HCV infection promoted the stabilization of lipid droplets, but this stability was reduced in PLA2G4C-knockout cells. Overexpression of PLA2G4C decreased the levels of phosphatidylcholine species in the lipid droplet fraction and led to lower levels of key factors involved in lipolysis (breakdown of triglycerides into glycerol and free fatty acids), such as ATGL, PLIN1 and ABHD5 on the lipid droplets.
Conclusions: HCV infection markedly increases PLA2G4C expression. This may alter the phospholipid composition of the lipid droplet membrane, leading to stabilization and enlargement of the droplets.journal articl
Enhancing cervical cancer cytology screening via artificial intelligence innovation
Get PDF令和6年 浜松医科大学論文賞：優秀論文賞（学生特別枠）
受賞者：栗田 佑希A double-check process helps prevent errors and ensures quality control. However, it may lead to decreased personal accountability, reduced effort, and declining quality checks. Introducing an artificial intelligence (AI)-based system in such scenarios could effectively address the risk of oversights. This study introduces an innovative AI-integrated workflow for cervical cytology screening that substantially improves efficiency and reduces the burden on cytologists. The AI model prioritizes cases for review based on anomaly scores and streamlines the first screening process to approximately 10 s per case. The model enhances the identification of high-risk cases via detailed microscopic observation, high anomaly scores cases, and a targeted review of low-score cases. The workflow highlights its capability for rapid, accurate, and less labor-intensive evaluations, demonstrating the potential to transform cervical cancer screening. This study highlights the importance of AI in modern medical diagnostics, particularly in areas with a high demand for accuracy and efficiency.journal articl
Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study
Get PDFAim: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy.
Methods: We enrolled patients with chronic hepatitis C who underwent DAA therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow-up when the absence of HCC was confirmed. Uni- and multi-variate Cox proportional hazard models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan–Meier method and differences between groups were assessed using the log-rank test.
Results: The final study cohort comprised 482 patients (median age, 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) were independent risk factors significantly associated with HCC development (P<0.001–0.04). The highest risk group included patients with both a history of HCC and the presence of HBP hypointense nodules without APHE (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively).
Conclusion: History of HCC and presence of HBP hypointense nodules without APHE were strong risk factors for HCC development following DAA therapy.journal articl
Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane
Get PDFPurpose: Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm. Methods: Male adult C57BL/6J mice were divided into eight groups (n=8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6–12 or ZT18–24). Mice were anesthetized for 6 hours using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n=8–9 each). Results: Phase shift after anesthesia at ZT6–12 using sevoflurane (-0.49 hour) was smaller compared with desflurane (-1.1 hour) and isoflurane (-1.4 hour) (p<0.05). Clock mRNA (ZT6–12, p<0.05) and Per2 mRNA (ZT18–24, p<0.05) expression were different between the groups after anesthesia. Conclusion: 0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm
Duration of Antibiotics for Common Pediatric Infectious Diseases
Get PDF抗菌薬の標準的な投与期間は経験則に基づいて設定されてきた．多くの場合は治療失敗を回避するために長めに設定されており，薬剤の長期投与によるデメリットは過少評価されてきた．近年，薬剤耐性菌対策の一環として，抗菌薬投与期間を短縮する試みが科学的に検証され，ランダム化比較試験や系統レビューの対象となっている．小児の一般的な感染症である，溶連菌咽頭炎，急性鼻副鼻腔炎，肺炎，尿路感染症については，有効性を損なうことなく従来の標準的な治療期間を短縮することが可能であることが確認され，各種ガイドラインにもこれが反映されつつある．その一方で，2歳未満の急性中耳炎に代表されるように，短期治療で再燃率が高まるリスク集団が存在し，適切な治療にあたっては，個別の評価が必要である．The standard length of antibiotic therapy has been empirically determined. In general, extensive coverage has been used to avoid treatment failures, and the risks of long-term antibiotics have been understated. The recent push to address antimicrobial resistance has resulted in scientific evaluation of antibiotic duration using randomized control trials and systematic reviews. Studies have shown that the current standard duration of antibiotics for common pediatric infectious diseases such as streptococcal pharyngitis, acute rhinosinusitis, pneumonia, and urinary tract infection can be reduced without compromising effectiveness, prompting changes in practice guidelines. In contrast, certain at-risk populations, such as children under the age of two with otitis media, experience recurrences with shorter antibiotic duration and require tailored evaluations for appropriate management.journal articl
Remarkable improvement in glucose management through SAP therapy in a patient with type 1 diabetes mellitus
Get PDF1型糖尿病（Type1 Diabetes Mellitus：T1DM）は，膵β細胞破壊によるインスリン欠乏を来たす疾患である．本邦でのT1DMの発症頻度は，1.4–2.2/10万人/年と比較的少ない．T1DM患者は，生涯に渡ってインスリン投与と血糖管理が必要となる．近年，糖尿病治療に関するデバイスが次々と登場し，インスリン治療方法の選択枝が広がり，新たな血糖コントロールの指標も登場してきている．
症例は10歳発症のT1DM患者．同級生にT1DMであることを知られたくないため，学校でインスリン皮下注射も自己血糖測定も十分できずに血糖コントロール不良であった．17歳時にリモコン操作可能なインスリンポンプを用いたSensor Augmented Pump（SAP）療法を導入することで良好な血糖コントロールが得られた．小児期発症T1DM患者は，罹病期間が非常に長期にわたるばかりでなく，成長とともに生活環境が大きく変化する．したがって患者毎に適した治療デバイスを選択し，良好な血糖コントロールを維持することが大切である．Type 1 diabetes mellitus (T1DM) is characterized by impaired insulin secretion due to β cell destruction. As a result, individuals with T1DM necessitate insulin therapy. In recent years, a variety of insulin treatment devices has emerged, coinciding with the development of innovative metrics for evaluating glucose status. We encountered a male adolescent patient who was diagnosed with T1DM at 10 years of age and administrated subcutaneous multiple-daily insulin injections (MDI). However, to maintain privacy regarding his T1DM status among classmates, the patient exhibited poor glucose control due to insufficient insulin injections and self-monitoring of blood glucose (SMBG). At 17 years of age, he was referred to our department to improve glucose management. At that time, the patient was solely engaged in once-daily injections of basal insulin (insulin degludec), with limited utilization of SMBG. His HbA1c level was 12.4%, and blood glucose levels were above 400 mg/dL. The introduction of the Sensor Augmented Pump (SAP), which utilizes a remotely controllable insulin pump, resulted in a remarkable improvement in glucose control. Twelve months later, his HbA1c had improved to 6.9% with a Time in Range (TIR) of 74%. Children with T1DM not only encounter an exceptionally extended prolonged duration of illness but also experience lifestyle changes as they grow. Therefore, the selection of treatment devices personalized for each patient is essential to maintain optimal glucose management.journal articl
Association of malnutrition and high bleeding risk with long-term prognosis in patients with acute coronary syndrome following percutaneous coronary intervention
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Expression of tumor suppressor FHIT is regulated by the LINC00173-SNAIL axis in human lung adenocarcinoma
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi