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UBL3 interacts with alpha-synuclein in cells and the interaction is downregulated by the EGFR pathway inhibitor osimertinib
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Tubulin polyglutamylation by TTLL1 and TTLL7 regulate glutamate concentration in the mice brain
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Stomach, liver, kidney and skeletal muscle autoregulation evaluated by near-infrared spectroscopy in a swine model
No full textPurpose: Different organs have different autoregulatory capacities for blood pressure changes and/or circulatory volume changes. This study assessed the autoregulation of the stomach, liver, kidney and skeletal muscle, under baseline, hypovolemic, and post-fluid-resuscitation conditions using near-infrared spectroscopy (NIRS).
Methods: Ten pigs (bodyweight 24.5 ± 0.5kg) were anesthetized with 2.5% isoflurane and administered 0.5, 1, 2 and 5μg kg-1 min-1 of phenylephrine at 10-min intervals, followed by similar stepwise infusion of sodium nitroprusside (SNP) to induce a wide range of mean arterial pressures (MAPs). A 600-ml bleed was induced to create the hypovolemic condition, and only phenylephrine was re-administered. Hydroxyethyl starch (600ml) was infused to create the post-fluid-resuscitation condition, and phenylephrine and SNP were re-administered. Average relationships between mean arterial pressure (MAP) and each tissue oxygenation index (TOI) were assessed, and the individual relationships were evaluated based on the correlation coefficients between MAP and TOI during each vasoactive drug infusion.
Results: Based on the evaluation using each TOI as a substitute of blood flow, the kidney autoregulation was robust, similar to muscle, but had a prominent lower limit. The stomach had weaker autoregulation than the kidney and muscle. The liver had no autoregulation. The kidney TOI showed 2-fold greater changes in response to volume condition changes than the stomach and liver TOIs.
Conclusions: In our NIRS-based assessment of autoregulatory capacity, the liver oxygenation is highly blood pressure dependent, and the kidney is highly susceptible and the skeletal muscle is highly tolerable to low blood pressure and volume loss.journal articl
Relationship between the femoral and tibial component positions and postoperative knee range of motion after posterior-stabilized total knee arthroplasty in varus-aligned knees
No full textBackground:
This study aimed to evaluate the relationship between the femoral and tibial component positions and postoperative knee range of motion after posterior-stabilized total knee arthroplasty (TKA).
Patients:
Forty-four patients (48 knees in total: 9 men, 9 knees; 35 women, 39 knees) who underwent posterior-stabilized TKA using a navigation system were included.
Methods:
The femoral and tibial component positions were measured from the preoperative and postoperative computed tomography data with three-dimensional evaluation software. We investigated the relationship between the knee range of motion, including extension restriction and maximum flexion angles at 2 years postoperatively, and the femoral and tibial component positions.
Results:
Patients with knee extension restriction of 10° or more at 2 years postoperatively showed greater posterior flexion position of the tibial component than those with knee extension restriction less than 10° (6.2° and 3.9°, respectively, p=0.018). The postoperative knee flexion angle was positively associated with the internal rotational position of the femoral component (p=0.032, 95% confidence interval: 0.105−2.178). Patients with a knee flexion angle more than 120° at 2 years postoperatively had greater internal rotational position of the femoral component than those with 120° or less (5.2° and 1.5°, respectively, p=0.002).
Conclusions:
After posterior-stabilized TKA, the 28 postoperative knee extension restriction angle was associated with the posterior flexion position of the tibial component, and the knee flexion angle was positively related to the internal rotational position of the femoral component.journal articl
Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Patients with colorectal cancers (CRCs) generally exhibit improved survival through intensive lymph node (LN) dissection. However, recent progress in cancer immunotherapy revisits the potential importance of regional LNs, where T cells are primed to attack tumor cells. To elucidate the role of regional LN, we investigated the immunological status of nonmetastatic regional LN lymphocytes (LNLs) in comparison with those of the tumor microenvironment (tumor-infiltrating lymphocytes; TILs) using flow cytometry and next-generation sequencing. LNLs comprised an intermediate level of the effector T cell population between peripheral blood lymphocytes (PBLs) and TILs. Significant overlap of the T cell receptor (TCR) repertoire was observed in microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) CRCs with high tumor mutation burden (TMB), although limited TCRs were shared between nonmetastatic LNs and primary tumors in microsatellite stable/MMR proficient (MSS/pMMR) CRC patients with low TMB. In line with the overlap of the TCR repertoire, an excessive LN dissection did not provide a positive impact on long-term prognosis in our MSI-H/dMMR CRC cohort (n=130). We propose that regional LNs play an important role in antitumor immunity, particularly in MSI-H/dMMR CRCs with high TMB, requiring care to be taken regarding excessive nonmetastatic LN dissection in MSI-H/dMMR CRC patients.doctoral thesi
Comparison of operative outcomes between monopolar and bipolar coagulation in hepatectomy: a propensity score-matched analysis in a single center
Get PDF浜松医科大学博士（医学）dotoral医学系研究科Background: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices.
Methods: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications.
Results: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275min; P=0.013) and intraoperative blood loss (487 vs. 790mL; P<0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P=0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P=0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2mm; P<0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881–16.827; P=0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096–31.825; P=0.039).
Conclusions: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.doctoral thesi
Siblings with free sialic acid accumulation disorder presenting with transient nystagmus with identified homozygous variant c.116G>A, p.(Arg39His) in SLC17A5
Get PDF遊離シアル酸蓄積症（ree sialic acid storage disorder : FSASD）は，膜輸送タンパクであるシアリン（sialin）をコードするSLC17Aの両アレルバリアントにより発症し，髄鞘低形成，発達遅滞などを引き起こす非常に稀なライソゾーム病である．症例は4歳2か月姉と2歳5か月弟の姉弟例．共に発達遅滞，特徴的顔貌，筋緊張低下を認めた．姉は生後1か月時に発症し乳児期に眼振が一過性に出現した．姉弟共に頭部MRIにて髄鞘形成不全，脳梁低形成，小脳虫部低形成を認めた．エクソーム解析によりSLC17A5に両親由来ホモ接合性バリアント c.116G>A, p.(Arg39His)を同定した．Arg39HisはFSASD患者の8割が持つArg39Cysと同じ位置の異なるアミノ酸置換である．SLC17A5は大脳白質形成不全症の原因として重要であり，エクソーム解析が診断に有用である．journal articl
Development of a simple and objective prognostication model for patients with advanced solid malignant tumors treated with immune checkpoint inhibitors: A pan-cancer analysis
Get PDFBackground Systemic therapy using immune checkpoint inhibitors (ICIs) has recently become prevalent in the treatment of patients with various types of advanced cancers; however, difficulties are still associated with predicting the outcomes of patients receiving ICIs due to heterogenous responses to these agents. Therefore, the objective of the present study was to develop a prognostic model for advanced cancer patients treated with ICIs.
Patients and methods This study retrospectively analyzed the impact of clinical parameters on overall survival (OS) in 329 patients with several advanced solid malignant tumors who received systemic therapy using ICIs.
Results The primary tumors of 329 patients were as follows: lung (n=89), kidney (n=70), urinary tract (n=52), skin (n=50), stomach (n=30), esophagus (n=21), and head and neck (n=17). Median OS after the introduction of ICIs was 17.3 months. Among the factors that correlated with OS in a univariate analysis, body mass index, C-reactive protein, hemoglobin, lymphocytes, and platelets were identified as independent predictors of OS in a multivariate analysis. Following the classification of patients into 3 groups based on positive numbers of these independent risk factors, median OS was not reached in the favorable risk group with 0 or 1 risk factor (n=76), 19.5 months in the intermediate-risk group with 2 or 3 risk factors (n=182), and 8 months in the poor risk group (n=71) with 4 or 5 risk factors.
Conclusions Although this is a simple and objective model, it may be used as a reliable tool to predict the outcomes of advanced cancer patients receiving ICIs across multiple tumor types.journal articl
肘部管症候群
Get PDF雑誌掲載タイトル：肘部管症候群の病態と治療肘部管症候群は手根管症候群 (CTS) に次いで高頻度にみられる絞扼性神経障害であり、原因としては変形性関節症 (OA)、ガングリオン、内、外反肘、滑車上肘筋、Struthers' arcade などが報告されている。女性に好発する手根管症候群と比較し、肘部管症候群の女性患者に遭遇することは少なく、また男性患者との比較では病態が異なる。男女とも主な病因はOAであるが、女性においてOAの割合は男性と比較し有意に少ない。しかしながら肘部管症候群の重症度に男女差は見られない。診断にはいうまでもなく理学所見が最も重要であり、確定診断には電気生理学的検査を用いる。手術は肘部管における尺骨神経の絞扼を確実に解除する事であり、変形性肘関節症が主たる原因である本邦では King変法や尺骨神経皮下前方移動術が行われる。journal articl