Shiga University of Medical Science Repository BI WAKO / 滋賀医科大学機関リポジトリ
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    変形性膝関節症患者における術前血清アルブミン値が人工膝関節全置換術後の歩行機能及び入院期間に与える影響

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    滋賀医科大学修士(看護学)application/pdfThesis or Dissertation令和4年度thesi

    Immune-related aseptic meningitis diagnosed by Cube FLAIR on enhanced magnetic resonance imaging for a lung cancer patient administered atezolizumab: A case report

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    application/pdfImmune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as neurological toxicity. A 46-year-old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth-line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)-enhanced Cube fluid-attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd-enhanced Cube FLAIR sequence has the unique ability to reveal immune-related aseptic meningitisJournal Articlejournal articl

    Off-Pump Bilateral Skeletonized Internal Thoracic Artery Grafting in Octogenarians.

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    application/pdfBackground: We compared postoperative outcomes in octogenarians who underwent off-pump isolated coronary artery bypass grafting for multivessel disease using either skeletonized bilateral or single internal thoracic artery (ITA).Methods and Results: Among 1,532 patients who underwent isolated coronary artery bypass grafting between 2002 and 2021, 173 octogenarians were analyzed retrospectively. After inverse probability of treatment weighting, we found no statistically significant difference regarding patients' preoperative characteristics. No patient experienced deep sternal wound infection. More patients in the single than bilateral ITA group died within 30 days after surgery (5.0% vs. 0%, respectively; P=0.003). The mean follow-up duration was 4.2 years. At 5 years, the freedom from overall death following bilateral versus single ITA grafting was 78.2% and 53.7%, respectively (log-rank test, P=0.003), and freedom from major adverse cardiac and cerebrovascular events (MACCE) was 67.9% and 44.8% respectively (log-rank test, P=0.002). In multivariable Cox models, bilateral ITA grafting was significantly associated with a lower risk of overall death (hazard ratio [HR] 0.555; 95% confidence interval [CI] 0.342-0.903; P=0.018) and MACCE (HR 0.586; 95% CI 0.376-0.913; P=0.018).Conclusions: Compared with single ITA grafting, off-pump skeletonized bilateral ITA grafting is associated with lower rates of overall death and MACCE in octogenarians undergoing CABG and does not increase the risk of deep sternal wound infection.Journal Articlejournal articl

    Nuclear Expression of TDP-43 Is Linked with Morphology and Ubiquitylation of Cytoplasmic Aggregates in Amyotrophic Lateral Sclerosis

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    The transactive response DNA-binding protein of 43 kDa (TDP-43) is a pathological protein of amyotrophic lateral sclerosis (ALS). TDP-43 pathology is characterized by a combination of the cytoplasmic aggregation and nuclear clearance of this protein. However, the mechanisms underlying TDP-43 pathology have not been fully clarified. The aim of this study was to evaluate the relationships between the expression level of nuclear TDP-43 and the pathological properties of cytoplasmic aggregates in autopsied ALS cases. We included 22 consecutively autopsied cases with sporadic TDP-43-related ALS. The motor neuron systems were neuropathologically assessed. We identified 790 neurons with cytoplasmic TDP-43 inclusions from the lower motor neuron system of included cases. Nuclear TDP-43 disappeared in 84% (n = 660) and expressed in 16% (n = 130) of neurons with cytoplasmic inclusions; the former was defined as TDP-43 cytoplasmic immunoreactivity (c-ir), and the latter was defined as nuclear and cytoplasmic immunoreactivity (n/c-ir). Morphologically, diffuse cytoplasmic inclusions were significantly more prevalent in TDP-43 n/c-ir neurons than in c-ir neurons, while skein-like and round inclusions were less prevalent in n/c-ir neurons. The cytoplasmic inclusions of TDP-43 n/c-ir neurons were phosphorylated but poorly ubiquitylated when compared with those of c-ir neurons. TDP-43 n/c-ir neurons became less dominant than the c-ir neurons among cases with a prolonged disease duration. The expression level of nuclear TDP-43 was significantly lower in n/c-ir neurons than in normal neurons without cytoplasmic inclusions. Our results indicate that the maturation of cytoplasmic TDP-43 inclusions correlates with the depletion of nuclear TDP-43 in each affected neuron. This finding supports the view that an imbalance between nuclear and cytoplasmic TDP-43 may be an essential pathway to TDP-43 pathology.journal articl

    Exploratory study on quantitative assessment of skin hardness in patients with systemic sclerosis using SOFTGRAM

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    Objectives: There is a lack of quantitative and objective methods for measuring skin hardness. This study aimed to verify whether SOFTGRAM, a device that can measure elastic modulus using the Hertz elastic contact theory, could be used to evaluate skin hardness in systemic sclerosis (SSc). Methods: Skin score according to the modified Rodnan total skin thickness score and elastic modulus of the skin using SOFTGRAM were measured for 20 patients with SSc and 20 healthy controls on 8 parts of the body, both of the cheeks, forearms, fingers, and hands. Five observers shared to measure skin score 320 times (40 participants × 8 parts). Elastic modulus was measured 1600 times (40 participants × 8 parts × 5 times each). As an additional examination to compare differences between observers, the skin score of another healthy control was measured 40 times (5 observers × 8 parts). Elastic modulus was measured 200 times (5 observers × 8 parts × 5 times each). Results: There was a significant correlation between elastic modulus and skin score (correlation coefficient=0.67, p<0.001) and a significant difference in elastic modulus (8 parts: healthy controls vs. limited cutaneous SSc vs. diffuse cutaneous SSc: 22.6±15.7 vs. 32.0±27.7 vs. 44.8±39.8, p<0.001). Intraobserver reliabilities were sufficient in 6 out of 7 observers; however, interobserver was less satisfactory. Conclusions: This study showed the practicality of SOFTGRAM as an accurate measurement method of skin hardness but also revealed points to be improved. More studies are needed to find an accurate measurement method of skin hardness.journal articl

    Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes

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    Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of β-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of β-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to β-cell ratio and the number of apoptotic β-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic β-cells apoptosis.journal articl

    キョウブ ダイドウミャク ジンコウ ケッカン チカン ジュツゴ ニ カッケツ トケツ オ キタシタ サイシュジュツ ショウレイ ノ セイセキ

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    【緒言】 胸部大動脈疾患に対する人工血管置換術後に、喀血・吐血を来して再手術を要した症例の背景、予後を報告する。 【症例】 当院で2012年1月から2020年12月までに、喀血・吐血を主訴に胸部大動脈手術を行った24例中、人工血管置換術後の19例(喀血11、吐血8)を対象とした。 【結果】 年齢中央値73歳(49 - 88歳)、男性12例、女性7例、17例は緊急で手術を行った。初回手術からの間隔は中央値435日(55 - 1883日)であり、初回手術は上行置換1例、下行置換7例、弓部置換11例であった。手術適応は人工血管感染11例、仮性動脈瘤7例、急性大動脈解離1例であった。感染症例の内、9例に大動脈食道瘻を認めた。今回手術は、下行置換6例、胸腹部置換1例、弓部置換3例、ステントグラフト8例、自己弁温存基部置換術1例であった。全体の在院死亡は6例(32%)、生存者の術後滞在期間の中央値は101日であった。大動脈食道瘻を来した症例のうち6例は、2期的に食道抜去も施行し、その在院死亡は33%であった。一方、食道抜去を施行しなかった3例の在院死亡は67%であった。感染の有無で2群に分け検討したところ、在院死亡に統計学的有意差は認めなかった(p=0.147)。Kaplan-Meier法による全体の3年生存率は22.8%と不良であり、感染を認めた群では2年生存率9%と極めて不良であった。 【結論】 胸部人工血管置換後に喀血・吐血を来した症例の中でも、人工血管感染を生じた症例の予後は極めて不良であった。特に大動脈食道瘻を認めた場合は、食道抜去が必要であると考えられる。Introduction: We report the conditions and outcomes of patients suffering thoracic aortic disease, who developed hematemesis and hemoptysis and required reoperation. Patients: From January 2012 to December 2020, 19 patients (11 hemoptysis, 8 hematemesis) who had previous thoracic aortic surgery required reoperation with the main complaint of hemoptysis and hematemesis. Results: The median age was 71.5 years; there were 7 females, and 17 urgent cases. The median interval since the previous surgery was 435 days (55 to 1883 days), and the previous surgeries were 1 ascending aorta replacement, 7 descending aorta replacements, and 11 total arch replacements. The indications for reoperation were infection in 11 cases, pseudoaneurysm in 7 cases, and acute aortic dissection in 1 case. Aortoesophageal fistula was found in 9 of the infected cases. The surgical actions were 6 descending aorta replacements, 1 thoracoabdominal aorta replacement, 3 total arch replacements, 8 stent grafts, and 1 valve-sparing root reconstruction. Only one patient, who suffered aortic rupture due to dissection, died within 30 days. Six of the cases with aortoesophageal fistula also underwent esophagectomy in the second phase. There were 6 in-hospital mortality cases (32%), and the median length of stay after surgery for survivors was 101 days. The patients were divided into two groups according to the presence of infection, but the difference in-hospital mortality (infection (-): 13%, (+): 45%, p = 0.147) was not statistically significant. The 3-year survival rate by the Kaplan-Meier method was 23% overall, but the 2-year survival rates were 9% in the infected group and 53% in the non-infected group (Log-rank p= 0.167). Conclusion: Among the patients developing hemoptysis and hematemesis after previous thoracic aortic surgery, the cases of graft infection had extremely poor prognosis. Especially when aortoesophageal fistula is found, it is necessary to consider esophagectomy immediately.departmental bulletin pape

    Successful management of a large lingual foregut duplication cyst with an ex-utero intrapartum treatment procedure

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    application/pdfForegut duplication cysts are rare congenital choristomas that sometimes cause feeding and respiratory problems, depending on their size and location. Prenatal ultrasonography revealed a fetus with a large oral cystic mass and polyhydramnios. Differential diagnoses included ranula, lymphangioma, and thyroglossal duct cysts. A multidisciplinary fetal care team devised an airway management plan. We performed ex-utero intrapartum treatment (EXIT) because the origin and patency of the fetal airway could not be confirmed using fetal magnetic resonance imaging. At delivery, a lingual cyst occupied the oral cavity and protruded from the mouth. Oral intubation was performed after the aspiration of the cyst during the EXIT. On day 16, the cyst was completely excised. Histopathological examination revealed a foregut duplication cyst lined by the respiratory and gastric epithelium. Lingual foregut duplication cysts pose a risk for airway obstruction. For prenatally diagnosed cases, coordination of a multidisciplinary fetal care team and early discussions can optimize the plan for prenatal management, including the EXIT procedure.Journal Articlejournal articl

    Essential Roles of Exocyst Complex Component 3-like 2 on Cardiovascular Development in Mice

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    滋賀医科大学博士(医学)application/pdfAngiogenesis is a process to generate new blood vessels from pre-existing vessels and to maintain vessels, and plays critical roles in normal development and disease. However, the molecular mechanisms underlying angiogenesis are not fully understood. This study examined the roles of exocyst complex component (Exoc) 3-like 2 (Exoc3l2) during development in mice. We found that Exoc3l1, Exoc3l2, Exoc3l3 and Exoc3l4 are expressed abundantly in endothelial cells at embryonic day 8.5. The generation of Exoc3l2 knock-out (KO) mice showed that disruption of Exoc3l2 resulted in lethal in utero. Substantial numbers of Exoc3l2 KO embryos exhibited hemorrhaging. Deletion of Exoc3l2 using Tie2-Cre transgenic mice demonstrated that Exoc3l2 in hematopoietic and endothelial lineages was responsible for the phenotype. Taken together, these findings reveal that Exoc3l2 is essential for cardiovascular and brain development in mice.Thesis or Dissertation令和4年度doctoral thesi

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