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重症気管支喘息患者における上・下気道の好酸球性炎症とオマリズマブに対する反応の関連性
Get PDF新潟大学Niigata University博士（医学）Background: The anti-immunoglobulin E monoclonal antibody, omalizumab, is used to treat severe asthma and has the potential to ameliorate airway inflammation. However, the effect of omalizumab in ameliorating upper airway inflammation has not been fully elucidated. Objective: We investigated the association of upper and lower airway inflammation with the response to omalizumab treatment. Methods: We used the Global Evaluation of Treatment Effectiveness to assess the efficacy of omalizumab in treating 16 patients with severe asthma. We also investigated the symptom score, short-acting β-agonist inhaler use, pul-monary function, biomarkers, computed tomography scans, and nasal mucosa pathology at omalizumab initiation and after four months of treatment. Results: When the fraction of exhaled nitric oxide (FeNO) and the percentage of sputum eosinophil were used as indica-tors of lower airway inflammation, positive correlations were found between CD20 B-cell, mast cell, and eosinophil counts in the nasal mucosa. Improved asthma symptoms were observed in 12 of the 16 severe asthma cases. The FeNO and eosinophil levels in the nasal tissue, prior to the administration of omalizumab were predictors of the response to asthma treatment. Conclusions: These findings suggest heterogeneity among people with severe asthma. In addition, the phenotype associated with response to omalizumab, leading to improvement in asthma symptoms, comprises upper airway eosinophilia and high FeNO levels.新大博（医）第1833
多発同時性腫瘍を認めたリンチ症候群関連子宮体癌におけるクローンの起源とゲノム多様性 : MLH1 p.L582H の病原性の確立
Get PDF新潟大学Niigata University博士（医学）Lynch syndrome-associated endometrial cancer patients often present multiple syn-chronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovar-ian metastasis. Her family history suggested Lynch syndrome, and genetic testing iden-tified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer ini-tiation. All tumors shared a portion of somatic mutations with high mutant allele fre-quencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones origi-nating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diver-sity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.Takahashi K, Yachida N, Tamura R, et al. Clonal origin and genomic diversity in Lynch syndrome-associated endometrial cancer with multiple synchronous tumors: Identification of the pathogenicity of MLH1 p.L582H. Genes Chromosomes Cancer. 2024; 63(3):e23231. doi:10.1002/gcc.23231新大院博（医）第1214
Contrast sensitivity test for Primary Open Angle Glaucomatous eyes
Get PDF新潟大学Niigata University博士（医学）目的 広義原発開放隅角緑内障(Primary Open Angle Glaucoma, 以下 POAG) 眼に対し、コントラスト感度(contrast sensitivity, 以下 CS) を測定し、視野障害早期・中期群と後期群の2群間で比較した。 方法 60 歳未満のPOAG 眼 109 例 109 眼に対して、コントラストグレアテスター2000 （以下 CGT 2000，タカギセイコー）を用いて明所条件(lOOcd) 、薄暮条件(lOcd) でのコントラスト感度を測定した。ハンフリー視野 (Humphrey field analyzer, 以下 HFA) 24-2、10-2 SITA standard の mean deviation (MD) 値で—12dB 以上とそれ未満の眼でそれぞれ視野障害早期・中期群（合わせて前期群とする）と後期群の 2 群に分け、CS の測定結果を群間で比較、検討した。 結果 HFA24-2 で値が≧—12dB（前期群）と<-12dB（後期群）のlog CS の平均を群間で比較すると、p 値は明所条件の視標サイズ6.3゜で p=0.009、4゜で p=0.028、2.5゜で p=0.028、1.6°で p=0.023、1゜で p=0.039、0.64゜ で p=0.011 であった。薄暮条件では視標サイズ 6.3゜で p=0.00038、4゜で p=0.0037、2.5゜で p=0.021、1.6゜で p=0.067、1゜で p=0.071、0.64゜ で p=0.448 であり、薄暮条件の視標サイズ1.6゜以下での測定を除き、統計学的な有意差を認めた。 HFAl0-2 でMD 値が≧—12dB（前期群）と<-12dB （後期群）のlogCS の平均を群間で比較すると、明所条件の視標サイズ6.3゜ で p=0.000021、4゜で p=0.000046、2.5゜で p=0.00018、1.6°で p=0.00013、1゜で p=0.00019、0.64゜で p=0.000018 であった。簿暮条件では視標サイズ6.3°で p=0.00000036、4゜で p=0.000029、2.5 で p=0.0015、1.6゜で p=0.024、1゜で p=0.0035、0.64゜で p=0.0043 であり、全ての視標サイズで前期群と後期群の間に統計学的な有意差を認めた。 結論 POAG 眼の CS は明所、薄暮のいずれの条件においても、視野障害前期群に対して後期群で低下していた。新大院博（医）第1219
高齢女性の変形性膝関節症における三次元的姿勢変化が立位下肢全長X線評価に与える影響
Get PDF新潟大学Niigata University博士（医学）Background: Long-leg frontal radiographs of the lower extremities are used to assess knee osteoarthritis. Given the three-dimensional (3D) nature of alignment changes in osteoarthritis, postural alterations in the femur and tibia extend beyond the coronal plane (in-plane) to include the transverse and sagittal planes (out-of-plane). This study investigates the impact of these out-of-plane factors on in-plane knee alignment parameters observed in frontal radiographs. Methods: A total of 97 osteoarthritic knees in women were examined. Using a 3D-to-two-dimensional (2D) image matching technique, we evaluated the 3D postures of the femur and tibia in the standing position as viewed from frontal radiographs in the world coordinate system. Statistical analyses were conducted to explore associations between these 3D postures and 2D alignment parameters obtained from frontal radiographs under identical conditions. Findings: The femur exhibited a medial inclination of 2.7 degrees, a posterior inclination of 3.9 degrees, and an internal rotation of 4.2 degrees, whereas the tibia showed a lateral inclination of 6.4 degrees, an anterior inclination of 6.7 degrees, and an internal rotation of 6.7 degrees. Both coronal and rotational postures of femur and tibia influenced the hip-knee-ankle angle, mechanical axis percentage, and medial proximal tibial angle. However, only coronal factors of tibia impacted tibial joint line obliquity. Interpretation: Attention should be paid to the potential impact of the out-of-plane postures of the femur and tibia on parameters assessed in plain frontal radio graphs of the lower extremities.Kazutaka Otani, Takashi Sato, Koichi Kobayashi, Tomoharu Mochizuki, Osamu Tanifuji, Ryota Katsumi, Hiroyuki Kawashima,
Effects of three-dimensional femur and tibia postures on the parameters of standing long-leg radiographs for osteoarthritic knees in elderly female subjects,
Clinical Biomechanics,
Volume 117,
2024,
106297,
ISSN 0268-0033,
https://doi.org/10.1016/j.clinbiomech.2024.106297.
(https://www.sciencedirect.com/science/article/pii/S0268003324001293)新大院博（医）第1221
閉塞性睡眠時無呼吸症候群患者における鼻腔通気度計測による鼻腔抵抗と持続気道陽圧呼吸療法のアドヒアランスの関係
Get PDF新潟大学Niigata University博士（医学）Nasal breathing disorders are associated with obstructive sleep apnea (OSA) syndrome and influence the availability of continuous positive airway pressure (CPAP) therapy. However, information is scarce about the impact of nasal resistance assessed by rhinomanometry on CPAP therapy. This study aimed to examine the relationship between CPAP adherence and nasal resistance evaluated by rhinomanometry, and to identify clinical findings that can affect adherence to CPAP therapy for patients with OSA. This study included 260 patients (199 men, 61 women; age 58 [interquartile ranges (IQR) 50–66] years) with a new diagnosis of OSA who underwent rhinomanometry (before, and 1 and 3 months after CPAP introduction) between January 2011 and December 2018. CPAP use was recorded, and the good and poor CPAP adherence groups at the time of patient registration were compared. Further-more, those with improved and unimproved pre-CPAP high rhinomanometry values were also compared. Their apnea-hypopnea index (AHI) by polysomnography at diagnosis was 45.6 (IQR 33.7–61.6)/hour, but the residual respiratory event (estimated AHI) at enrollment was 2.5 (IQR 1.4–3.9)/hour and the usage time was 318 (IQR 226–397) minutes, indicating that CPAP was effective and adherence was good. CPAP adherence was negatively corre-lated with nasal resistance (r = -0.188, p = 0.002). The participants were divided into good (n = 153) and poor (n = 107) CPAP adherence groups. In the poor adherence group, rhinoma-nometry values before CPAP introduction were worse (inspiration, p = 0.003; expiration, p = 0.006). There was no significant difference in patient background when comparing those with improved (n = 16) and unimproved (n = 12) pre-CPAP high rhinomanometry values. How-ever, CPAP usage time was significantly longer in the improved group 1 month (p = 0.002) and 3 months (p = 0.026) after CPAP introduction. The results suggest that nasal resistance evaluated by rhinomanometry is a useful predictor of CPAP adherence, and that improved rhinomanometry values may contribute to extending the duration of CPAP use.Fujito N, Ohshima Y, Hokari S, Takahashi A, Nagai A, et al. (2023) The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome. PLOS ONE 18(3): e0283070. https://doi.org/10.1371/journal.pone.0283070新大博（医）第1834
