The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer

BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens

Direct observation of the washboard noise of a driven vortex lattice in a high-temperature superconductor, Bi2Sr2CaCu2Oy

We studied the conduction noise spectrum in the vortex state of a high-temperature superconductor, Bi2Sr2CaCu2Oy, subject to a uniform driving force. Two characteristic features, a broadband noise (BBN) and a narrow-band noise (NBN), were observed in the vortex-solid phase. The origin of the large BBN was determined to be plastic motion of the vortices, whereas the NBN was found to originate from the washboard modulation of the translational velocity of the driven vortices. We believe this to be the first observation ofComment: 4 pages, 4 figures, to appear in Phys. Rev. Let

頭側延髄外腹側野におけるNeuregulin-1/ErbBシグナル系は降る圧系として血圧調節に関与する

Submitted by 愛 遠藤 ([email protected]) on 2013-07-11T05:22:18Z No. of bitstreams: 2 med2456.pdf: 325189 bytes, checksum: fb37944ccfb419dcf1eef3cf61422f0d (MD5) med2456_abstract.pdf: 155645 bytes, checksum: dd7e86348538eaa8323a97158dde35fb (MD5)Made available in DSpace on 2013-07-11T05:22:18Z (GMT). No. of bitstreams: 2 med2456.pdf: 325189 bytes, checksum: fb37944ccfb419dcf1eef3cf61422f0d (MD5) med2456_abstract.pdf: 155645 bytes, checksum: dd7e86348538eaa8323a97158dde35fb (MD5) Previous issue date: 2012-03-27医学系学府_医学<目的> Neureglin-1(NRG-1)は中枢神経系に存在しており、ErbB受容体に作用してシナプス機能、神経突起の成長、ニューロンやグリア細胞の生存に重要な役割を担っている。しかしながら、中枢神経系におけるNRG-1/ErbBシグナル系の機能的な役割および特に、主要な血管運動中枢である頭側延髄外腹側野 (RVLM)における血圧調節に関する役割は明らかではない。そこで、我々はRVLMにおけるNRG-1/ErbBシグナル系が血圧調節に関与しているかどうかについて検討した。<方法および結果>WistarラットにおいてRVLMへのNRG-1を微量投与すると血圧、心拍数および腎交感神経活動が低下した。対照的にErbB2もしくはErbB4阻害薬のRVLMへの微量投与は血圧、心拍数、腎交感神経活動は増加した。脳幹部におけるErbB2受容体の発現レベルはWistar-Kyoto (WKY)ラットに比べ、高血圧自然発症ラット (SHR)において著明に低下していた。NRG-1による降圧反応およびErbB2阻害薬による昇圧反応はWKYラットに比べSHRにおいて著明に減弱していた (p<0.05)。さらに、覚醒下のWKYラットにおいてRNA interferenceによるRVLMにおけるErbB2受容体の発現を抑制すると血圧、心拍数、尿中ノルエピネフリンの排泄量は著明に増加した (p<0.01)。 <結論> 以上の成績は、RVLMにおけるNRG-1/ErbBシグナル系は降圧作用および交感神経抑制作用を持つことを示唆する。RVLMにおけるNRG-1/ErbB2シグナル系の機能低下は高血圧の神経性機序に関与しているかもしれない

Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms

Background　Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. Methods　Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. Results　The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). Conclusions　Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates

Netrin-G/NGL complexes encode functional synaptic diversification

Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity

A scoring evaluation for the practical introduction of guideline‐directed medical therapy in heart failure patients

Abstract Aims The guideline‐directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial‐proven medications for every patient in the real world. Methods and results A simple GDMT score was created, according to the combination of GDMT drugs (renin–angiotensin system inhibitors, beta‐blockers, mineralocorticoid receptor antagonists, and sodium–glucose transporter 2 inhibitors) administration and their dosage (0–9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n = 1054] were retrospectively analysed (excluding those with in‐hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all‐cause death, HF readmission, and composite outcome (HF readmission and all‐cause death) (P < 0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis. Conclusions The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients

Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients’ clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients’ dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as &lt;60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan–Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p &lt; 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients’ calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship

Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients’ clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients’ dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients’ calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship

Impact of citrus fruit intake on the mental health of patients with chronic heart failure

Background: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. Methods: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). Results: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score > 10). The patients with PHQ-9 > 10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. Conclusions: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients. (C)2021 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved