tbuckley/cabot-search huggingface dataset:
Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors
Authors: Di Chen, Gaopeng Li, Chunxia Ji, Qiqi Lu, Ying Qi, Chao Tang, Ji Xiong, Jian Hu, Fatma Betul Aksoy Yasar, Yan Zhang, Dave S B Hoon, Yu Yao, Liangfu Zhou
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Characterizing expression profiles of different immune checkpoint molecules are promising for personalized checkpoint inhibitory immunotherapy. Gliomas have been shown as potential targets for immune checkpoint inhibitors recently. Our study was performed to determine coexpression levels of two major B7 immune regulatory molecules programmed death ligand 1 (PD-L1) and B7-H4, both of which have been demonstrated to inhibit antitumor host immunity in gliomas. Methods We assessed tumor tissues from stage II–IV primary gliomas (n=505) by immunohistochemistry (IHC) for protein levels of both PD-L1 and B7-H4. Gene coexpression analysis assessing clusters based on extent of PD-L1/B7-H4 classifier genes expression were investigated in two transcriptome datasets (The Cancer Genome Atlas and Chinese Glioma Genome Atlas). In addition, levels of immune cell infiltrates were estimated with IHC and RNA-seq data for assessing the tumor immune microenvironment of PD-L1/B7-H4 subgroups. Results High expression of PD-L1 and B7-H4 in gliomas was 23% and 20%, respectively, whereas coexpression of two proteins at high levels was limited to 2% of the cases. Comparable results were seen in RNA-seq datasets where PD-L1 mRNA expression levels negatively correlated with that of B7-H4. Gene coexpression modules clustered within each grade of gliomas demonstrated lack of double-high modules (cluster with high expression of both PD-L1 and B7-H4 classifier genes). B7-H4 mRNA expression levels showed negative correlation with extent of immune cell infiltration and High-B7-H4 module gliomas (high B7-H4 but low PD-L1 classifier genes expression) had less tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). IHC assessment also showed few TILs and TAMs in High-B7-H4 subgroup gliomas. Conclusions The majority of gliomas express PD-L1 or B7-H4, however, coexpression of both at high levels is minimal. The high-B7-H4 patients could be considered as ‘super-cold’ gliomas with significantly deficient in TILs, suggesting that B7-H4 might inhibit T-cell trafficking into the central nervous system. This study demonstrated that PD-L1 and B7-H4 may serve as mutually compensatory immune checkpoint molecules in gliomas for immune targeted or active-specific immunotherapy. The distinct B7-H4 pathways modulating T-cell function and immune evasion in glioma patients deserved to be further explored in the future during immunotherapy.
COVID-19 in rheumatology outpatient clinics: Dutch mirror image to Lombardy, Italy
Authors: Sophie Benoy, Rene Traksel, Peter Verhaegh, Jasper Broen
Journal: Annals of the Rheumatic Diseases (2020)

In response to the article published by Monti et al 1 regarding the clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies, we started to collect similar data from our patients with chronic rheumatic disease as well, to be able to aid in providing preliminary data on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts our patients with immunosuppressive therapies. The first officially reported case in the Netherlands originates from 27 February in the province of North Brabant.2 A few weeks later, after community screening and case identification, it came apparent that the virus had to be present in the community already 2 weeks before the first official case was described. Two and a half million people inhabit North Brabant. In this province, Carnival was celebrated between 21 and 26 February. Carnival is a public celebration in regions of Catholic descent, involving parades and street parties in which at least 200 000 people participate in various cities and villages. It is thought that these public celebrations allowed SARS-CoV-2 to rapidly spread in communities, making North Brabant, together with Limburg (an adjacent province), the regions with the highest number of infections in the Netherlands. Our hospital …
失能老人护理状况调查
Authors: 吕金利, 顾利慧, 陈雪萍, 汤菊萍, 朱晨曦
Journal: BMJ (2012)

2011年8至10月份,以综合性医院、老年专科医院、社区卫生服务机构、养老机构和街道各一家的1036例失能老人为调查对象,用量表进行问卷调查,并对结果进行分析.表明失能老人对护理工作满意度不高。
Preoperative treatment for marginally resectable metastatic melanoma: A single center experience in China.
Authors: Yu Xu, Xuxia Shen, Wei Sun, Yunyi Kong, Yong Chen, Wangjun Yan
Journal: Journal of Clinical Oncology (2020)

e22096 Background: Large randomized trials have proved that targeted therapy (TT) and immunotherapy (IT) can improve RFS for resectable Stage III melanoma. However, there is still a risk around 15%~25% of relapse within 1 year, especially worse for Stage IIID disease. Several neoadjuvant trials have shown a potentiality of long-term relapse-free after a pathologic complete response, especially for immunotherapy. We conducted a prospective study to investigate the impact of preoperative treatment on the anti-tumor efficacy and disease-free survival for Chinese melanoma. Methods: Stage IIID patients with matted nodes were recruited. For BRAF V600E-muted patients, Vemurafenib (V) was given for one months ahead of the surgery. For BRAF-wide-type patients, anti-PD1 antibody, Pembrolizumab(P) or Toripalimab (T) was given one dose per 3 weeks until response or intention-to-progression was observed. Pathologic assessment followed the principles for neoadjuvant therapy established by INMC. Results: Totally seven patients have been recruited. Detail information was listed in Table. Clinical ORR was 71%, however with no pCR observed. One patient in Vemurafenib group occurred brain mets within 1 month after surgery. All four patients in anti-PD1 group were relapse-free so far after median follow-up of 11 months. Conclusions: Preoperative BRAF targeted and anti-PD1 immunotherapy might guarantee a positive impact on anti-tumor response and local disease control for marginally resectable melanoma. However, the pathological criteria for neoadjuvant treatment might not be suitable to evaluate the matted or bulky specimen after preoperative treatment. [Table: see text]
Establishment of adherent endothelial cell layers from human umbilical cord blood CD34+cells during long-term liquid culture using thrombopoietin, FL-3-ligand and granulocyte-colony stimulating factor.
Authors: ES Yoo, JW Seo, Eh Yoo, JY Seoh, Ma Lee, Sa Im, S Lee, SN Lee, Sy Woo, JW Huh, MJ Kim, Jy Ahn, SJ Lee, WS Chung, CM Seong
Journal: Blood (2018)
Machine learning guided adjuvant treatment of head and neck cancer.
Authors: Frederick Howard, Sara Kochanny, Matthew Koshy, Michael T. Spiotto, Alexander T. Pearson
Journal: Journal of Clinical Oncology (2020)

6567 Background: A combined analysis of the EORTC 22931 and RTOG 95-01 trials confirmed that patients (pts) with head and neck squamous cell carcinoma (HNSCC) and positive margins or extracapsular extension (ECE) benefit from adjuvant chemoradiotherapy (CRT), but the best treatment of pts with other risk factors is unclear. We hypothesized that deep learning models could identify the margin/ECE negative pts who benefit from CRT. Methods: We abstracted pts from the NCDB diagnosed from 2004-2016 with resected HNSCC who received radiotherapy (RT). We reserved 20% of pts for validation and used the remaining 80% for feature selection and model training. Features were chosen based on independent significance in a Cox proportional hazards model, and included demographics, tumor stage, site, grade, RT dose, and receipt of chemotherapy. HPV status was included, and imputed when unknown. We generated survival predictions with DeepSurv (DS), random survival forest (RSF), and neural network multitask (NNM) models. We consider CRT to be recommended by a model if predicted survival is longer with CRT than RT. We calculated the median overall survival (mOS) difference and hazard ratio (HR) for receipt of treatment in line with model recommendations. This was repeated with inverse probability of treatment weighting (IPTW) to account for confounding. As a comparator, we used the intermediate risk factors in the EORTC (T3-4 except T3N0 larynx, N2-3, LVI, deep nodes with oral / oropharynx cancer) and RTOG (2 involved nodes) trials as decision rules. Results: 36,831 pts from the NCDB met the inclusion criteria. 92% had T3-4 or node positive disease, and 40% received CRT. RTOG, EORTC, DS, NNM, and RSF models recommend CRT for 32%, 74%, 63%, 61%, and 35% of pts. The concordance index in the validation set was 0.696, 0.692, and 0.699 for DS, NNM, and RSF. Treatment according to model recommendations in the validation cohort was associated with a mOS benefit of 18.4 months (7.6 to 29.3, 95% CI) for DS, 20.5 months (8.8 to 32.2, 95% CI) for NNM, and 5.8 months (-6.6 to 18.3, 95% CI) for RSF. Similar results were seen with IPTW. Conclusions: Machine learning models can predict benefit from CRT in margin/ECE negative pts, and outperform treatment according to EORTC or RTOG inclusion criteria in this cohort. External validation of these models is warranted. [Table: see text]
Clinical value of noninvasive biomarkers reflecting a collagen-rich stroma in metastatic melanoma patients treated with anti-PD1 therapy.
Authors: Christina Jensen, Daan Hurkmans, Stijn L.W. Koolen, Morten A. Karsdal, Ron H.J. Mathijssen, Nicholas Willumsen
Journal: Journal of Clinical Oncology (2020)

3049 Background: Poor response to anti-PD1/PD-L1 remains a clinical challenge in a subgroup of patients with metastatic melanoma. Recent evidence strongly suggests that these poor responses are associated with TGF-β signaling and CD8+ T-cell excluded tumors characterized by a collagen-rich peritumoral stroma that blocks the interaction between T cells and tumor cells. In the pursuit of identifying non-invasive biomarkers associated with a T-cell excluded phenotype and predict resistance/response to immune checkpoint inhibitor therapy, we evaluated the association between blood-based biomarkers measuring type III collagen formation and cross-linking and survival outcomes in metastatic melanoma patients treated with anti-PD1 therapy. Methods: 107 patients with metastatic melanoma who started anti-PD1 monotherapy between May 2016 – March 2019 entered in a prospective real-life study (nivolumab n = 62, pembrolizumab n = 45). Type III collagen formation (PRO-C3) and type III collagen formation and cross-linking (PC3X) were measured with ELISAs in pre-treatment serum. Biomarker levels were associated to Disease Control Rate (according to RECIST v.1.1) by Mann-Whitney test and correlated to survival outcomes by Kaplan-Meier and Cox regression analyses. Results: PRO-C3 was significantly elevated in patients with progressive disease compared to the combined group of patients with complete response, partial response and stable disease (p = 0.046). High PRO-C3 and PC3X ( &gt; 75 th percentile) prior to treatment were significantly associated with poor overall survival (PRO-C3: HR = 2.4, p = 0.008; PC3X: HR = 2.2, p = 0.019) and progression free survival (PRO-C3: HR = 1.91, p = 0.016; PC3X: HR = 1.94, p = 0.013). The median overall survival was 417 and 511 days in biomarker high patients compared to 1269 and 1269 days in biomarker low patients, for PRO-C3 and PC3X, respectively. Conclusions: Biomarkers quantified in a pre-treatment liquid biopsy reflecting excessive collagen formation and cross-linking were associated with poor response and survival outcomes in metastatic melanoma patients treated with anti-PD1 therapy. This supports an association between collagen formation and resistance to anti-PD1 therapy. Furthermore, if validated, these non-invasive collagen biomarkers may have potential for guiding patient stratification for immune checkpoint inhibitor therapy and combination therapies. Clinical trial information: NTR7015 .
More on Neurologic Features in Severe SARS-CoV-2 Infection
Authors: Julie Helms, Stéphane Kremer, Ferhat Meziani
Journal: New England Journal of Medicine (2020)

More on Neurologic Features in Severe SARS-CoV-2 InfectionTo the Editor: In a letter by Helms et al. (published on April 15 at NEJM.org), 1 neurologic features in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are described.We do not concur that there is clearly abnormal leptomeningeal or nodular enhancement in Figures S1 andS3 in the Supplementary Appendix (available with the full text of the letter at NEJM.org).In addition, the perfusion in the frontal and temporal lobes appears to be normal; specifically, these regions do not appear to be hypoperfused.The most common neurologic features in the patients involved in the study by Helms and colleagues were nonfocal: confusion, agitation, dysexecutive syndrome, and diffusely enhanced reflexes.These symptoms and signs do not typically relate to focal brain disease and are not necessarily in accord with the imaging findings.The findings of Helms et al. are concordant with the neurologic findings in patients with Covid-19 in another recent study, 2 and the incidence of these findings may not be disproportionate to the incidence among other critically ill patients.They may not definitively indicate a specific syndrome of brain involvement associated with SARS-CoV-2.
HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: A phase I clinical trial.
Authors: Tong Yang
Journal: Journal of Clinical Oncology (2020)

e16715 Background: Previous studies showed that high intensity focused ultrasound (HIFU) treatment could treat liver tumor and pancreatic cancer, with fewer serious adverse reactions.To evaluate the safety and efficacy of HIFU for patients with colorectal liver metastases(CRLM) that were contraindicated for resection and radiofrequency ablation. Methods: Patients between 20 to 80 years of age with 1-3 liver metastases from colorectal cancer were included. The primary colorectal lesions were thoroughly resected and any case with extra-hepatic metastasis was excluded. Ultrasound guided HIFU system was employed and target region ablation was achieved with repeated sonications from the deep to shallow regions of the tumor section by section. Results: Thirteen patients were enrolled. Pain was the most common adverse events(AEs) (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase(ALT) (n = 5), and skin edema (n = 4). No grade≥3 AEs occurred.The majority of patients (76.9%) had a complete response and the remaining three patients achieved partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but most were isolated only in the liver (8/9). The median follow-up was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and median OS was 25 months. Conclusions: This study indicates that HIFU treatment is safe, has an excellent tumor response and long-termprognosis even when the foci in risky locations, and is probably a considerable option for patients who were unsuitable for other local treatments.
Efficacy and safety of SHR-1210 combined with apatinib in first-line treatment for advanced lung squamous cell carcinoma: A phase II study.
Authors: Jinliang Wang, Zhibo Zhang, Xiang Yan, Junxun Ma, Fan Zhang, Qi Song, Li Zhang, Zhefeng Liu, Bo Yang, Lijie Wang, Haitao Tao, Sujie Zhang, Xiaoyan Li, Jie Hu, Xiaoting Li, Jiaqian Wang, Xiaoyu Zhi, Xiangwei Ge, Shunchang Jiao, Yi Hu
Journal: Journal of Clinical Oncology (2020)

e21587 Background: PD-1 inhibitors plus chemotherapy is a standard of first-line therapy in advanced lung squamous cell carcinoma (LUSC). Previous preclinical and clinical studies suggested that the combination of anti-PD-1 antibody SHR-1210 and VEGFR-2 inhibitor apatinib significantly improved anti-tumor effects. The aim of this study was to evaluate the efficacy and safety of SHR-1210 in combination with apatinib for advanced LUSC patients as a first-line treatment. Methods: In this phase II study, patients diagnosed with stage IIIB or IV advanced LUSC were enrolled. All patients received SHR-1210 (200mg q2w) and apatinib (250mg po qd) until disease progression or unacceptable toxicity. Treatment efficacy was assessed every 3 cycles (6 weeks). The primary endpoint is progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), disease control rate (DCR), and overall survival (OS), which according to RECIST 1.1. Results: At the primary analysis (data cutoff Feb 10, 2020), 26 advanced LUSC patients had enrolled, and 17 patients of which were evaluable. Baseline characteristics were shown that median age was 67 years, male percentage was 92.3% (24/26), and clinical stage IV percentage was for 57.7% (15/26). The median follow-up time was 3.1 months (range 0.4-13.7 months) in all included patients. No complete response (CR) was reported. Partial response (PR) was achieved in 13 (76.5%) and stable disease (SD) in 4 (23.5%). The ORR and DCR in 17 evaluable patients were 76.5% and 100%, respectively. The most common treatment-related adverse events were hypertension (42.3%), rash (38.5%), hand-foot skin reaction (26.9%), and reactive cutaneous capillary endothelial proliferation (RCCEP) (15.4%). Of 26 patients, 5 experienced a grade ≥3 treatment-related adverse events, including one interstitial pneumonia, one hypertension, one thrombocytopenia, one RCCEP, and one aminotransferase elevation. Three patients (3/26) were reported dead, of which one died due to interstitial pneumonia and the others died of tumor progression. Twelve patients (46.2%) ever suspended treatment or adjusted the dosage of apatinib due to interstitial pneumonia, pyelonephritis, rash, thrombocytopenia, or aminotransferase elevation. Conclusions: The combination of SHR-1210 and apatinib for advanced LUSC patients was well tolerated and effective. This treatment may be a promising method for advanced LUSC as a first-line treatment. Fund Project (No: 2017FC-CXYY-3007) &amp; Project (No: 2017MBD-013). Clinical trial information: ChiCTR1800019329.
Predicting value of high-sensitive C-reactive protein on progression of common carotid artery intima-media thickness in newly diagnosed type 2 diabetes
Authors: 刘玉华, 周智广, 宁洁, 黄干, 唐炜立, 谭少珍, 刘志文, 何霞, 熊斌
Journal: BMJ (2006)

目的 探讨多因素强化干预条件下高敏C反应蛋白(hsCRP)水平对新诊2型糖尿病患者颈总动脉内中膜厚度(CCA-IMT)进展的预测作用.方法超声测量318例2型糖尿病患者及112例健康对照者的CCA-IMT,同时检测高敏C反应蛋白水平,并对170例病程1年以内、不伴动脉粥样硬化的2型糖尿病患者进行干预治疗,探讨影响CCA-IMT进展的危险因素.结果高敏C反应蛋白≥1.16 mg/L的2型糖尿病患者CCA-IMT分别高于其他3组高敏C反应蛋白较低者(P＜0.05);2型糖尿病患者CCA-IMT与高敏C反应蛋白呈直线相关(r=0.145,P=0.008);高血压病史、饮酒史、高密度脂蛋白胆固醇、糖化血红蛋白是影响高敏C反应蛋白的独立危险因素;强化干预2年后高敏C反应蛋白水平[0.50 mg/L(0.01～6.63 mg/L)]较基线值[0.60mg/L(0.04～7.84 mg/L)]显著下降(P＜0.01),而CCA-IMT[(0.70±0.21)mm]与基线值[(0.71±0.09)mm]比较差异无统计学意义(P＞0.05);CCA-IMT非进展组患者高敏C反应蛋白降幅[0.07 mg/L(-6.47～7.36 mg/L)]显著高于进展组患者[0.01 mg/L(-7.75～2.93 mg/L),P＜0.01].logistic回归分析显示干预2年后高敏C反应蛋白降幅与CCA-IMT进展独立关联.结论对新诊2型糖尿病患者采取多因素干预,其高敏C反应蛋白水平下降幅度可预测CCA-IMT的进展。
Detection of urothelial carcinoma using plasma cell-free methylated DNA.
Authors: Pier Vitale Nuzzo, Sandor Spisak, Jacob E Berchuck, Sylvan Baca, Keegan Korthauer, Amin Nassar, Sarah Abou Alaiwi, Ziad Bakouny, Ronan Flippot, John A. Steinharter, Catherine Curran, Gwo-Shu Mary Lee, Sushrut Waikar, Mark Pomerantz, Daniel De Carvalho, Guru Sonpavde, Matthew L. Freedman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

5046 Background: Methylation profiling of circulating cell-free DNA (cfDNA) is a promising approach for non-invasive tumor detection due to the presence of tissue-specific epigenetic signatures that are detectable in cfDNA. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMedDIP-seq) is a sensitive, low-input, cost-effective, bisulfite-free approach to profiling cfDNA methylomes, capable of detecting and classifying various tumor types. We tested the feasibility of cfMeDIP-seq to detect urothelial carcinoma (UC) in plasma samples. Methods: We performed cfMeDIP-seq on plasma samples from 43 patients (pts): 18 metastatic UC (UC) pts, 12 pre-cystectomy non-metastatic UC pts, and 13 cancer-free controls. Six (50%) of pre-cystectomy cases were non-muscle invasive UC. cfDNA was immunoprecipitated and enriched using an antibody targeting 5-methylcytosine and PCR-amplified to create a sequence-ready library. The top differentially methylated regions (DMRs) between UC and control samples were used to train a regularized binomial generalized linear model using 80% of the samples as a training set. The 20% of withheld test samples were then assigned a probability of being UC or control. This process was repeated 100 times. Results: The average amount (standard deviation) of cfDNA isolated from 1 ml of UC plasma samples was 29.2 (27.4) ng/µL and 8.02 (3.58) ng/µL in cancer-free controls. We identified 9,826 DMRs in plasma samples at an adjusted p-value of &lt; 0.01, which partitioned UC and control samples. Iterative training and classification of held out samples using the top 300 DMRs resulted in a mean AUROC of 0.987. Conclusions: cfMeDIP-seq is an interesting new approach for non-invasive detection of UC. cfMeDIP-seq demonstrates high sensitivity to detect UC across all stages of UC, including non-muscle invasive disease.
Prevalence of ALK mutations in advanced NSCLC patients in the United States: Analysis with a real world oncology database.
Authors: Timothy Allen, Yan Xiao, Anup Abraham, Stella Redpath, Julia Engstrom-Melnyk, Denise Croix, Baiyu Yang, Roma Shah, Jaya Madala, Eric Bernicker
Journal: Journal of Clinical Oncology (2020)

e21586 Background: ALK mutation rate is widely reported to be 3-7% of advanced non-small cell lung carcinoma (aNSCLC) patients. A cross-sectional study to assess the prevalence of ALK mutations in the real world was performed on the nationwide Flatiron Health electronic record-derived de-identified database. Methods: Patients with aNSCLC (stage IIIB-IV) diagnosed between 1 Jan 2015 – 31 May 2019, age ≥18 at the time of aNSCLC diagnosis, known ALK result and smoking status were included in the analysis. The included patient cohort had 19,895 eligible patients, with a mean age of 68.5 (Standard deviation = 10.0), most of them were ever-smokers (85.5%) and from community centers (92.2%). Results: The overall ALK mutation prevalence was 2.6%. Prevalence of ALK mutation was calculated by age, gender, race, ECOG status and cancer type. Non-smokers had the greatest mutation rate (9.3% non-squamous histology, 6.3% NSCLC histology not otherwise specified [NOS], 3.3% squamous) vs smokers (1.7% non-squamous, 1.4% NSCLC NOS, 0.7% squamous). Differences in ALK status varied by age and race with young patients (18-44 yrs) having a greater mutation rate (16.2%) vs older patients (age 45-64 = 4.5%, age ≥ 65 = 2.2%) and Asian patients having a mutation prevalence of 6.3%. Patients that were positive for other biomarkers (EGFR, ROS1, KRAS or BRAF) had a lower ALK positivity rate (0.5%) while patients reported to be positive for PD-L1 had an ALK mutation rate of 3.0%. Conclusions: While this data overwhelmingly represented testing in the community setting vs academic medical centers, it provides insight into the ALK mutation prevalence across the US. The prevalence of ALK mutations in smokers suggests that a smoking patient (with non-squamous, mixed histology or small biopsy) should not be excluded from testing. This also highlights the need to capture smoking histories as accurate pack-year histories