tbuckley/cabot-search huggingface dataset:
IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).
Authors: Jacek Jassem, Roy S. Herbst, Filippo de Marinis, Jacques Cadranel, Tibor Csőszi, Dolores Isla, Gongyan Chen, Konstantinos N. Syrigos, Diego Cortinovis, Toyoaki Hida, Simonetta Mocci, See Phan, Ida Enquist, Hina Patel, Monette Villalobos, Xiaohui Wen, Yu Deng, Hiroshi Kuriki, David R. Spigel, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2020)

e21623 Background: IMpower110 evaluated atezo mono in PD-L1–selected, chemo-naive patients (pts) with nonsquamous (nsq) or squamous (sq) NSCLC. At the interim analysis, IMpower110 met its primary OS endpoint, with a statistically significant and clinically meaningful improvement for atezo vs chemo in TC3 or IC3 wild-type ( EGFR/ALK-negative) pts. We report on the safety profile of atezo vs chemo in IMpower110. Methods: 572 pts with stage IV nsq or sq NSCLC, PD-L1 expression ≥ 1% on TC or IC and ECOG PS 0-1 were randomized 1:1 to receive atezo (1200 mg IV q3w) or chemo (4 or 6 21-day cycles). In the chemo arm, nsq pts received cisplatin (cis) 75 mg/m 2 or carboplatin (carbo) AUC 6 + pemetrexed (pem) 500 mg/m 2 IV q3w; sq pts received cis 75 mg/m 2 + gemcitabine (gem) 1250 mg/m 2 or carbo AUC 5 + gem 1000 mg/m 2 IV q3w. Safety was assessed in all treated pts (safety evaluable [SE] population [pop]), regardless of PD-L1 expression or EGFR/ALK status. AEs were summarized per MedDRA v22.0 and severity graded per NCI CTCAE v4.0. Immune-mediated AEs (imAEs) were defined per a sponsor-specified list of terms, regardless of whether the events led to systemic glucocorticoid, endocrine therapy, or other immunosuppressants use. Results: At data cutoff (Sep 10, 2018) within the ITT pop, treatment (tx) was ongoing in 90 (atezo: 31.6%) and 25 (chemo: 8.7%) pts, with 13.7 mo of follow-up. Within the SE pop (atezo: n = 286, chemo: n = 263), atezo pts had longer tx exposure (5.3 mo) vs chemo pts (pem, 3.5 mo; gem, 2.6 mo; carbo, 2.3 mo; cis, 2.1 mo). Atezo had a favorable safety profile vs chemo (table); safety data were consistent with data from a pooled atezo mono pop. imAEs occurred in 40.2% (atezo) and 16.7% (chemo) of pts and were Grade (Gr) 3-4 in 6.6% and 1.5%, respectively. Conclusions: Atezo was better tolerated than chemo and imAEs were generally low grade. Overall, the safety experience with atezo mono in IMpower110 was consistent with its known safety profile; no new safety signals were identified. Clinical trial information: NCT02409342. [Table: see text]
H&amp;E image-based consensus molecular subtype classification of colorectal cancer using weak labeling.
Authors: Andrew J. Kruger, Lingdao Sha, Madhavi Kannan, Rohan P. Joshi, Benjamin D. Leibowitz, Renyu Zhang, Aly A. Khan, Martin Stumpe
Journal: Journal of Clinical Oncology (2020)

e16097 Background: Using gene-expression, consensus molecular subtypes (CMS) divide colorectal cancers (CRC) into four categories with prognostic and therapy-predictive clinical utilities. These subtypes also manifest as different morphological phenotypes in whole-slide images (WSIs). Here, we implemented and trained a novel deep multiple instance learning (MIL) framework that requires only a single label per WSI to identify morphological biomarkers and accelerate CMS classification. Methods: Deep learning models can be trained by MIL frameworks to classify tissue in localized tiles from large ( &gt; 1 Gb) WSIs using only weakly supervised, slide-level classification labels. Here we demonstrate a novel framework that advances on instance-based MIL by using a multi-phase approach to training deep learning models. The framework allows us to train on WSIs that contain multiple CMS classes while further identifying previously undiscovered tissue features that have low or no correlation with any subtype. Identification of these uncorrelated features results in improved insights into the specific tissue features that are most associated with the four CMS classes and a more accurate classification of CMS status. Results: We trained and validated (n = 735 WSIs and 184 withheld WSIs, respectively) a ResNet34 convolutional neural network to classify 224x224 pixel tiles distributed across tumor, lymphocyte, and stroma tissue regions. The slide-level CMS classification probability was calculated by an aggregation of the tiles correlated with each one of the four subtypes. The receiver operating characteristic curves had the following one-vs-all AUCs: CMS1 = 0.854, CMS2 = 0.921, CMS3 = 0.850, and CMS4 = 0.866, resulting in an average AUC of 0.873. Initial tests to generalize to other data sets, such as TCGA, are promising and constitute one of the future directions of this work. Conclusions: The MIL framework robustly identified tissue features correlated with CMS groups, allowing for a more efficient classification of CRC samples. We also demonstrated that the morphological features indicative of different molecular subtypes can be identified from the deep neural network.
An investigation on prevention and treatment of chronic obstructive pulmonary disease at two community health service centers in urban and suburban Shanghai
Authors: Xun Xu, Fan Li, Xue-min Zhang, Wang-hui Zhu, Huan-ying Fu, Chao-ying Shen, Yuan-ying Lu, Qi-jun Zhuang, Jian-feng Yin, Su-hua Li, Wei-wen Yin, Mei-hua Zhou, Xiao-li Chen, Ying-yun Cai
Journal: BMJ (2009)

Objective The purpose of this study was to investigate and analyze current status of prevention and treatment for chronic obstructive pulmonary disease (COPD) at two community health service centers in urban and suburban Shanghai.Methods Among 711 patients with chronic cough and shortness of breath aged more than 40 years who visited Xiaokunshan and Xinbang community health service centers in Songjiang district of Shanghai, 132 were diagnosed as COPD and a face-to-face interview was conducted for all of them with questionnaires to understand current status of community prevention and treatment of COPD.Results Among 132 COPD patients, six (4.5%) were classified as stage Ⅰ, 29 (22.1%) as stage Ⅱ, 58 (43.9%) as stage Ⅲ and 39 (29.5%) as stage Ⅳ, respectively, according to their pulmonary function.Sixty-eight (51.5%) of them never smoked, 40 (30.3%) were past smokers but now quitters and 24 (18.2%) were current smokers, respectively.All the 126 smoking patients of COPD, including five at stage Ⅱ, 12 at stage Ⅲ and seven at stage Ⅲ, never underwent pulmonary function tests, and only 46 (36.5%) of those at stages Ⅱ, Ⅲ and Ⅳ visited out-patient clinics over the past year and 35 (27.8%) were hospitalized.Sixteen of them (12.1%) were once orally administered with theophyllines, 24 (18.2%) with β2receptor agonists, nine with (6.8%) inhaled bronchodilators, only three (2.3%) with inhaled corticosteroid hormones, respectively, over the past year.Twenty-six (19.7%) patients with COPD took illicit drugs of unknown ingredients and without production batches licensed by the State Food and Drug Administration (SFDA).Among 97 COPD patients at stages Ⅲ and Ⅳ, only one received long-term home oxygen therapy.Conclusion Management of COPD patients at community level was inadequate and should be standardized.

Key words: 
Pulmonary disease;  chronic obstructive;  Community health centers;  Questionnaire
Abstract 11426: Biomarkers of Inflammation and Fibrosis in the Young Adults With History of Kawasaki Disease
Authors: Shinsuke Hoshino, Chisato Shimizu, Samantha C Roberts, Lori B Daniels, Adriana H Tremoulet, John B Gordon, Jane C Burns
Journal: Circulation (2019)

Introduction: Molecular profiling using shotgun proteomics, transcriptomics, and glycomics methods revealed active inflammation in adult patients with a history of Kawasaki disease (KD) and giant c...
Impact of diabetes and stroke on long-term outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Mingzhong Zhao, Mingyuan Du, Tiangang Zhu, Juan Yu, Chao Zhang, Haobing Hu, Huimin Li, Yong Cheng, Dayi Hu
Journal: BMJ (2020)

Objective
To investigate the impact of diabetes mellitus (DM) and stroke on long-term outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).


Methods
Total 411 consecutive ACS patients undergoing PCI at the Ninth People′s Hospital of Zhengzhou between December 2014 and June 2018 were recruited, including 319 males and 92 females with a mean age of (64.7±10.1) years. These patients were divided into 4 groups according to the presence or absence of history of diabetes or stroke: non-DM non-stroke group (n=192) , DM group (n=140), stroke group (n=41), and DM+stroke group (n=38). The data of baseline demographic characteristics, clinical feature, coronary angiographic findings, and cardiovascular adverse events during long-term follow-up were obtained. Kaplan-Meier curves were used to investigate the long-term clinical outcomes among groups.


Results
The mean interval of follow-up was (24.1±13.8) months. Patients with DM+stroke had the highest rates of non-fetal myocardial infarction (χ2=24.932) , non-fetal stroke (χ2=9.434) , hospitalization due to heart failure/angina (χ2=69.290) , revascularization (χ2=22.918) , cardiovascular death(χ2=13.473)and all-cause death(χ2=17.724)as well as hard endpoint events (the sum of non-fetal myocardial infarction, non-fetal stroke, and all-cause death) (χ2=30.268)and combined major adverse cardiovascular events (MACE) (the sum of hard endpoint events, hospitalization due to heart failure/angina, and revascularization) (χ2=119.556)among 4 groups(all P 0.05) . Meanwhile, patients with DM+stroke presented significantly lower cumulated ratio free from combined MACE than patients with non-DM non-stroke (HR=5.423, 95%CI:2.941-10.036, P<0.01), and the cumulated ratio free from combined MACE also decreased significantly in DM+stroke group as compared to DM group or stroke group respectively (HR=1.859,95%CI: 1.167-2.962; HR=1.991,95%CI: 1.178-3.364; all P<0.01) .


Conclusions
ACS patients with combined history of DM and stroke have a worse long-term outcomes after PCI than those with DM alone or stroke alone or without DM or stroke. DM and stroke seemed to have an additive effect on decrease in the cumulative ratio free from combined MACE in ACS patients following PCI.


Key words: 
Diabetes mellitus; Stroke; Acute coronary syndrome; Major adverse cardiovascular events; Percutaneous coronary intervention
Electronic patient-reported outcomes (ePROs) and machine learning (ML) in predicting the presence and onset of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapies.
Authors: Sanna Iivanainen, Jussi Ekström, Vesa V Kataja, Henri Virtanen, Jussi Koivunen
Journal: Journal of Clinical Oncology (2020)

e14058 Background: ICIs have introduced novel irAEs, arising from various organ systems without strong timely dependency on initiation and discontinuation of the therapy. Early detection of the irAEs could result in improved safety profile of the treatment and better quality of life for patients. Symptom data collected by ePROs could be used as an input for ML based prediction models for early detection of irAEs. Methods: The utilized dataset consisted of two data sources. The first dataset consisted of 16 540 reported symptoms from 33 ICI-treated cancer patients, including 18 monitored symptoms collected using Kaiku Health digital platform. The second dataset included prospectively collected irAE data, including initiation and end dates, CTCAE class, and severity of 26 irAEs (the longest irAE lasted 799 days, and the shortest two days while median duration was 61 days). Two ML models were built using extreme gradient boosting, a well-known classification algorithm. Using the ePRO data, the first model was trained to detect the presence and the second model to detect the onset (0-21 days prior to diagnosis) of irAEs. The dataset was split into training (70 % of the data) and test sets (30 % of the data) by random allocation. The test set was left out from the model training and tuning, and was used only to evaluate the model performance. Results: The model trained to predict the presence of irAEs had an excellent performance with the test dataset. The prediction of the irAE onset was more difficult, but the model performance was still at a very good level. The performance metrics for the ML models are presented in Table. Conclusions: Current study suggests that ML based prediction models, using ePRO data as input for the models, can predict the presence and onset of irAEs with high accuracy. Thus, it indicates that digital symptom monitoring combined with ML could enable the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset from prospective clinical trials. Clinical trial information: NCT03928938. [Table: see text]
The dynamic change of cancer genome and T-cell receptor repertoire of an early gastric cancer cohort.
Authors: Zhuoran Li, Jing Bai, Xi Wu, Weixun Zhou, Yaping Xu, Ling Yang, Aiming Yang
Journal: Journal of Clinical Oncology (2020)

e16553 Background: The dynamics of the cancer genome and T-cell receptor (TCR) repertoire are largely unclear during the development of gastric cancer, especially in the early stage. In this study, we studied the characteristics of genome and tumor microenvironment changes chronologically in 15 early gastric cancer (EGC) patients and illustrated their influence on carcinogenesis. Methods: 75 gastric tissues including precancerous lesions, cancer lesions and paired reference gastric samples, and 29 peripheral blood samples were obtained chronologically from 15 patients. All the lesions were categorized into 3 groups according to its pathology type (group1: inflammation or intestinal metaplasia, group 2: low-grade dysplasia (LGD), group 3: EGC). Deep sequencing of whole-exome and CDR3 chain of TCR of each sample was performed. Tumor mutation burden (TMB), TCR repertoire diversity and clonality were evaluated based on the sequencing data. Results: Heterogeneity existed in cancer genome and TCR repertoire among different patients. During carcinogenesis, TMB increased at first and then decreased, reaching its peak at LGD, which was different from what we have known from other advanced cancer. A detailed analysis showed that only part of the driver gene mutations maintained in this process. Compared with T cells infiltrated in reference samples, tumor-infiltrating T cells shared more clones with peripheral blood T cells. Diversity and clonality of TCR repertoire didn’t show significant change with the development of cancer (Shannon index: group 1 = 6.32, group 2 = 6.06, group 3 = 6.09, p = 0.836; Clonality: group 1 = 0.19, group 2 = 0.19, group 3 = 0.17, p = 0.374). Some CDR3 clones appeared in early-stage and maintained during the carcinogenesis process. Conclusions: Our research is the first to analyze the cancer genome and TCR repertoire changes from both the spatial and temporal perspectives during the development of early gastric cancer. Somatic mutations appeared in the very early stage of gastric cancer and may induce the immune microenvironment changes in gastric mucosa.
Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence.
Authors: Hope S. Rugo, Louis W. C. Chow, Javier Cortes, Peter A. Fasching, Pei Hsu, Chiun-Sheng Huang, Sung-Bae Kim, Yen-Shen Lu, Michelle E. Melisko, Rita Nanda, Priyanka Sharma, Richard B. Schwab, Binghe Xu
Journal: Journal of Clinical Oncology (2020)

TPS599 Background: Adagloxad simolenin (AS) is a therapeutic vaccine comprising the tumor-associated antigen Globo H linked to the carrier protein keyhole limpet hemocyanin (KLH). The KLH provides antigenic immune recognition and T-cell responses. AS is co-administered with a saponin-based adjuvant OBI-821 to induce a humoral response. A phase 2 trial showed that AS/OBI-821 exhibited a trend for superior progression-free survival vs placebo in patients whose breast cancers have higher Globo H expression. Methods: Patients with TNBC (ER/PR &lt; 5%, and HER2-negative) with nonmetastatic disease and either 1) residual invasive disease of ≥1 cm in the breast or ≥1 positive axillary node following neoadjuvant chemotherapy or 2) ≥4 axillary lymph nodes with invasive carcinoma treated with adjuvant chemotherapy are included. Patients are prescreened for Globo H expression using a validated IHC assay (H-score of ≥15). Patients will receive either AS (30 μg) with OBI-821 (100 μg) or volume-matched placebo (1:1), administered as SC injections. Up to 21 SC injections of study treatment (or placebo), will be administered over 100 weeks, given on the following schedule: weekly for 4 doses; every 2 weeks for 4 doses; every 4 weeks for 4 doses; and then every 8 weeks for 9 doses. Patients may terminate treatment due to disease recurrence or unacceptable toxicity, withdrawal of consent, protocol violation, loss to follow-up or death. The primary objective is to determine the effect of AS/OBI-821 treatment on invasive disease-free survival in patients with TNBC at high risk for recurrence. Secondary objectives are to determine the impact of AS/OBI-821 treatment on overall survival, quality of life (QoL), breast cancer-free interval, distant disease-free survival, safety, and tolerability. Imaging and clinical examination will be performed regularly for 5 years. QoL will be assessed using the EORTC Core Quality of Life Questionnaire (QLQ)-C30 plus the EORTC Breast Cancer-specific QLQ-BR23 questionnaire and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire. Adverse events will be graded/recorded as per National Cancer Institute CTCAE v5.0. An estimated 668 subjects will be enrolled, treated for up to 2 years and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NTC03562637 .
Effects of intensive insulin therapy on function of pancreatic islet (C-Peptide releasing function) in diabetics with secondary sulfonylureas failure
Authors: 职冬悦, 邵晋康
Journal: BMJ (2004)

目的 了解磺脲类降糖药继发失效(SF)者的胰岛功能及胰岛素强化治疗后的变化.方法临床设计分为3组:SF组50例,非继发失效组(NSF)49例及健康对照组(C)35例.胰岛素强化治疗使糖化血红蛋白(HbA1c)水平 0.05),但与C组比较峰值仍低且明显后移.结论磺脲类降糖药继发失效者胰岛功能损害明显重于非失效患者,胰岛素强化治疗明显有助于胰岛功能的恢复。
大力发展我国临终关怀事业的必要性和可能性
Authors: 张明生, 周云峰
Journal: BMJ (2005)

临终关怀是人类死亡文明的重大成果,从某种意义上来说,它是人类文明进步的一个标志.一个国家或地区临终关怀事业发展的好坏,从一个侧面体现了这个国家或地区社会文明发展的程度.随着人类文明的发展,伦理道德观念的转变,临终关怀已逐步成为一种社会需要.我国的临终关怀事业还处于刚刚起步的阶段,与国外还有很大差距,亟需大力发展.笔者就发展我国临终关怀事业的客观必要性和现实可能性谈点认识。
培养全科医生实战能力最重要
Authors: 郑永腾
Journal: BMJ (2010)

尊敬的编辑老师:您好! 感谢采用了我的文章 . 很久以来,作为一个凭借实践锻炼而成就的全科医生,我深刻而具体地感受到实用二字对全科医生的重要性.在几年前,我由单位委派到某医科大学去学习全科医学,那时我已经通过国家的考试,获得了全科医学专业中级证书。
心血管疾病院前急救109例
Authors: 李锁兰
Journal: BMJ (2004)

现代医学的发展和社区医疗的普及,使基层门诊处理急诊、抢救的机会越来越多,如何提高抢救的成功率,减少院前抢救死亡事件的发生,是院前急救医学研究的重要课题.我部自1996年1月～2004年1月共出诊抢救心血管病例109人次,现就其临床相关特点作如下分析。
呼吸困难-水肿
Authors: 陈江天, 张方芳
Journal: BMJ (2009)

患者,女性,90岁,主因活动后呼吸困难1个月,全身水肿10 d于2008年4月12日收入院.患者1个月前受凉后咳嗽,发热,体温37.8℃,无咳痰、咽痛及流涕,伴活动后呼吸困难,休息约半小时可自行缓解.曾于社区医院查血常规:白细胞12.8×109/L,分类中性粒细胞0.84,淋巴细胞0.19,嗜酸性粒细胞0.007,血红蛋白115 g/L.胸部X线片提示左侧肺炎.给予头孢呋辛钠静脉滴注7 d后呼吸困难好转,无发热.复查血白细胞7.9×109/L,分类中性粒细胞0.74,淋巴细胞0.25,嗜酸性粒细胞0.01.随后改为口服诺氟沙星.1 d后开始出现双下肢水肿,凹陷性,逐渐加重,10 d来水肿已扩展到胸前区,喜右侧卧位,伴水肿部位瘙痒,为进一步诊治收入院。
Phase I study of the antibody-drug conjugate ABBV-321 in patients with non-small cell lung cancer and squamous head and neck cancer with overexpression of the epidermal growth factor receptor.
Authors: Benedito A. Carneiro, Christine M. Bestvina, Einat Shacham Shmueli, Hui Kong Gan, Joseph Thaddeus Beck, Randy Robinson, JuDee S. Fischer, Amber Wong, Peter J Ansell, Janet Yikai Jin, Louie Naumovski, Kyriakos P. Papadopoulos
Journal: Journal of Clinical Oncology (2020)

TPS3649 Background: ABBV-321 (serclutamab talirine) is an epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate that consists of a humanized immunoglobulin G1 anti-EGFR monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer via a maleimidocaproyl-valine-alanine linker. Once bound, ABBV-321 is internalized, the maleimidocaproyl-valine-alanine linker undergoes proteolytic cleavage, and the cytotoxic PBD is released, causing DNA cross-links and cell death. Preclinical studies have shown cytotoxicity in numerous human xenograft and patient (pt)-derived tumor models. This first-in-human trial is assessing the safety, pharmacokinetic (PK), and preliminary antitumor activity of ABBV-321 in pts with advanced solid tumor types likely to exhibit elevated levels of EGFR. Methods: This is a 2-part, multicenter phase 1 study (NCT03234712) of ABBV-321 monotherapy in pts (≥18 years; Eastern Cooperative Oncology Group performance status 0–1) with advanced solid tumors associated with overexpression of EGFR. EGFR overexpression will be determined by centralized testing using an RNA-based assay. Primary objectives of the completed part 1 (dose escalation) were to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of ABBV-321 and assess the PK and toxicity and safety profile; part 2 (dose expansion) will evaluate safety and PK profile at the RP2D in specific cohorts (NSCLC and HNSCC). Secondary objectives include assessment of preliminary antitumor activity. Pts will receive escalating doses of ABBV-321 until the MTD/RP2D is determined. Dose-limiting toxicities will be assessed during the first cycle of dosing. Adverse events (AEs) will be evaluated per National Cancer Institute Common Terminology Criteria for AEs (version 4.03). Blood samples for PK analysis (ABBV-321, total antibody, unconjugated PBD) will be collected at designated time points throughout the study. The multinational trial is active, with the first pt screened on 1 Feb 2018. The dose-escalation phase has been completed; screening and enrollment for the expansion phase of the study in NSCLC and HNSCC is underway. Clinical trial information: NCT03234712 .
心血管介入术后动脉鞘管拔管并发症分析
Authors: 李丕宝, 孙守生, 曹万才, 徐庆国, 王磌, 张迅英
Journal: BMJ (2005)

随着心血管介入诊疗术的广泛开展,有关术后动脉鞘管拔管(简称拔管)的并发症应引起临床重视.现对我院自 2002年 10月至2003年 12月完成的168例经动脉途径心血管介入诊疗术后拔管并发症进行回顾性分析,报告如下。