tbuckley/cabot-search huggingface dataset:
The impact of affordable care act on the treatment disparities for stage-IV colorectal cancer: A contemporary analysis.
Authors: Thejus Thayyil Jayakrishnan, Veli Bakalov, Zena Chahine, Gene Grant Finley, Dulabh K. Monga, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

e19082 Background: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act on the interaction of socioeconomic factors with treatment enrollement and survival in patients with metastatic colorectal cancers. Methods: We queried the National Cancer Database (NCDB) for patients with Stage-IV colon (C-Ca) and rectal cancers (R-Ca) diagnosed from 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis. Enrollment rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy (denominator) and used to calculate incident-rate ratios that was further analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, &lt; 1 indicating lower enrollment rate). Multivariate Cox-proportional hazard model was performed for survival analysis and reported as calculate Hazard Ratios (HR). Results: We identified 59,211 C-Ca and 4,818 R-Ca for the analysis. Median ages were 64 years vs. 60 years and included 52% vs. 60% males respectively. For C-Ca enrollment to primary therapies were significantly associated (p-value &lt; 0.05) with gender, race, insurance status, educational status and treatment facility. HR &lt; 1 was associated with high-income vs. low-income group- 0.90(0.87-0.94),p-value &lt; 0.005. The HR for non-Hispanic Blacks (NHB) vs. Whites (NHW) improved from 1.1(1.03-1.11),p-value &lt; 0.005 to no-significant difference post-ACA. For R-Ca, the enrollment rates were favorable for NHB vs. NHW and ER improved from 1.15(1.0-1.32),p-value = 0.054) to 1.29(1.06-1.58),p-value = 0.013 post-ACA. Despite this, the HR for mortality were unfavorable - 1.19(1.06-1.33),p-value = 0.003 that persisted through the post-ACA period. The HR was favorable for the insured group in both cancer groups (0.84 for R-Ca,0.86 for C-Ca). Conclusions: Socioeconomic factors influence outcomes for this vulnerable group of patients in terms of enrollment to therapies and survival. The Affordable Care Act appears to have had a positive impact overall but more needs to be done including broadening insurance coverage.
The promise and challenge of cancer microbiome research
Authors: Sumeed Syed Manzoor, Annemiek Doedens, Michael B. Burns
Journal: Genome biology (2020)

Abstract Many microbial agents have been implicated as contributors to cancer genesis and development, and the search to identify and characterize new cancer-related organisms is ongoing. Modern developments in methodologies, especially culture-independent approaches, have accelerated and driven this research. Recent work has shed light on the multifaceted role that the community of organisms in and on the human body plays in cancer onset, development, detection, treatment, and outcome. Much remains to be discovered, however, as methodological variation and functional testing of statistical correlations need to be addressed for the field to advance.
Molecular testing patterns and implications for treatment at a cancer center.
Authors: Clarissa Lam, Adrianne Rose Mallen, Christine Marie Walko, Jing-Yi Chern
Journal: Journal of Clinical Oncology (2020)

e13576 Background: Genetic testing has revolutionized the care of ovarian cancer, providing a potential for targeted therapies and cancer prevention through cascade testing. Previous historical control for genetic testing rate of 28.5% at our institution, this initiated a multilevel intervention to improve guideline concordant care. The main objective of this study is a descriptive analysis of genetic testing patterns with the implementation of a genetics tumor board (GTB) at an NCI comprehensive cancer center (CCC). Methods: All gynecologic oncology cancer patients who underwent somatic testing from 3/2019 to 1/2020 were included in gynecologic oncology GTB. A descriptive analysis was performed on the ovarian cancer patients. Information regarding patient demographics, cancer characteristics, treatment, and follow-up were obtained from the medical records. Results: There were a total of 81 patients included in GTB during this time period. Fifty-four of 81 (66.7%) received care at our CCC and 27 of 81 (33.3%) were seen as a second opinion case. The patients included in GTB were comprised of recurrent ovarian cancer cases and newly diagnosed ovarian cancer cases. Of the patients included in genetics tumor board, 58 of 81 (71.6%) of patients received both germline and somatic testing. Genetics referrals were placed for 16 of 23 (69%) of the patients who received somatic testing without subsequent germline testing. Twelve of 81 (14.8%) GTB patients were identified for clinical trials during this time period. Conclusions: Genetic testing has become a cornerstone to ovarian cancer care. Implementation of a genetics tumor board at our institution has increased rates of germline testing compared to historical controls. With genetic tumor board being made up of a third of patients seeking a second opinion, we are able to provide comprehensive care to such patients in the form of genetic counseling referrals and clinical trial opportunities. Genetics tumor board also appears to highlight the cohort of patients with the most aggressive cancers: high-grade, advanced stage, and high rates of recurrence. This can potentially improve care by providing an arena for a multidisciplinary discussion of our most complex patients. Ongoing studies with the implementation of our cancer pathways may help determine which modifiable factors can be targeted to help increase adherence to genetic testing recommendations as we continue to strive for guideline-based care.
糖皮质激素在儿童呼吸系统疾病中的应用
Authors: 代继宏, 孙宇星
Journal: BMJ (2012)

糖皮质激素是一类临床使用非常广泛的药物,其主要作用有抗炎、抗毒、抗休克等.如何在儿童呼吸系统疾病中正确使用此类药物非常重要,本文围绕儿童常见呼吸系统疾病,如:支气管哮喘、咳嗽变异性哮喘,毛细支气管炎、急性感染性喉炎等疾病,简要阐述糖皮质激素的用法、适应证等,合理使用、避免不良反应发生,更好地为广大患儿服务。
Effect of uncommon and insensitive mutation on EGFR-TKI in treatment of non-small cell lung cancer.
Authors: Hui Zhang, Da Jiang, Suju Wei, Yanzhi Cui, Ying Li, Caijuan Tian, Qian Dong, Zanmei Xu
Journal: Journal of Clinical Oncology (2020)

e21652 Background: EGFR-TKI application is directed by the situation of mutations of epidermal growth factor receptor, in addition, the mutations of ALK, ROS-1,C-met, BRAF, Her-2, RET,NTRK1, PI3K, MEKI have potential effects on guiding treatment. This study aimed to investigate the uncommon and insensitive mutations and their effect on prognosis in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Methods: 21 NSCLC patients treated with EGFR-TKIs were enrolled, 9 with Gefitinib, 5 with Osimertinib and 7 with Icotinib. All patients were detected with targeted NGS 1000 gene panel. Afterwards, the EGFR sensitive mutation, uncommon mutation and mutations accompanied EGFR T790M were analyzed. Furthermore, the correlations of gene mutation with metastasis, OS and PFS were analyzed. SPSS 21.0 was used for statistical analysis, t test for continuous variables and χ 2 test for classified variables. Results: In all the patients, EGFR p.[T790M] and p.[L858R] mutations were detected in 4.76% and 23.81% of the patients, respectively. In the 5 patients treated with Osimertinib, one had EGFR p.[T790M] mutation and curative effects was stable disease (SD). The mutations accompanied EGFR T790M included SMARCA4 p.[K1390Q] (2.23%), DNMT3A p.[F755S] (2.17%), MTOR p.[Y1450*] (2.15%), TPMT p.[L182R] (1.84%), etc. For the other four patients treated with Osimertinib, two of them were partial response (PR) and two were SD, accompanied with mutations such as EGFR p.[L858R] (55.00%), ARID1A p.[P16del] (2.83%), TP53 p.[R248W] (21.73%) and AR p.[Q60L] (4.24%). In addition, among all the mutations, 18 uncommon mutations were detected, in which ATM (23.26%), AR (23.26%) and MTOR (37.21%) were markedly associated with OS. Besides, the mutation frequency of 67 genes, such as ABCG2, AURKA, EPHA3 and ATR were correlated with OS. The mutation frequency of FGFR1 was significantly different between the patients with and without metastasis. The mutations of 22 genes, for instance ABCG2 p.[P21L], FAT1 p.[L398F], GNAS p.[F226V] and KMT2C p.[N2842Ilefs], were correlated with PFS during the treatment. Conclusions: EGFR-TKI has similar curative effects in EGFR p.[T790M] negative patients. Gene mutations, including uncommon mutations and EGFR insensitive mutations, can significantly affect the prognosis in NSCLC patients treated with EGFR-TKIs.
ATM mutation carriers and family history of pancreatic cancer.
Authors: Jeannie Klavanian, Dana Zakalik, Anish S Konde, Tara Rangarajan
Journal: Journal of Clinical Oncology (2020)

1529 Background: Multigene panel testing (MGT) is commonly utilized in patients with a personal or family history of cancer. One of the more common gene mutations identified is in the ATM gene, associated with a moderately increased risk of breast and other cancers. There are reports of an association with pancreatic cancer, however the exact risks are unclear. The aim of this study is to describe the family history of pancreatic cancer in a cohort of ATM mutation carriers, and to evaluate possible genotype/phenotype correlation. Methods: Patients who underwent MGT, between ‘13 and ‘19, and tested positive for a pathogenic/likely pathogenic ATM mutation were included in this study. Family history, with a focus on pancreatic cancer, and genetic testing results were analyzed. Results: A total of 114 patients were identified to carry an ATM mutation. Twenty-two (19.3%) individuals had a family history of pancreatic cancer in a close relative, and of those, 13 (11.4%) had an affected first degree relative, and 11 (9.6%) had an affected second degree relative. Among the families with pancreatic cancer, 20 close relatives had a personal history of pancreatic cancer, with the youngest diagnosed at age 40, the oldest diagnosed at age 91, and a mean age of diagnosis of 66.5 years. Thirteen unique variants were identified: 4 splice site, 3 missense, 3 frameshift, 1 nonsense, and 1 silent. Two families had the known high-penetrance ATM mutation, c.7271T &gt; C (p.V2424G). Conclusions: This study describes the association of pancreatic cancer in individuals found to carry pathogenic ATM mutations. A significant proportion (19.3%) of patients had a family history of pancreatic cancer in a close relative, diagnosed as young as age 40. The mean age of diagnosis was slightly younger than the average age in the general population (age 70). As pancreatic cancer screening continues to improve, this information will be an important component to help guide cancer risk assessment and future screening recommendations for ATM mutation carriers. Additional larger studies are needed to further characterize pancreatic cancer risks in patients with ATM gene mutations.
从一位腰痛患者的诊治看全科医生的临床思维
Authors: 周仲华
Journal: BMJ (2005)

[前言] 2002年5月,沈阳市家庭医生国际门诊成立了,在这个门诊工作的医生都是来自美国的家庭医生.Dr.Peter Burgos是门诊的常驻医生,他说一口流利的汉语,为人真诚,充满爱心.他和他的妻子及他们的4个孩子在沈阳生活已经快7年了.除了Peter医生之外,还有Dr.Boyd, Dr.Neal, Dr.Foster等先后在诊所工作过半年到1年不等的时间.来诊所工作的还有一些短期到中国工作的美国医生志愿者.这些美国家庭医生到中国来工作最主要的目的是通过帮助培养中国的家庭医生而帮助更多的中国人。
The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 and affects the biological functions of esophageal cancer cells.
Authors: Yichen Zhou, Honglei Zhu, Xuezhou Pang, Yang Shen, Yu He, Daiyuan Ma
Journal: Journal of Clinical Oncology (2020)

e16531 Background: The mechanism by which radiotherapy regulates PD-L1 expression and affects the biological behavior of esophageal cancer cells is not clear.The IL-6 /STAT3 signaling pathway may be involved. Methods: After irradiation of different doses to the esophageal cancer cell lines (Eca109, KYSE150, and TE1), RT-PCR and Western blotting were used to detect PD-L1, STAT3 and P-STAT3, ELISA was performed to examine the effects on IL-6, CCK-8 assays were used to test the effects on the proliferation. After the optimal dose radiation, Transwell assays were used to detect the invasion and proliferation of cell clones, and cell cycle changes were detected by flow cytometry. Results: The mRNA and the protein expression of PD-L1 in the cancer cell lines was significantly higher than in the normal esophageal cell line HET-1A(P &lt; 0.01). The PD-L1 mRNA levels first increased and then decreased, which peaked 12 hours after 3,6,9,12Gy irradiation and was significantly higher than in nonirradiated cells (P &lt; 0.05). PD-L1 protein expression first increased and then decreased, which peaked 48 hours after 6 Gy irradiation (P &lt; 0.05). P-STAT3 protein expression first increased and then decreased after 6Gy irradiation (P &lt; 0.05), that the expression in Eca109 peaked 48 hours but in KYSE150 and TE1 peaked 24 hours (P &lt; 0.05). IL-6 protein expression peaked 12 hours and decreased gradually after irradiation (P &lt; 0.05). The proliferation levels of the the cancer cell lines decreased after irradiation, and the inhibitory force increased with the increase in dose and time after radiotherapy (P &lt; 0.05). The clone formation ability of the cancer cell lines was inhibited to varying degrees 14 days after irradiation with 6 Gy(P &lt; 0.05). After 48 hours irradiation with 6 Gy, and the invasion ability of the cancer cell lines was lower than that of the nonirradiated cell lines (P &lt; 0.05), and the proportion of cells in G2/M phase was higher in exposed cells than in nonexposed cells (P &lt; 0.05), while the proportion of cells in S phase did not change significantly. Conclusions: PD-L1, IL-6 and STAT3 protein expression in the esophageal cancer cell lines first increased and then decreased consistency after irradiation, radiotherapy could regulate PD-L1 expression through the IL-6/STAT3 signaling pathway and affect the biological functions of esophageal cancer.
以腹痛腹泻为首发症状的系统性红斑狼疮一例
Authors: 张虹, 梅坚, 李芹, 毕丹艳, 和芳
Journal: BMJ (2005)

患者女,17岁,学生.因腹痛、腹胀、腹泻4个月余,加重伴恶心、呕吐5 d,于2004年11月17日住我院消化科.患者于2004年7月无诱因出现腹胀、排便困难、脐周持续性绞痛,外院予大黄治疗后出现腹泻6～7次/d,为黄色稀水或黏液便,伴恶心、呕吐,呕吐物为胃内容物及胆汁样物,症状时好时坏.8月份住外院拟诊为系统性红斑狼疮(SLE),给予泼尼松20 mg/d,治疗约10 d后大便成形,腹痛无减轻,又诊为结核性腹膜炎,停用泼尼松,予抗结核治疗(异烟肼0.3 g/d,利福平0.45 g/d,乙胺丁醇0.75 g/d),腹痛、腹胀缓解于10月份出院.此后大便均成形,但仍时有腹痛、腹胀.入院前5 d症状加重,再次出现恶心、呕吐、腹泻.既往史:无特殊.无药物及食物过敏史.查体:体温36.9℃,脉搏112 次/min,呼吸21 次/min,血压 86/65 mm Hg(1 mm Hg= 0.133 kPa),急性痛苦病容,皮肤巩膜无黄染,浅表淋巴结无肿大,心肺(-),腹软,上腹正中及脐周压痛,无肌紧张及反跳痛,肝、脾未触及,移动性浊音(-),肠鸣音6～8 次/min,下肢不肿。
耳鼻咽喉头颈外科在全科医师教学培训中的实践和体会
Authors: 王振霖, 张秋航, 孔锋, 张名霞, 杨治宇, 齐岩
Journal: BMJ (2011)

全科医学教育是未来几十年内我国医学教育改革的重要方向,高等医学院校是全科医师临床能力教学和培训的主渠道[1].目前,针对全科医师教育的研究多从宏观角度出发,倾向于对整体布局、教学理论和基础知识培训方面的探索,缺乏参与临床教学的具体专科在临床带教中的经验总结.我们根据参与北京市全科专科医师教学培训的一些经验,针对发现和存在的问题进行了分析和初步探讨。
The validity of VALID act: Cost modeling cancer diagnostics regulation by the FDA.
Authors: Richard Huang, Laura Lasiter, Christina Young, Jeff Allen, Jochen K Lennerz
Journal: Journal of Clinical Oncology (2020)

e14124 Background: VALID Act is a bipartisan draft legislation proposing to ensure the quality and safety of diagnostic tests through direct FDA oversight. Currently, FDA exercises enforcement discretion and exempts from premarket review tests that are developed and used in the same clinical laboratory. Many stakeholders have pointed out that the lack of direct FDA oversight has led to erroneous results that have serious patient consequences. However, the maintenance cost after the implementation of the Act is unknown. Thus, we estimate the additional financial burden of genotyping all new late stage cancer patients under a fully implemented VALID Act precertification framework. Methods: Based on our laboratory with 36 high-complexity clinical assays, we modeled the cost increase by dividing the total anticipated cost for annual FDA precertification by our 2019 patient volume. To model the stringency of complying with the Act, we calculated either 3, 6, or 9 assays as representative of the laboratory’s test complexity. To make the estimated additional annual national healthcare cost relatable, we expressed the increase as a distributed cost per newly diagnosed late stage cancer patient in 2019 (NCI SEER) or per employed person in 2019 (Bureau of Labor Statistics). Results: FDA precertification for 3 assays was estimated at $638,310.13, or when divided by our annual late stage patient volume (n = 10,232), an increased cost of $62.38/patient. Precertification for 6 or 9 assays costs $684,751.60 (+$66.92/patient) or $1,253,717.25 (+$122.53/patient), respectively. If only 1 cancer center per state/DC/PR got precertified (n = 52), multiplied by the cost of precertifying 3 assays, then the annual national healthcare cost would increase by $33,192,126.50, or +$42.37/new late stage patient (n = 783,476) or +$0.21/employed (n = 158,803,000). Precertification for 52 centers for 6 or 9 assays would cost $35,607,083.20 (+$45.45/patient, +$0.22/employed) or $65,193,297.00 (+$83.21/patient, +$0.41/employed), respectively. Nationally, there are ~886 centers and the increased cost was estimated at &lt; $7/employed. Even though the VALID Act will affect more than late stage cancer patients, thus costs will vary, our data show how a specific change of the Act will impact oncology practice. Conclusions: We provided a concrete cost model for late stage cancer patients under the proposed VALID Act. Cost modeling is important in informing the balanced legislative language needed to ensure patient access to validated cancer diagnostics, while supporting continued innovation by clinical laboratories.
Real-world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients.
Authors: Dirk Hempel, Florian Ebner, Valeria Milani, Wolfgang Janni, Amelie De Gregorio, Andreas Gaumann, Zeljka Trepotec, Arun Garg, Louisa Hempel
Journal: Journal of Clinical Oncology (2020)

e13005 Background: Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. The present study shows the retrospective analysis of our experience with NGS using a panel of 324 genes in combination with protein expression in patients with metastatic breast cancer (mBC) over the last 18 months. The primary objective of this study was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Methods: We analyzed 41 patients with advanced BC using solid tumor genomic profiling test. The test was used to detect clinically relevant genomic alterations (point mutations, indels, rearrangements, CNAs, tumor mutation burden (TMB) and microsatellite instability (MSI)) and to support the selection of appropriate targeted therapy. The protein expression (hormon receptors, ERBB2 and PDL1) of tumors was analyzed by immunohistochemistry (IHC). Results: The most common BC subtypes were HR+/ERBB2- (n = 20), followed by triple-negative (n = 15), and HER2+ BC (n = 9). 41 different genetic alterations were reported. Most patients had more than one genetic alteration (n = 27), as determined by NGS. The most common alterations were PIK3CA (n = 14), out of which 11 (78%) were hormone-receptor positive/ERBB2 negative. Conclusions: The NGS of mBC supports the decision for the most promising treatment option in 58,5% of our patients with a Tier I evidence. For an appropriate treatment decision it is necessary to evaluate gene alterations und protein expression of metastases in account. For an appropriate interpretation of rare gene alterations in mBC basket trials on basis of real world data are necessary. We founded the OnkoVision alliance to bring MTB into clinically routine and to identify appropriate patients for basket trials.
Efficacy and safety of alflutinib (AST2818) in patients with T790M mutation-positive NSCLC: A phase IIb multicenter single-arm study.
Authors: Yuankai Shi, Xingsheng Hu, Shucai Zhang, Dongqing Lv, Yiping Zhang, Qitao Yu, Lin Wu, Li Liu, Xiang Wang, Zhiyong Ma, Ying Cheng, Hongrui Niu, Dong Wang, Ji Feng Feng, Cheng Huang, Chunling Liu, Hui Zhao, Jingzhang Li, Xiaodong Zhang, Yong Jiang
Journal: Journal of Clinical Oncology (2020)

9602 Background: Alflutinib (AST2818) is a third generation EGFR-TKI. This phase IIb, multicenter, single arm study (ALSC003, NCT03452592) aimed to assess the efficacyand safety of Alflutinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC). Methods: Patients with locally advanced or metastatic EGFR T790M mutated NSCLC who progressed after first/second-generation EGFR-TKIs therapy or primary EGFR T790M mutation positive received 80 mg Alflutinib orally once daily. Tumor tissue samples underwent central laboratory testing for EGFR T790M mutation. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Efficacy was assessed by independent radiological review committee per RECIST 1.1. Safety was assessed by NCI CTCAE version 4.03. Results: From Jun 4, 2018 to Dec 8, 2018, 220 patients were enrolled with a median age of 61.0 (range 29 to 80) years. According to the AJCC version 8 staging system, 212 (96.4%) cases were in stage IV, and 8 (3.6%) cases in stage III. All patients had EGFR T790M mutation. By April 12, 2019, the ORR was 73.6% (95% CI 67.3–79.3). The DCR estimated at 6 and 12 weeks were 87.3% (95%CI 82.1-91.4) and 82.3% (95%CI 76.6-87.1), respectively. The median PFS was 7.6 months (95% CI 7.0–NA). Median OS and DoR have not been reached. 209 (95.0%) patients had at least one adverse events (AEs), which were mostly grade 1 or 2 and well tolerable. The most common AEs were increased aspartate aminotransferase (33 [15.0%]), upper respiratory tract infection (33 [15.0%]), and cough (33 [15.0%]). Grade 3 to 5 AEs occurred in 42 (19.1%) patients. The most common one was elevated γ-glutamyltransferase (n = 4). There were 3 deaths patients, 2 of which possibly not be related to the study drug, and 1 could not be determined. No interstitial pneumonia was reported. Conclusions: Alflutinib has promising efficacy and acceptable safety profile for the treatment of EGFR T790M mutated NSCLC patients. Clinical trial information: NCT 03452592 .
双向转诊案例分析
Authors: 杜雪平, 王青
Journal: BMJ (2011)

杜雪平:双向转诊有赖于医疗保险、国家医改政策和制度的完善,后面我会用实例分析双向转诊.第一个案例:患者男性,工人,60岁,发现高血压3年,最高可达180/130 mm Hg(1 mm Hg =0.133 kPa).一直在社区卫生站就诊,口服硝苯地平缓释片、酒石酸美托洛尔、盐酸苯那普利及中药,但血压仍在160～ 170/90～100 mm Hg,近日血压再次升高到180/120 mm Hg,社区医生以顽固性高血压转诊到复兴医院,以“高血压3级”收入院。
医院发展进入理念制胜时代
Authors: 吴春容
Journal: BMJ (2005)

医院从计划经济时代进入市场经济时代,面临改革与发展的诸多机遇和挑战,处于政策、信息、市场需求和理念瞬息万变的环境之中,医院的发展战略急需调整.在规模、设备、技术、专家方面开展竞争,以专科化发展为基础,滥用技术和药物,人的整体性和社会性得不到重视;在医疗资源过剩的同时,服务却严重不足;在技术服务过度的同时,人的需求、期望、感情、尊严却得不到应有的尊重;管理和服务过于机械化、单一化、失人性化、计划化和粗放化,人的个性化、多样化、多层次、深层次的需求得不到满足.医院如果完全按照计划经济时代的模式来经营,那就很难适应市场竞争的环境.做什么事情都是先有观念,观念是第一位的影响因素,转型时期的医院首先需要转变的就是观念或理念。