tbuckley/cabot-search huggingface dataset:
Comparative study between image-guided percutaneous biopsies and matched surgical specimens for the evaluation of PD-L1 status in non-small cell lung cancer.
Authors: Liang Zhao, Haojun Chen, Kaili Fu, Yanzhen Zhuang, Qin Lin
Journal: Journal of Clinical Oncology (2020)

e15168 Background: Programmed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS)between biopsies and matched surgical specimens remains controversial. This study aimed to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens. Methods: We evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen’s kappa (κ) coefficient. Results: Immunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 83.3% (115/138), and the κ value was 0.73 (95% CI: 0.63–0.83, P &lt; 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy (88.6% [62/70, κ value: 0.81] vs 77.9% [53/68, κ value: 0.66]). Conclusions: PD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy. [Table: see text]
胰岛素泵的剂量设定和调整
Authors: 刘娟, 李延兵
Journal: BMJ (2011)

胰岛素泵治疗是采用人工智能控制的胰岛素输入装置,通过持续皮下输注胰岛素的方式,模拟胰岛素的生理性分泌模式,从而控制高血糖的一种胰岛素治疗方法.胰岛素泵多采用半自动的调节方法,事先设置好不同时段的基础量,使其自动输入,每日餐前量可根据进餐种类和总量临时设置.作为一种胰岛素注射手段,胰岛素泵最明显的优势在于其胰岛素剂量调整的灵活性,可自由调整剂量,通过基础率的分段设置、不同类型餐前量追加方式以及校正大剂量和补充大剂量的补充功能对血糖进行精细调整,此外,与多次皮下注射相比,胰岛索泵还具有降低低血糖发生率,减少血糖波动,提高患者生存质量以及节省胰岛素用量的优点.长期胰岛素泵治疗主要用于1型糖尿病(T1DM)、器官移植后患者和需要长期使用胰岛素强化治疗的2型糖尿病( T2DM)患者。
急性有机磷中毒患者阿托品应用探讨
Authors: 杜长军
Journal: BMJ (2005)

快速实现阿托品化是急性有机磷中毒(AOPP)重要治疗手段之一,但若不能正确识别阿托品化,滥用阿托品,则可能会导致阿托品中毒甚至死亡.据报道阿托品中毒发生率为40%～60%[1],死亡率为18.3%[2].作者根据其治疗AOPP的实践经验和学习体会,对阿托品应用问题讨论如下。
Trends of skeletal related events in patients with breast cancer metastasized to bone.
Authors: Prasanth Lingamaneni, Ishaan Vohra, Krishna Rekha Moturi, Muhammad Zain Farooq, Sheeba Habeeb Ba Aqeel, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

1098 Background: Up to three-quarters of women with advanced breast cancer develop bone metastases, predisposing to Skeletal Related Events (SRE), which are associated with a significant health care burden, poor prognosis, loss of functional independence and a decrease in quality of life. We performed a retrospective analysis on predictors of SRE in this population. We also evaluated temporal trends of outcomes and resource utilization in those with SRE. Methods: Adult breast cancer patients with metastases to bone, admitted from January 2012 to September 2015 were identified from the Nationwide Inpatient Sample database. Based on previous studies, SRE was defined by using ICD-9 codes for pathologic fracture, spinal cord compression, necessity for radiation to bone or surgery to bone. Multivariable analysis of predictors of SRE in patients with breast cancer metastatic to bone, as well as mortality in the SRE group were performed. Temporal trends of resource utilization across the years were evaluated. Results: A total of 143,455 patients with breast cancer with metastases to bone were identified, of which 17.2% had SRE. Patients with SRE had a mean age of 66 years and were predominantly white (70.2%). After adjusting for confounders, African Americans and Hispanics were less likely than Whites to develop SRE. On multivariable analysis, only comorbidity burden (in the form of high Charlson comorbidity index) predicted inpatient mortality. Rates of SRE in breast cancer patients with bone metastases did not change over the years (17.2% to 17.1%). Inpatient mortality of patients with SRE remained stable (3.76% to 3.79%). There was a statistically significant increase in surgical intervention (43.4% to 47.7%, p&lt;0.01) and decrease in radiation to bone (25.7% to 19.7%, p&lt;0.001) over time. Length of hospital stay and total hospital charges, after adjusting for inflation, remained largely unchanged. Conclusions: Incidence of SRE, inpatient outcomes and health care costs remained stagnant in those with metastatic breast cancer between 2012 and 2015, despite the advent of novel bone-targeted agents. There has been an increased trend towards surgical intervention and less utilization of local radiation over time. [Table: see text]
Ephesus: A curation workflow tool for the clinical interpretation of genomic variants.
Authors: Jian Li, Lili Niu, Nicole Greene, Vivian Douglas, Caitlin Schartner, Bernie Chu, Fnu Kinshuk, John Mu, Austin Doupnik, Andi Broka, Priyanka Rao, Marghoob Mohiyuddin, Shuba Krishna
Journal: Journal of Clinical Oncology (2020)

e14074 Background: Accurate and comprehensive interpretation of genomic variants has become a bottleneck in clinical sequencing applications due to the accelerated implementation of precision oncology and the rapid growth of relevant biomedical findings. We therefore are motivated to build Ephesus, a framework enabling curation of clinical evidence for biomarkers in somatic cancers. Currently Ephesus is the primary content source for Roche NAVIFY Mutation Profiler (NMP). Methods: Ephesus’ data model ensures adherence to best practice in clinical genomic content curation. Variant classification followed the AMP guidelines for somatic variant interpretation. Approvals and recommendations from regulatory agencies and organizations (FDA, NCCN, etc.) are applied on a regional basis. The data model is mapped to a set of PostgreSQL relational tables. Strategies such as data normalization according to standard ontologies, a submit-review-approval workflow with change logs, and biologically relevant datatype constraints are adopted to enforce data integrity. Ephesus is deployed as a web application, of which the UI allows users to conduct edits, filtering, sorting and bulk operations on entities by attributes. To maximize curation efficiency, a number of inference rules are applied before the content is ingested into NMP. Results: Currently Ephesus is developed to guide data collection, browsing and summarizing related to these primary entities: Biomarkers, Evidence items, Genes, Variants, Variant groups, and Drugs. The content exported on 2020/01/27 contains &gt; 170K biomarker profiles (including combinations), in the context of 13 major cancer types. To evaluate the clinical reporting value of the curated knowledge, more than 60k real clinical cancer patient samples from the AACR GENIE project were queried against Ephesus. We compared the results to the latest content from several major knowledgebases. We see that the performance of Ephesus/NMP excels the others. Conclusions: We have developed Ephesus, a practical content curation framework which provides a highly structured and user-friendly environment for clinically relevant somatic biomarkers. The framework improved the productivity and quality of the manual curation, met clinical interpretation scope and complexity, and assures data integrity and auditability. [Table: see text]
CD56<sup>bright</sup>/CD16<sup>bright</sup> NK-cell adoptive immunotherapy in patients with concurrent CNS disease and relapsed or refractory (R/R) AML.
Authors: Lucia Silla, Alessandra Paz, Vicente Odone Filho, Nelson Hamerschlak, Rosane Bittencourt, Dean Anthony Lee
Journal: Journal of Clinical Oncology (2020)

3025 Background: Patients (pts) with R/R AML and concurrent CNS disease rarely respond to chemotherapy and have a dismal prognosis. Adoptive immunotherapy (AI) with haploidentical ex vivo-activated/expanded NK cells shows promise in R/R AML, but it is unknown whether the blood–brain barrier (BBB) represents an obstacle to this approach. Here we present data from 4 pts with CNS disease from a phase 1 study of 13 pts receiving NK AI for R/R AML (NCT02809092). Methods: Double bright (CD56 bright /16 bright ) activated NK cells (DBNK) were expanded from haploidentical family donors on feeder cells expressing membrane-bound IL-21. DBNK were infused thrice weekly for six doses 3–7 days after fludarabine, cytarabine, and G-CSF (FLAG). Pts received doses ranging from 10 6 to 10 7 DBNK/kg/infusion. CNS responses at day 30 were assessed using Response Assessment in Neuro-Oncology criteria. RNA sequencing was used to compare gene expression in DBNK vs unexpanded NK cells. Results: Demographics of the 4 pts with CNS disease are shown (Table). All pts had received a prior stem cell transplant and were heavily pretreated (median 6 prior treatments), and 1 had primary refractory disease. All pts completed 6 NK-cell infusions without dose-limiting toxicities. No cytokine storm syndrome was reported. Other toxicities were manageable, including CNS hypertension symptoms. Imaging studies showed inflammation localized to disease sites. All 4 pts showed a response (Table), with complete, long-lasting resolution of CNS lesions documented in pts #1 &amp; #5, almost complete resolution of bone and nerve root leukemic infiltration in pt #4, and a 50% reduction of CNS chloromas in pt #6. Responses were durable, lasting up to 7 months. DBNK showed upregulation of homing receptors associated with CNS trafficking. Conclusions: Multiple infusions of ex vivo IL-21-expanded DBNK were tolerable and demonstrated unprecedented CNS responses in patients with R/R AML. These data support effectiveness of DBNK across the BBB. Clinical trial information: NCT02809092 . [Table: see text]
Deep learning to develop transcriptomic model for survival prediction in TCGA patients with hepatocellular carcinoma.
Authors: Hao Yu, Wei Dai, Chi Leung Chiang, Shisuo Du, Zhao-Chong Zeng, Guo-Ming Shi, Wei Zhang, Albert Chan, Chen Hu, Feng-Ming Kong
Journal: Journal of Clinical Oncology (2020)

e14057 Background: This study aimed to investigate the prognostic value of transcriptome and clinical data of Hepatocellular carcinoma (HCC) patients for overall survival (OS) by deep learning method. Methods: A total of 371 HCC patients with 20530 level three RNA-sequencing data were from The Cancer Genome Atlas (TCGA). Cox-nnet model, a deep learning model through an artificial neural network extension of the Cox regression model, was used for OS prediction. The patients were randomly split into train-set and test-set (7:3). In train-set, the significant genes associated with OS under univariate Cox regression were considered for modeling. Clinical parameters, including age, gender, pathologic stage, child pugh classification, creatinine level etc. were also considered. The Cox-nnet model was developed by cross-validation. Its discrimination was determined by the concordance index (CI) in the independent test-set and compared with multivariable Cox regression. The clustering method Uniform Manifold Approximation and Projection (UMAP) was used for revealing biological information from the hidden layer in the model. Results: In the train-set (n = 259), 1505 genes and two clinical variables (child pugh score and creatinine level) were significantly associated with OS (adjusted P-value &lt; 0.05). To avoid overfitting, only 40 most significant genes were included in the Cox-nnet model. In the test-set (n = 112), the CI of Cox-nnet (0.76, se = 0.04) is better than the CI of multivariable Cox regression (0.71, se = 0.05). The difference between good or poor survival subgroups classified by Cox-nnet was remarkably significant ( P-value = 1e-4, median OS: 80.7 vs. 25.1 months). In the Cox-nnet model with all significant variables, the weights in the hidden layer were clustered by UMAP into 3 positive clusters and 2 negative clusters, which are enriched in GO/KEGG. The “cell cycle” and “complement and coagulation cascades” are the most important signal pathways in positive and negative clusters, respectively. Conclusions: Combining transcriptomic and clinical data, and with deep learning algorithm, we built and validated a robust model for survival prediction in HCC patients. Our study would be useful to explore the clinical implications in survival prediction and corresponding genetic mechanisms. Clinical trial information: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA1438.
《中华医学会首届全国社区卫生服务中心主任论坛》会议纪要
Authors: 李兆晖
Journal: BMJ (2008)

由卫生部、科技部、中国科协主办的中华医学会首届全国卫生服务中心主任论坛于2008年4月27-28日在北京召开,来自北京、天津、上海、石家庄等城市社区卫生服务主管领导、社区卫生服务中心主任、社区医生等200余人参加。
Comprehensive breast cancer (BC) risk assessment for CHEK2 carriers incorporating a polygenic risk score (PRS) and the Tyrer-Cuzick (TC) model.
Authors: Shannon Gallagher, Elisha Hughes, Allison W. Kurian, Susan M. Domchek, Judy Ellen Garber, Braden Probst, Brian Morris, Placede Tshiaba, Eric Thomas Rosenthal, Benjamin Roa, Susanne Wagner, Alexander Gutin, Jeffrey N. Weitzel, Jerry Lanchbury, Mark E. Robson
Journal: Journal of Clinical Oncology (2020)

1504 Background: Women with pathogenic variants in the moderate penetrance CHEK2 gene have on average an estimated &gt; 20% lifetime risk for breast cancer, thereby meeting an established threshold for more aggressive screening, including consideration of breast magnetic resonance imaging (MRI). However, we previously showed that CHEK2 penetrance is modified by an 86-SNP PRS. CHEK2 risk is further modified by family history (FH) and other TC model variables. Here, we describe development of a comprehensive risk prediction model for women of European ancestry to more precisely estimate risk by incorporating CHEK2, PRS and TC V7.02. The number of CHEK2 carriers with low ( &lt; 20%), moderate (20%-50%) and high ( &gt; 50%) remaining lifetime risk based on the combined model was examined in an independent study cohort. Methods: This IRB-approved study included de-identified clinical records from 358,471 women of European ancestry who were tested clinically for hereditary cancer risk with a multi-gene panel. Model development was based on analysis of CHEK2 PV carriers ( N= 4,331) and women negative for BC gene PV ( N =353,681) who were tested between September 2013 and July 2019. Risk estimates incorporating CHEK2, PRS and TC were calculated using a fixed-stratified (FS) method that accounts for correlations between risk factors in a manner equivalent to multivariable co-estimation. Risk stratification was assessed in an independent cohort of CHEK2 carriers ( N= 459) who were tested after July 2019 and not included in model development. Results: We detected significant correlation of CHEK2 status with FH ( p= 4.1 × 10 −17 ) and of PRS with FH among CHEK2 carriers ( p= 1.7× 10 −5 ). For these factors, joint effects were co-estimated using the FS method. In an independent cohort, 24.0% of CHEK2 carriers were categorized as low risk ( &lt; 20%), and 62.6% were categorized as moderate risk (20-50%). For 13.4% of CHEK2 carriers, risk estimation incorporating PRS and TC generated BC risks of greater than 50%, consistent with genes recognized as highly penetrant. Conclusions: In CHEK2 PV carriers, comprehensive risk assessment could inform individualized decision-making and may lead to improved targeting of screening and prevention strategies.
Professional medical writing assistance in oncology clinical trials.
Authors: Joseph Abi Jaoude, Ramez Kouzy, Walker Mainwaring, Timothy Lin, Austin B. Miller, Amit Jethanandani, Andres F. Espinoza, Cullen M. Taniguchi, Ethan B. Ludmir
Journal: Journal of Clinical Oncology (2020)

e14088 Background: Academic publishing remains the cornerstone of biomedical research and scientific communication. Researchers often assign professional medical writers (PMWs) to craft publications, as these individuals may improve the overall writing quality and/or reduce time to publication. We sought to characterize the landscape of PMW utilization in phase III cancer clinical trials. Methods: We searched ClinicalTrials.gov for phase III randomized clinical trials between the years 2003 and 2018. Randomized multi-arm trials assessing a therapeutic intervention in cancer patients were included. After identifying the corresponding publications, we identified whether a PMW was involved in writing the manuscript based on author disclosures, along with any related funding information. Results: Six-hundred oncology RCTs with corresponding manuscripts were identified. In total, 260 (43.3%) trials used a PMW. Financial support to medical writers was largely provided by the industry (247/260, 95.0%). In multivariate analyses, PMW utilization was higher among industry-funded trials compared to non-industry-funded trials (OR: 14.2, p= 0.001). PMWs were used more frequently to report successful trials that met their primary endpoint (OR: 1.8, p= 0.03) but did not differ between English-speaking and non-English-speaking countries ( p= 0.19). Cooperative group trials used PMWs with less frequency compared to non-cooperative groups (OR 0.68, p &lt; 0.001). PMWs were used more often in trials that led to subsequent drug FDA approval (69.6% vs 40.6% in trials that did not lead to subsequent FDA approval), but this association did not reach statistical significance in multivariate analysis ( p = 0.744). The use of PMWs has increased significantly over time (OR: 1.11/year, p =0.001). Conclusions: In this analysis, we show a strikingly high prevalence of PMW utilization in phase III oncology trials, with a vast majority of industry-supported studies using PMWs. We believe that professional writing assistance plays an important role in clear and efficient scientific communication. However, the disproportionate role of PMWs in reporting positive, industry-funded trials may represent a conflict of interest. We urge continued and increased reporting of utilization and funding of professional writing assistance in cancer clinical trials.
Relevance of bisphenol A and polycystic ovary syndrome
Authors: Jian-ye Fang, Jing Yang, Tai-lang Yin, Nan Yu, You-min Mo
Journal: BMJ (2013)

To explore the relationship and possible mechanism of reproductive function of bisphenol A (BPA) with polycystic ovary syndrome (PCOS). Serum specimens were collected from 43 PCOS patients and 37 healthy women. And the level of BPA was detected by enzyme-linked immunosorbent assay (ELISA). The serum level of BPA in PCOS were significantly higher than that in the control group. And the inter-group difference was significant (P 0.05). Although no difference existed between insulin and non-insulin resistance, the level of BPA in insulin resistance group was lower than in non-insulin resistance group. A higher level of BPA may be associated with obesity and basic LH in PCOS.


Key words: 
Bisphenol A; Polycystic ovary syndrome
Man or machine: who is more important?
Authors: 曾昭耆
Journal: BMJ (2007)

在基层的医务人员,常因为所在单位的规模小、设备差而感到工作困难.这个不利条件显而易见,希望增添一些必要的设备也是可以理解的. 近年来,随着国家对基层医疗保健工作的重视,一些地方政府向基层医疗保健机构投入了大量资金,增添了一些设备,条件有所改善.但是,事实上不可能也不必要达到大医院那样的规模.正因为如此,就应该特别深刻地认识到强化医生基本功锻炼的重要性。
Immunological changes with perception of cold in breast cancer (BC) patients.
Authors: Shipra Gandhi, Maithreyi Sarma, Kristopher Attwood, Christine B. Ambrosone, Elizabeth A. Repasky, Chi-Chen Hong
Journal: Journal of Clinical Oncology (2020)

e12559 Background: Tumor-bearing mice “feel colder” than non-tumor bearing mice and prefer to be at thermoneutral temperatures. Cold stress results in immunosuppressive tumor microenvironment [decrease in CD8 + T-cells, increase in myeloid derived suppressor cells and T-regulatory cells]. Cytokines play a significant role in modulating these immune cells. Breast cancer (BC) patients frequently report feeling excessively cold under ambient temperature. We examined the association between cytokine levels and thermal discomfort symptoms in BC patients in the Women’s Health After Breast Cancer (ABC) Study treated at Roswell Park Comprehensive Cancer Center. Methods: 424 stage I-III BC patients were identified. Standard demographics, body mass index (BMI), race, grade, histological subtype, tumor size, stage, nodal status, treatment received, and menopausal status were recorded. Peripheral blood was prospectively collected at diagnosis and one year post diagnosis and analyzed for a panel of 27 cytokines. Patients completed a questionnaire reporting symptom of “feeling cold when others are fine” using a Likert scale one year post BC diagnosis. Relationships between cytokines levels as tertiles and symptoms of “feeling cold” were evaluated using logistic regression. Change in cytokine levels from the time of BC diagnosis to one year post were also evaluated [ &gt; 20% decrease, no change (-20 to +20%), and &gt; 20% increase]. Results: Overall, 195/424 (46%) patients reported “feeling cold”. There were no differences in patient and tumor characteristics between patients who reported “feeling cold” vs “not cold.” Interestingly, 53.4% patients on chemotherapy reported “feeling cold” (p &lt; 0.05). At baseline, higher IL-17E and IL-6 were associated with decreased perception of feeling cold (p &lt; 0.05, p &lt; 0.01). At one year post diagnosis, higher TNF-β was associated with decreased perception of feeling cold (p &lt; 0.05). Changes in IL-22 and IL-33 were associated with increased perception of feeling cold (p &lt; 0.05, p &lt; 0.05). Multivariate model adjusted for age, race, BMI, histological subtype, stage, grade, treatment and menopausal status showed a trend towards decreased cold perception with higher IL-6 but was not statistically significant. Conclusions: We observe significant differences in pro-tumorigenic IL-6 and anti-tumorigenic IL-17E &amp; TNF-β cytokines in BC patients reporting thermal discomfort. This suggests avenues for using thermal therapies to modulate inflammatory cytokine production in breast cancer.
Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia
Authors: Jayakumar Vadakekolathu, Mark D. Minden, Tressa Hood, Sarah E. Church, Stephen Reeder, Heidi Altmann, Amy H. Sullivan, Elena J. Viboch, Tasleema Patel, Narmin Ibrahimova, Sarah E. Warren, Andrea Arruda, Yan Liang, Thomas H. Smith, Gemma A. Foulds, Michael D. Bailey, James Gowen-MacDonald, John Muth, Marc Schmitz, Alessandra Cesano, A. Graham Pockley, Peter J. M. Valk, Bob Löwenberg, Martin Bornhäuser, Sarah K. Tasian, Michael P. Rettig, Jan K. Davidson-Moncada, John F. DiPersio, Sergio Rutella
Journal: Science Translational Medicine (2020)

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)-γ-related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ-dominant AML subtypes.