tbuckley/cabot-search huggingface dataset:
Serum concentrations of sCD40L in patients with acute ischemic cerebrovascular diseases
Authors: Dong-fang Li, Xue-jun Xie, Guang-lai Li, Wei-min Hu, Guo-fang Xue, Juan Li
Journal: BMJ (2009)

One hundred patients with acute ischemic stroke were enrolled in the study as the trial group, and 20 healthy individuals as control group. Intima-media thickness and plaque of the carotis were detected by carotid ultrasonography, cerebral infarction was detected by CT/MRI, and serum concentrations of sCD40L were measured by enzyme-linked immunosorbent assay. Neurologie impairment score was evaluated in all patients. The results showed that in patients with acute ischemic stroke the serum concentrations of sCD40L in plaques group were significantly higher than those in no plaque group. The levels of serum sCD40L of infarction group (diameter>1.5 cm) were higher than those of lacunar infarction group ( diameter<1.5 cm ) and temporary ischemic attack ( TIA ) group. The levels of serum sD40L in trial group were all higher than those in control group. In the trial group, serum concentrations of sCD40L were correlated with neurologic impairment score. The results indicate that CD40/CD40L signaling pathway may be involved in the carotid atherosclerosis formation and the rupture of plaques, and the increase of serum CD40L levels might be a risk factor for acute ischemic cerebrovascular diseases.

Key words: 
Cerebrovascular disorders; CD40L
Comparison of genomic instability test scores used for predicting PARP activity in ovarian cancer.
Authors: Kirsten M Timms, Gordon B. Mills, Michael Perry, Alexander Gutin, Jerry Lanchbury, Robert Brown
Journal: Journal of Clinical Oncology (2020)

1586 Background: Clinical trials have explored the utility of various genomic instability (GI) scores or gene panels to assess deficiencies in the homologous recombination (HR) DNA repair pathway and support PARP inhibitor use in ovarian cancer; however, these methods of assessing homologous recombination deficiency (HRD) may not be equivalent. The myChoice HRD test is the only analytically and clinically validated, FDA-approved HRD test that includes BRCA1/2 mutation status and three measures of GI. We compared the proportion of patients identified as candidates for PARP inhibitor use by two measures of HRD [percent loss of heterozygosity (%LOH), 11-gene panel] to myChoice HRD. Methods: Whole-genome SNP analysis was used to reconstruct ovarian tumor genomic profiles to calculate the myChoice HRD score and %LOH in 2 cohorts (clinical laboratory cohort, N = 3,278; SCOTROC4 trial, N = 248). Mutation screening for a set of 11 genes in the HR pathway ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D) was performed for a subset of tumors from the SCOTROC trial (n = 187). Samples were considered positive if the myChoice HRD score was above the threshold (threshold scores of 42 and 33 were assessed), %LOH above the threshold (16%), or a pathogenic variant in one of the 11 HR genes. The correlation between positive results from %LOH and the 11-gene panel were compared to myChoice HRD. Percent positive agreement (PPA) was the proportion of positive test results from myChoice HRD that were also positive by %LOH or the 11-gene panel. Results: The table shows the correlation and PPA between myChoice HRD, %LOH, and the 11-gene panel. Overall, 19%-61% of patients identified as positive by myChoice HRD would have been missed by %LOH or the 11-gene panel in these two cohorts. Conclusions: These data show that HRD tests used in published and ongoing clinical trials are not equivalent, and they should not be considered interchangeable in predicting PARP inhibitor response in clinical practice. [Table: see text]
雷尼替丁致过敏反应24例
Authors: 包森和, 陈高梁, 刘志勤
Journal: BMJ (2005)

第二代H2受体拮抗剂雷尼替丁由于疗效确切,价格低廉,目前仍广泛应用于临床,特别是基层医院.但口服雷尼替丁也有过敏反应出现,我们对1996年1月至2003年12月在临床中发现的24例雷尼替丁致过敏反应总结报道如下。
Histopathologic validation of the sentinel node technique in early-stage cervical cancer patients.
Authors: Patrice Mathevet, Benedetta Guani, Andrea Ciobanu, Eliane Mery Lamarche, Florent Boutitie, Vincent Balaya, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2020)

6028 Background: Sentinel lymph node biopsy (SLN) could be an alternative to systematic lymphadenectomy in early cervical cancer. SLN is less morbid and had shown a high sensitivity for metastasis detection. However, sensitivity of the SLN technique could be over evaluated because SLN are examined with ultrastaging and non sentinel nodes are only examined with routine techniques. The aim of this study was to validate the negative predictive value (NPV) of the SLN technique, with ultrastaging of SLN and non sentinel nodes (NSLN). Methods: We used the SENTICOL 1 study data, published in 2011. All nodes, SLN and NSLN have been secondarily subjected to ultrastaging. The ultrastaging consisted in sectioning every 200 µm and immunohistochemistry. A central reviewing of the positive slides and 10% of the negative slides was undertaken. Results: One hundred thirty-nine patients were included. SLNs were detected in 136 (97.8%) of the 139 patients. SLNs were found bilaterally in 104 (76.5%) of the 136 patients. 2056 NSLNs were identified (median = 13 NSLNs per patient [range 1-54]). Of 136 patients with SLNs detection, 23 had positive SLNs, after serial sectioning and IHC. NSLNs were metastatic in 8 patients. However, in case of bilateral SLN detection, the FN rate was 1/99 (1%) with detection of ITC in one NSLN from 99 bilateral negative SLNs. The NPV was 99% (0,99 [IC 95% = 0,97-1,00]). Conclusions: The pelvic SLN technic is a safe and trustfully technic to determine the nodal status in patients with early-stage cervical cancer. In case of optimal mapping with bilateral detection, NPV is 99% (IC 95% = 0,97-1,00).
Role of palliative radiotherapy in patients with metastatic colorectal cancer: A propensity score matching analysis.
Authors: Zhenyu Lin, Li Ba, Jinghua Ren, Tao Zhang
Journal: Journal of Clinical Oncology (2020)

e16043 Background: To explore whether palliative radiotherapy can further improve overall survival (OS) of patients with metastatic colorectal cancer (mCRC) receiving systemic treatment and analyze its survival prognostic factors. Methods: The demographics, tumor characteristics, and survival outcomes of 484 mCRC patients who underwent systemic treatment with or without palliative radiotherapy from December 2014 to September 2019 were analyzed. A propensity-score model was used to compare the group of patients receiving systemic treatment plus palliative radiotherapy (PR) or simple systemic treatment (ST). Results: There were 334 ST patients and 154 PR patients in total, and 288 cases (144 cases/group) after paired matching. The OS (1 year, 2 years, 3 years) in PR group were 73.6%, 40.3%, 16.0% and, respectively, which were higher than those in ST group (61.1%, 22.9%, 6.9%). The median survival times were 50.8 months and 32.2 months, respectively (P = 0.003). Multivariate analysis showed that the site of primary tumor, patient surgery status, local treatment of metastasis as well as whether or not radiotherapy are independent prognostic factors of survival time. Conclusions: We definitely demonstrated that palliative radiotherapy on the basis of systemic chemotherapy is expected to increase OS in mCRC patients. Left colon, primary surgery, local treatment of metastasis and radiotherapy are the independent prognostic factors of mCRC.
Driving quality improvement: How clinical decision support can facilitate compliance with evidence-based pathways.
Authors: Debra A. Patt, Bo He, Jody S. Garey, Paul Rowan, Michael D Swartz, Stephen Linder, Barry Don Brooks, Marcus A. Neubauer
Journal: Journal of Clinical Oncology (2020)

2045 Background: Cancer care is changing rapidly with more detailed understanding of disease and more numerous therapeutic choices. As treatment choice is more complex, mechanisms to improve compliance with evidence based treatment can improve the quality of cancer care. Methods: A retrospective cohort study was conducted from January 2014-May 2016 evaluating the impact of a clinical decision support system (CDSS) on compliance with evidence based pathways (EBP) across 9 statewide community based oncology practices. These EBP are developed with physician input on efficacy toxicity and value and incorporated in to a CDSS that is used within the Electronic Health Record (EHR) at point of care to alter the choice architecture a clinician sees when prescribing therapy. A multi-level logistic regression model was used to adjust for group effects on physician or practice behavior. SAS 9.4 software was used and GLIMMIX was applied. Individual physician benchmark compliance was evaluated using McNemar's test. Results: Regimen compliance with EBP was measured pre- and post- implementation of the CDSS tool across a large network encompassing 9 statewide practices and 633 physicians who prescribed over 30,000 individual patient treatment regimens over a 6 month period. The CDSS that is incorporated within the EHR significantly improved compliance with EBP across the entire cohort of practices, and in individual practices (see Table). Individual oncologists reached a target of 75% compliance more often (58% vs 72%) after implementation of the tool (p &lt; 0.001). Conclusions: CDSS is a tool that improves compliance with EBP that is effective at improving targets of compliance broadly, at the practice, and at the individual clinician level. Clinical informatics solutions that influence physician behavior can be inclusive of physicians in design, iterative in process, and nudge as opposed to force clinician behavior to drive quality improvement. These clinical informatics solutions grow in importance as the complexity of cancer care continues to increase and we seek to improve upon the quality and value of care delivery. [Table: see text]
Health disparity in Central Valley of California: Higher incidence of breast cancer in Asian population.
Authors: Soujanya Sodavarapu, Kate Hatter, Megha Goyal, Prakash Ramdass, Majed Sayedi, Nashwan Obad, Amandeep Singh Gill, Dinesh Vyas
Journal: Journal of Clinical Oncology (2020)

e19029 Background: California has the most immigrants of any state in the U.S., with approximately a quarter of the residents being foreign-born. The impact of migration on breast cancer incidences over time has not yet been characterized in the Northern Central Valley. This provides a unique opportunity to study the influence of migration, socioeconomic gradient, and racial identity on the incidence of breast cancer in San Joaquin County. Methods: This study was a retrospective, single-institution study that compared the socio-demographic variables and clinical characteristics of the patients who had a history of breast cancer in a teaching central valley hospital. We reviewed all charts with a breast cancer diagnosis from 2014-2019. We compared age, demographics, socioeconomic status comorbidities, pathology, treatment, and outcomes. Appropriate statistics have been used to analyze the data. Results: A retrospective chart review of all patients with a diagnosis of breast cancer from 2014-2019 at a central valley teaching hospital. 33.5% were white, 17.2% African American, 26.6% Hispanic, and 22.6% were Asian. Migrated Asian women are having three times increased incidence in central California compared to their peers in Asian. Additionally, those of lower socioeconomic status were more often affected (61.9% vs. 30.4% of middle-class status) in our population. Demographics and comorbidities were studied. Smoking was seen in 23.2% of patients, alcohol in 16.3%, hypertension in 43.6%, Diabetes in 18.9%, lung disease in 11.7%, and Kidney disease in 6.9%. 23.8% of the patients had a family history of cancer. Screening was only done in 41% of patients, and the distribution of race was as follows: white 10.6%, African American 7.7%, Hispanic 8.9%, Asian 8.9%. It was found that infiltrating ductal carcinoma was seen in 54.8% of patients, of which 16.1% were white, 10% African American, 15.5% Hispanic, and 13.2% were Asian. Triple-negative breast cancer was seen in 14.9% in our patient population. We further reviewed treatment methods, including chemotherapy, radiation, and surgery, as well as recurrence rates. Conclusions: We suggest that screening has to be more concentrated in all communities. The fact that the Asian population in the Central Valley shows higher rates of breast cancer could be due to epigenetic, western lifestyle, and environmental factors. Higher awareness and willingness as a subgroup may be contributing as well or there may be an actual increase; this requires further investigation, and we will present further subgroup analysis at presentation.
Monitoring of therapeutic efficacy to CDK4/6 inhibitors and early detection of metastatic relapse in breast cancer by ultra-deep sequencing of plasma cell-free DNA.
Authors: Yoon Ming Chin, Tomoko Shibayama, Masumi Otaki, Hiu Ting Chan, Makiko Ono, Yoshinori Ito, Shunji Takahashi, Shinji Ohno, Takayuki Ueno, Yusuke Nakamura, Siew-Kee Kee Low
Journal: Journal of Clinical Oncology (2020)

e15544 Background: CDK4/6 inhibition substantially improves progression-free survival for women with advanced estrogen receptor-positive breast cancer. Despite this, most patients experience acquired resistance. The analyses of cancer specific genomic aberrations in plasma cell free DNA, or commonly referred to as ‘liquid biopsy’, has generated immense interest. The role of liquid biopsy enables monitoring of therapeutic efficacy to detect relapse in a minimally invasive manner. It would drastically impact risk stratification, treatment selection and patient clinical outcome in advanced stage breast cancer. Methods: We have recruited consecutive patients with metastatic breast cancer who received CDK4/6 inhibitor treatment in combination with endocrine therapy between April 2018 and December 2019. Somatic mutations identified by the Oncomine Pan-Cancer cell free assay were used to assess the mutation profiles of circulating tumor DNA (ctDNA) by ultra-deep sequencing (~56,000 depth) of the plasma DNA. Plasma samples (N = 146) were collected before and during treatment (2 years) or until disease progression. Paired white blood cells (WBC) were also sequenced to exclude clonal hematopoiesis-derived mutations. Results: Twenty-eight patients were enrolled. Based on RECIST criteria, 1 patient showed complete response (CR) within 18 months of treatment, 5 patients showed partial response (PR) 6-18 months from start of treatment, 9 patients showed stable disease (SD) condition within 3-18 months and 13 patients developed progressive disease (PD) within 1-12 months. In 22 of 28 patients (79%), ctDNA was detected prior to start of treatment (12 responders; 10 PD) and used as a monitoring marker. Majority of mutations detected in pre-treatment samples were TP53, PIK3CA and ESR1. Among the 12 ctDNA positive responders, ctDNA levels of 9 patients were undetectable within 2 weeks to 6 months from start of treatment (median 3 months). ctDNA profiles were more reflective of clinical response compared to the tumor markers CEA and CA15-3. In 7 of the 10 PD patients with ctDNA monitoring markers, ctDNA showed higher sensitivity to predict disease progression compared to tumor markers that remained stagnant or below normal threshold. ctDNA also predicted PD earlier than radiological images with a median lead time of 3 months. Conclusions: ctDNA assessment for therapy monitoring and early relapse detection in advanced breast cancer is feasible and provides a basis to evaluate early therapeutic interventions.
Barriers to prescribing targeted therapies for NSCLC patients with highly actionable gene variants in the VA National Precision Oncology Program.
Authors: Vishal Vashistha, Jenna Armstrong, David Winski, Meghan Price, Bradley J. Hintze, Pradeep Poonnen, Jane Snowdon, Gretchen Purcell Jackson, Dilhan Weeraratne, David Brotman, Neil L. Spector, Michael J. Kelley
Journal: Journal of Clinical Oncology (2020)

2005 Background: Next-Generation Sequencing (NGS) gene panels are often completed to guide therapeutic decisions for patients with advanced stage non-small cell lung cancer (NSCLC). Patients with highly-actionable gene variants may experience improved therapeutic treatments and reduced toxicities with use of targeted agents. Ensuring appropriate prescription of targeted therapies is therefore of high importance. We sought to identify barriers to targeted agent use within the Veterans Health Affairs’ (VHA) National Precision Oncology Program (NPOP). Methods: A retrospective evaluation examined the cohort of NSCLC patients who underwent NGS multi-gene panels through NPOP between July 2015 and February 2019. A level of evidence for drug actionability was assigned to each observed oncogenic gene variant using an artificial intelligence offering (IBM Watson for Genomics: WfG). WfG level 1 and 2A evidence was reviewed by NPOP staff to exclude gene variants that did not conform to NPOP level 1 and 2A definitions. Anti-neoplastic drug prescriptions and oncology provider notes were obtained for all included patients from the VHA Corporate Data Warehouse. Review of clinical notes of patients who did not receive targeted agents was performed to categorize the reason(s). Results: Of 1764 NSCLC patients who successfully underwent NGS gene panel testing, 156 (8.9%) received therapeutic level 1 (7.3%) or 2A (1.6%) options for targeted agents based on WfG evidence analysis. In total, 117 (6.6%) patients had NPOP level 1 and 2A gene variants, all within ALK, BRAF, EGFR, ERBB2, MET, and RET. Of these, 49 (41.2%) patients were not prescribed available targeted agents. The three most common reasons were: (1) treating provider did not comment on NGS results (30.7%), (2) patient did not carry a diagnosis of advanced stage disease (18.4%), and (3) patient had begun an alternative systemic therapy prior to completion of sequencing (16.3%). No patient was denied access to a level 1 or 2A targeted drug due to utilization-management review. Conclusions: A substantial minority of patients with advanced NSCLC bearing highly-actionable gene variants are not prescribed available targeted agents. Further provider- and pathologist-directed educational effort are needed, as well as implementation of health informatics systems to provide near real-time decision support for test ordering and interpretation.
Colin Ralston Paterson
Authors: Elspeth Paterson, Suzanne Christie, Robert Paterson
Journal: BMJ (2020)

Colin Ralston Paterson was born in Manchester and won scholarships to Shrewsbury and Brasenose College, Oxford, where he worked with Hans Krebs. He subsequently trained at University College Hospital London and in Leeds and York, before moving to Dundee in 1969. His work focused on metabolic …
Preferences and motivational factors for the use of digital technology in real world oncology studies.
Authors: Nadeeka Dias, Rinah Yamamoto, Kenneth G Faulkner
Journal: Journal of Clinical Oncology (2020)

e14119 Background: Patient engagement and motivation during real world oncology studies can be challenging. Digital tools have proven to be effective in reducing patient burden and improving data collection and accuracy. Given the rapid advances in health technology, patient preferences and motivations for these tools are continually evolving. This study investigates preferences for digital technology use with smartphones and wearables, telehealth, and identifies motivational factors that would drive real world study compliance for daily symptom reporting. Methods: Patients (n = 50; 68% male) diagnosed with cancer answered questions via an anonymous online survey about their technology preferences. Results: Although the majority of the population uses smartphones (99%), few oncology patients use wearable technology such as a fitness watch (18%). Of those who do not own a fitness watch, 90% were willing to use the technology in a clinical study and share their data if a watch were provided to them. However, the majority of patients (74%) would prefer to use their own smartphone during a clinical study to answer questions and conduct video calls with the study doctor. For patients who currently visit their doctor in person (98%), almost half (48%) would prefer a remote alternative such as a video call for convenience, especially when in pain. Patients reported several factors that would encourage consistent daily reporting of study data. Out of 10 options, the most motivating factor was access to health information that would help manage their symptoms on a daily basis (92%). Subsequent factors of interest included in-app reminders (88%) and assurance that a doctor would review the reported data and contact them to discuss reported symptoms (94%). Conclusions: The global market for digital health is growing rapidly, and there is a strong preference from oncology patients to shift in-person engagement and reporting to digital platforms. Patients are also highly motivated by information about their own health. Designing real world studies to incorporate these preferences may result in enhanced patient engagement, improved compliance, and higher quality data.
“Through others we become ourselves”: The dialectics of predictive coding and active inference
Authors: Dimitris Bolis, Leonhard Schilbach
Journal: Behavioral and Brain Sciences (2020)

Abstract Thinking through other minds creatively situates the free-energy principle within real-life cultural processes, thereby enriching both sociocultural theories and Bayesian accounts of cognition. Here, shifting the attention from thinking-through to becoming-with, we suggest complementing such an account by focusing on the empirical, computational, and conceptual investigation of the multiscale dynamics of social interaction.
清热降浊汤联合依达拉奉对急性脑梗死患者超敏C反应蛋白水平的影响
Authors: 周雄根, 钱义明, 朱亮
Journal: BMJ (2011)

我科采用清热降浊法联合依达拉奉治疗急性脑梗死,报告如下. 1.对象与方法:我院急诊科2010年1月至8月收治急性脑梗死患者60例,诊断均符合全国第四届脑血管学术会议修订的标准[1],并经头颅CT和MRI证实.入选患者1～3个月内均无急性创伤、感染、风湿等疾病史,无明显肝、肾功能异常,无肿瘤病史。