tbuckley/cabot-search huggingface dataset:
Clinical significance of serial tumor next generation sequencing (NGS) in 155 pediatric cancer patients.
Authors: Xiaonan Zhao, Marilyn M. Li, Jeff Schubert, Jinhua Wu, Fumin Lin, Gerald B Wertheim, Lea Surrey, Minjie Luo, Yiming Zhong, Chao Wu, Kajia Cao, Richard Aplenc, Rochelle Bagatell, Yael P. Mosse, Timothy S. Olson, Mariarita Santi, Sarah K. Tasian, Phillip Storm, John M. Maris, Stephen Hunger
Journal: Journal of Clinical Oncology (2020)

e13666 Background: Molecular profiling using NGS technology is critical for tumor diagnosis, risk stratification, and treatment selection. There are limited data in childhood cancers regarding evolution of genomic changes under the selective pressure of chemoradiotherapy. Here we report on serial testing of hematologic and solid pediatric tumor specimens across the spectrum of diagnosis, during treatment and disease relapse. Methods: Since 2016, 2,144 somatic NGS assays from 1,727 unique cancer patients were performed using the Comprehensive Hematological Malignancy Panel (CHMP) or the Comprehensive Solid Tumor Panel (CSTP). Serial tumor analysis was performed on 155 patients. All tumors were profiled for SNVs/indels, copy number alterations (CNAs), and fusions. The clinical impact on diagnosis, prognosis, and therapy was assessed. Results: 85 and 70 patients were tested with CHMP and CSTP, respectively. 86.5% (134/155) of patients underwent 1 subsequent genetic testing, while 13.5% (21/155) were serially tested for 3 - 6 times. Relapsed or therapy-refractory tumor was the most common indication for repeat CHMP and CSTP analysis of tumor genomics (64.5%, 100/155), primarily to survey for new targetable cancer driver mutations. The second most common reason for serial testing with CHMP was to monitor clonal evolution for patients with bone marrow failure syndromes and/or myelodysplastic syndromes, which resulted in a new cancer diagnosis in 14.6% (6/41) patients. For CSTP, the second most common reason for serial testing was to test a different part of the same tumor for tumors with histologic and/or radiographic heterogeneity (27.1%, 19/70). Of all patients with serial testing, 70 had at least one clinically significant new SNV/indel, 44 had distinct CNAs, and 4 had new clinically actionable fusions. Overall, clinically significant new results were detected in 81 (52.3%) patients, including 53 patients with new clonal changes indicating disease evolution, 31 of diagnostic significance, 9 of prognostic significance, and 8 suggesting new treatment options. Conclusions: Taken together, these data highlight the clinical importance of serial testing of pediatric tumors for potential biomarkers that may impact patients’ care at various time points across the spectrum of their diseases.
Utilization of next-generation sequencing and associated systemic therapy initiation in metastatic prostate cancer.
Authors: Daniel X. Yang, Michael Leapman, Cary Philip Gross, James B. Yu
Journal: Journal of Clinical Oncology (2020)

e19308 Background: There is emerging evidence for using clinical genomic classifiers for prognostication and to guide treatment choice in metastatic prostate cancer (mPC). While clinical-grade next generation sequencing (NGS) tests are increasingly available, how NGS has impacted systemic therapy selection for mPC is unclear. Methods: We performed retrospective observational study using the nationwide US Flatiron Health EHR-derived de-identified database. We identified patients with mPC diagnosed between January 1, 2013 and September 31, 2019. Receipt of NGS testing was chart-confirmed. “Short-interval” systemic therapy initiation in association with NGS testing was defined as line of therapy start within 30 days of documented NGS test result date. Results: A total 11548 mPC patients were included in our cohort, of which 1034 patients (8.9%) had documented NGS after metastatic diagnosis. There were 1210 documented NGS tests total, with 146 (14.1%) patients documented as undergoing NGS testing on more than one occasion. Median time from metastatic diagnosis to initial NGS test results was 560 days (IQR 194 to 1016 days). NGS test documentation increased from 7.1% of cases diagnosed in 2013 to 12.1% of cases diagnosed in 2017 (p &lt; 0.001). A new line of systemic therapy was initiated within 30 days for 207 NGS test results (17.1%). Although the percent of NGS tests associated with short-interval initiation of a new line of therapy increased from 11.1% in 2013-2014 to 16.5% in 2018-2019, the difference was not statistically significant (p = 0.540). The most common systemic therapies initiated within 30 days after NGS testing were docetaxel (18.8%), cabazitaxel (16.8%), and abiraterone (15.4%). Conclusions: While there has been an increase in documented NGS tests in mPC, rates of short-interval systemic therapy initiation after NGS did not change significantly from 2013-2019. Further study is needed as to whether this will increase in years to come, as well as potential improvements in clinical outcomes due to therapy change.
Treatment patterns of advanced or recurrent endometrial cancer following platinum-based therapy in the U.S. real-world setting.
Authors: Andrew J. Klink, Leslie DeMars, Joice Huang, Eric M. Maiese, Bruce A. Feinberg, Jean Hurteau
Journal: Journal of Clinical Oncology (2020)

274 Background: Patient (pt) prognosis is poor following disease progression on or after primary (1L) platinum-based therapy (PBT) for advanced/recurrent (A/R) endometrial cancer (EC), and no consensus on standard second-line (2L) therapy exists. This retrospective analysis aimed to understand real-world (RW) treatment patterns of pts with A/R mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC who progressed after 1L PBT. Methods: Physicians in Cardinal Health’s Oncology Provider Extended Network submitted retrospective data by abstracting outpatient electronic medical records of pts who received systemic treatment for A/R EC following PBT from 2016 to 2018. Demographics, clinical characteristics, treatments, and outcomes were summarized descriptively. Results: This study included 84 pts with A/R dMMR/MSI-H EC (table). The majority of participating physicians were hematologists/medical oncologists (80%) and practiced in the community setting (70%). Median duration of therapy (mDOT) in 1L was 4.9 months (95% CI, 4.47–5.57); 64% of pts discontinued treatment due to completion and 35% due to disease progression. In contrast, mDOT in 2L was 6.2 months (95% CI, 5.40–6.37); 37% of pts discontinued treatment due to completion and 44% due to disease progression. The most common MMR/MSI testing modalities were next-generation sequencing (NGS) only, immunohistochemistry (IHC) only, and polymerase chain reaction (PCR) only (table). Conclusions: RW treatment patterns in pts with A/R dMMR/MSI-H EC show that most will undergo PBT retreatment. However, progression is the main reason for discontinuation during retreatment. An urgent need exists for durable therapies that improve prognosis. Opportunities to improve timely testing of MMR/MSI exist. Funding: GlaxoSmithKline, Waltham, MA, USA. [Table: see text]
Association of traditional cardiovascular risk factors with venous thromboembolism
Authors: Yuan Liu
Journal: BMJ (2019)

Venous thromboembolism (VTE), including pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT), is a global health problem with a heavy disease burden. This article critically analyzes the association between traditional cardiovascular risk factors and VTE through a review of related studies in the past decade.


Key words: 
Venous thromboembolism; Pulmonary thromboembolism; Cardiovascular disease; Risk factors
痔的非手术治疗
Authors: 陈朝文
Journal: BMJ (2005)

痔的治疗方法繁多,随着医学的发展和对痔本质的研究,有些方法逐渐被淘汰,如Lord法主要依据痔发生的肛管痉挛和狭窄学说,随着对痔本质研究的深入,已弃用[1].20世纪80年代前,传统概念指导下痔的治疗,主要着眼于消除或破坏痔,或局部腐蚀性药物治疗,存在手术后并发症多等问题.自2000年开始,痔的研究出现了很多新进展,也出现了一些新的治疗方法,如药物治疗和吻合器痔上黏膜环形切除术(procedure for prolapse and hemorrhoids, PPH术)等.中华医学会肛肠外科学组总结既往诊断和治疗经验,制订了 ,推动了广大医师对痔的重视,也推动了痔的各项研究[2,3],改变了临床对痔注重手术切除的片面观点.对痔的深入研究使我们认识到痔是一种不可根治又易于复发的疾病,控制和缓解痔的症状是痔的治疗目的和基本原则,尤其对Ⅰ、Ⅱ度内痔和不能耐受手术治疗的患者,首先应采用包括药物治疗在内的非手术治疗.痔的非手术治疗因其痛苦小、治疗方便深受患者青睐.非手术治疗主要包括一般治疗、药物治疗和简单的器械治疗。
A case of hair follicle nevus
Authors: Zhonghua Gan, Bo Tang
Journal: BMJ (2018)

报道1例耳前毛囊痣病例。患者女性、15岁。出生时发现左耳前肉红色丘疹，如米粒大，无自觉症状。后缓慢长大，遂就诊。检查见左耳屏前0.5 cm×0.8 cm隆起，肤色，表面光滑，无毛。行手术切除治疗。术后病理检查诊断为毛囊痣。
Utilization and analysis of health services for children at a community health service center in Shenzhen
Authors: Neng-qing He, Xiao-bing Liao, Xue-yan Duan, Xu-ri Chen, Xiu-hu Wu, Peng-fei Li
Journal: BMJ (2013)

To explore the current status of children receiving primary health services at a community health service center in Shenzhen so as to provide references for the formulation of children health care policies. According to the patient electronic data in 2011, the clinical profiles were analyzed for children aged under 7 years seeking the advice of general practitioners(GPs)at Niuhu Community Health Service Center. Children aged under 7 years accounted for 12.4% of all subjects. The causes of seeing the GPs were as follows: acute upper respiratory infection(58.2%), acute bronchitis(14.9%), gastroenteritis(5.6%), trauma(3.3%)and dermatitis(3.2%). And no difference existed in the workload between pediatrists and surgeons, internists or herbalists. The common and frequent community diseases may be diagnosed and managed at a community health service center.


Key words: 
Community health services; Children
Evaluation of adaptive NK cells in ovarian cancer patients with cytomegalovirus (CMV) reactivation and systemic inflammation.
Authors: Erin Wesley, Locke Uppendahl, Martin Felices, Audrey Messelt, Devon Hunter-Schlichting, Heather Nelson, Laura Bendzick, Melissa Ann Geller
Journal: Journal of Clinical Oncology (2020)

e18062 Background: Cytomegalovirus (CMV) is a common infection associated with increased inflammation (c-reactive protein (CRP) upon reactivation during immunosuppression. CMV infection has been associated with a subset of NK cells (adaptive) that are long-lived, have enhanced cytotoxicity, and thought to contribute to cancer control. Previous evaluation of a retrospective study showed CMV + CRP + patients had significantly worse RFS and OS compared to CMV + CRP − patients who had the longest OS. These findings suggest CMV may be immunomodulatory and, without immunosuppressive effects of inflammation, may be protective. We are further evaluating for the presence of adaptive NK cells in the patients to evaluate if these populations of cells are drivers for the changes in outcomes. Methods: Serum and ascites (22 samples each) collected in a prospective study at the time of surgery for HGSOC were evaluated for CMV and inflammation. CMV status and systemic inflammation were measured by immunoassay for CMV immunoglobulin G (IgG), dPCR for CMV DNA and C-reactive protein (CRP). Samples were categorized as reactive or non-reactive for CMV and positive or negative for CRP (≤10, &gt; 10 mg/L). Adaptive NK cell percentages were analyzed using GraphPad Prims 8 and p-values ≤ 0.05 were considered statistically significant. Proteomic techniques to quantify adaptive NK cells, differences in NK cell maturation and cytotoxicity are in process for an additional 80 samples. Results: CMV reactive patients showed increased percentages of adaptive NK cells (NKG2C + CD57 + ) in the blood and peritoneal cavity compared to CMV negative patients. There is a trend in the presence of adaptive NK cells in patient samples that are CMV reactive and CRP positive compared to CMV nonreactive and CRP positive. Conclusions: Preliminary analysis shows a trend in presence of adaptive NK cells in both the blood and peritoneal cavity of these patients but analysis is ongoing.
Linezolid for treatment of nocardiosis in systemic lupus erythematosus: a case report and literature review
Authors: Lei Zhou, Lu Gong, Zong-fang Zhang, Xiao-min Du, Kun-kun Wang
Journal: BMJ (2011)

This report presented a case of disseminated infection with nocardia in lupus erythematosus (SLE) and reviewed the current literature. Nocardiosis was a rare, sometimes life-threatening opportunistic infection in SLE patients. The isolation and identification of pathogen was fundamental for the diagnosis of nocardiosis. Sulfonamides were traditionally the agent of choice for treatment of nocardiosis; while it must be given for several months even more than one year, particularly in patients with suppressed immune function. Issues regarding the drug resistance and the toxicity of sulfonamides in long-term therapy needed to be considered. Linezolid could be an effective agent for the treatment of nocardiosis, whether it could reduce the treatment course need to be further studied.

Key words: 
Lupus erythematosus, systemic;  Nocardia infections
Epitheliod sarcoma: Molecular insights into proximal versus classic variant.
Authors: Anna Maria Frezza, Luca Sigalotti, Elisa Del Savio, Davide Baldazzi, Marta Sbaraglia, Alberto Righi, Marco Gambarotti, Marta Barisella, Silvia Brich, Angelo Paolo Dei Tos, Silvia Stacchiotti, Roberta Maestro
Journal: Journal of Clinical Oncology (2020)

e23552 Background: Epithelioid sarcoma (ES) is an ultra-rare sarcoma with distinctive pathologic and clinical features, marked by the loss of the expression of the SWI/SNF chromatin remodeling complex subunit SMARCB1. The current WHO classification recognizes two ES subtypes, different by morphology, clinical behavior and outcome: the “classic-type” and “proximal-type” ES. This study is aimed to better understand the molecular grounds sustaining this difference, and to identify new potential treatment targets to personalize therapy in this rare disease. Methods: RNA sequencing profiling was conducted on FFPE samples. Functional annotation enrichment was evaluated through over representation and gene set enrichment analyses (GSEA). Inference of immune contexture was obtained through deconvolution and single sample GSEA (ssGSEA) approaches. Results: Twelve samples from 5 proximal-type ES and 7 classic-type ES were profiled, 10 naïve and 2 pre-treated with chemotherapy. Proximal variant samples featured an overepresentation of MYC activity signatures and of other signatures impacting on cell cycle, protein synthesis and chromatin metabolism. Pathways enriched in the classic variant included NOTCH/HEDGEHOG and immune system regulation (e.g. inflammatory, interferon alpha and interferon gamma). Accordingly, deconvolution and ssGSEA approaches predicted an increased immune infiltration in classic subtype samples, essentially involving T cells, as well as increased expression of HLA class I molecules. Conclusions: Different regulatory networks seem to contribute to the different biologic and clinical behavior of proximal and classic ES. These preliminary data suggest a potential greater sensitivity of proximal type ES to drugs targeting the cell cycle, whilst immune checkpoint inhibitors might have some activity in classic variant ES. Further studies are ongoing to validate these preliminary observations.
Clinical application of portable echocardiography system in acute paroxysmal dyspnea
Authors: 车琳, 赵明中, 罗明, 蒋金法, 邓兵, 李元玲, 王乐民
Journal: BMJ (2007)

目的 探讨便携式超声心动图仪在诊治急性发作性呼吸困难中的应用价值.方法 分析81例急性发作性呼吸困难患者的床边心脏超声检查资料,对同时完成便携式超声心动图仪和传统心脏超声仪检测的45例患者的资料进行分析.结果 45例患者2种心脏超声仪检测的二维成像符合率达100%.81例患者中,经心脏超声证实临床诊断74例(91.4%),经心脏超声纠正诊断6例(7.4%),误诊1例(1.2%).便携式超声心动图仪能即刻诊断心包积液,实时监护心包穿刺术的进行和监测积液量的变化.结论 便携式超声心动图仪检查能为急性发作性呼吸困难的诊治提供快速、明确的诊断信息,能参与并指导临床干预,增加临床干预的准确性、科学性和有效性,并使现场超声成为可能。
Community-based practice of early lung cancer screening with low-dose spiral computed tomography in Jiaxing city from Zhejiang Province.
Authors: You-cai Zhu, Wen xian Wang, Chunwei Xu, Gang Lan, Huafei Chen, Xiaofeng Li, Zhanqiang Zhai, Lichao Huang, Kaiqi Du, Meiyu Fang
Journal: Journal of Clinical Oncology (2020)

e13557 Background: As one of the most frequent malignant tumors in China, the morbidity and mortality of lung cancer remain high. Early diagnosis and normative treatment is the key to improve the prognosis of lung cancer. The aim of this study is to explore the practice of early lung cancer screening with low-dose spiral computed tomography (CT) based on the current situation in community health service, with integration of superior resources of medical institutions at all levels in Jiaxing City from Zhejiang Province. Methods: From Jan. 2017 to Dec. 2019, we screened 13491 (male 8783, female 4708) individuals high-risk population in selected communities of Nanhu District, Pinghu County and Haiyan County, Zhejiang Province, for early diagnosis of lung cancer with low-dose spiral CT combined with multidisciplinary comprehensive treatment models including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation and follow-up. Results: Screening resulted in a diagnosis of cancer in 27 participants. Of these participants, 24 cases of primary lung cancer, 1 case of lung metastasis, 1 case of breast cancer, 1 case of thyroid cancer. The morbidity of primary lung cancer is 224.53×10-5. There were 20 cases of Stage 0-Ⅰlung cancer accounting for 83.33% of all diagnosed primary lung cancer. Conclusions: Based on community health service, screening with LDCT could improve the early diagnosis rate of lung cancer in both smokers and nonsmokers with feasibility and validity, which could be applicable in qualified eligible medical centers and communities in China. It is not reasonable to exclude nonsmokers from screening with LDCT.
Analysis of the efficacy and safety of naloxegol administered to patients with cancer and opioid-induced constipation with laxative-inadequate response: A real-world 12 months of follow-up study.
Authors: Manuel Cobo Dols, Carmen Beato, Luis Cabezon-Gutierrez, Rodolfo Chicas Sett, Isabel Blancas, Francisco Javier García Navalón, José-Luis Fírvida Pérez, Gala Serrano Bermúdez, Pilar Togores, Ignacio Delgado, Alexandra Giraldo-Marín, Anna Librán-Oriol, Alfredo Paredes Lario, Pedro Sánchez Mauriño, Oliver Higuera, Diana Moreno, Antonio Javier Jiménez-López, Ibone Huerta-González, Almudena Sanz-Yagüe, Begoña Soler
Journal: Journal of Clinical Oncology (2020)

e24155 Background: Naloxegol is a peripherally acting, µ-opioid receptor antagonist for treatment of opioid-induced constipation (OIC). The main objective of this study was to analyze the efficacy and safety of naloxegol in patients with cancer in a real-world 12-month follow-up study. Methods: An observational prospective study was conducted in 16 Spanish centers. Patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky ≥ 50 were selected. OIC with inadequate response to treatment with laxative (s) was the main diagnostic. All the patients received treatment with naloxegol according to clinical criteria. Efficacy was measured by the response rate and symptoms evolution measured by means of PAC-SYM questionnaire. Intensity of pain was measured by a 0-10-point visual analogue scale (VAS). Intent to treat last observation carried forward was applied. Results: A total of 126 patients were included in the study. About 58.7% were men, with a mean age of 61.5 years (34-89). Lung cancer was observed in 35.7%, breast cancer in 16.7%, 10.3% digestive cancer and 8.7% had prostate cancer. About 67.5% had metastases. Naloxegol at doses of 25 mg/day was administered to 88.1% and with concomitant laxatives in 48.4%. At 12 months, 77.8% of the patients were responders to naloxegol treatment: 78.6% at doses of 12.5 mg/day, and 78.4% with 25 mg/day. Furthermore, response was observed in 78.5% of patients without concomitant laxative treatment and 77% of patients with any concomitant laxative. PAC-SYM total score and all the dimensions improved from baseline (p &lt; 0.0001). VAS pain intensity was reduced and controlled from baseline onwards (Baseline-12 months: 4.6 to 3.6, p &lt; 0.001). A total of 28 adverse reactions mainly gastrointestinal were observed in 15.1% of the patients (19/126), 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) were observed the first 15 days of treatment with naloxegol. Conclusions: The results of this first real-world-data study in patients with cancer confirm the long-term efficacy of naloxegol for the treatment of OIC in this group of patients. Naloxegol is safe and well tolerated in patients with cancer while maintaining pain control.
Outcomes in patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression treated with immune checkpoint inhibitor monotherapy: An FDA-pooled analysis.
Authors: Sujay Yogesh Shah, Jonathon Joseph Vallejo, Yutao Gong, Thomas D. Brown, Chenan Zhang, Jonathan Hirsch, Shenghui Tang, Gideon Michael Blumenthal, Harpreet Singh, Paul Gustav Kluetz, Marc Robert Theoret, Julia A. Beaver, Richard Pazdur
Journal: Journal of Clinical Oncology (2020)

9606 Background: Higher PD-L1 score ≥ 50% predicts for greater benefit to immune checkpoint inhibitor (ICI) therapy in first line (1L) treatment of aNSCLC. It has recently been reported that PD-L1 score ≥ 90% predicts for even greater benefit to 1L ICI monotherapy (Aguilar et al., 2019). We examined pooled clinical trial databases to examine the relationship between high PD-L1 expression across multiple ICI monotherapies in 1L and second line (2L) treatment of aNSCLC. Methods: Data was pooled from trials (five 1L and five 2L) of ICI for the treatment of patients with aNSCLC. We defined PD-L1 score as the proportion of tumor cell stained by the assay (total of four assays identified) and included patients in the analysis with PD-L1 score ≥ 50%. Tumor-infiltrating immune cell staining was not considered. Progression-free survival (PFS) and overall survival (OS) by line of therapy for patients with PD-L1 score ≥ 90% and patients with PD-L1 score 50-89% was analyzed. Results: A total of 1320 patients treated with ICI monotherapy were identified, 873 in 1L and 447 in 2L. Median follow-up was 9.6 months in 2L patients and 13.3 months in 1L patients. Patients receiving 2L ICI therapy with PD-L1 score ≥ 90% (N = 208) had longer PFS and OS compared to patients with PD-L1 score 50-89% (N = 239), with mPFS 7.1 vs. 4.2 months (HR = 0.66 [95% CI: 0.52-0.83]) and mOS NR vs. 15.8 months (HR = 0.66 [95% CI: 0.49-0.89]). 1L ICI therapy analysis revealed similar trends, as patients with PD-L1 score ≥ 90% (N = 405) had longer PFS and OS compared to patients with a PD-L1 score 50-89% (N = 468), with mPFS 8.3 vs. 5.4 months (HR = 0.78 [95% CI: 0.66-0.92]) and mOS 22.9 vs. 16.4 months (HR = 0.74 [95% CI: 0.61-0.90]). Conclusions: This analysis showed the potential of an enhanced clinical benefit in patients with aNSCLC and PD-L1 score ≥90% across ICI monotherapies in both the 1L and 2L treatment setting. These data will be further analyzed in real world populations.
Long-term survival following multivessel revascularization in patients with diabetes The FREEDOM Follow-On Study: the FREEDOM follow-on study
Authors: Michael E Farkouh, Michael Domanski, George D Dangas, Lucas C Godoy, Michael J Mack, Flora S Siami, Taye H Hamza, Binita Shah, Giulio G Stefanini, Mandeep S Sidhu, Whady Armindo Hueb
Journal: Journal of the American College of Cardiology (2019)