tbuckley/cabot-search huggingface dataset:
Clinical activity and safety profile of dacomitinib in advanced epidermal growth factor receptor-positive non-small cell lung cancer patients with brain metastases.
Authors: Jinyao Zhang, Shouzheng Wang, Ke Yang, Puyuan Xing, Li Junling
Journal: Journal of Clinical Oncology (2020)

e21656 Background: Dacomitinib is a second-generation epidermal growth factor receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) which has been shown to be superior to first-generation EGFR TKI, gefitinib in both progression- free survival and overall survival outcomes in EGFR+, non-small cell lung cancer (NSCLC) patients in a Phase III, randomized study, ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases (BM). To our knowledge, this is the first chart review which describes dacomitinib’s activity in the CNS in a real-world setting. Methods: 24 patients who were receiving dacomitinib (30 mg daily) for advanced NSCLC harboring EGFR sensitive mutations, either Exon 19 deletion or Exon 21 L858R substitutions were included in this study. Hospital chart was retrospectively reviewed to identify patients with baseline brain metastases (n = 6). Treatment outcomes of these patients who were presented with baseline brain metastasis were analyzed. Results: Among the 6 patients, median age was 54.5 years (range, 41-74), 4 were male, ECOG PS 0 and 1 were 1 and 5, respectively. All of them had non-squamous NSCLC with asymptomatic BM and 5 with no measurable BM lesion. One patient had dose reduction due to drug-related adverse events. One patient has not reached the 4-week RECIST assessment at data cut-off. The intracranial ORR and DCR among 5 response- evaluable patients with at least one follow-up disease assessment were 40% and 100% (2/5 complete response, 3/5 stable disease). All patients are having ongoing treatment (median follow-up:3-months). Patients experienced low-grade (G1/2) toxicities which are reversible, including diarrhea, rash, paronychia and stomatitis. Conclusions: This chart review suggests, for the first-time, that dacomitinib may have CNS efficacy in patients with untreated EGFR+ NSCLC in the real-world setting. Due to the small number of patients included in this chart review, the findings need to be confirmed in future studies.
儿童肥胖--父母应该了解些什么
Authors: 刘岚
Journal: BMJ (2004)

儿童肥胖是指儿童体重超过其标准体重的20%.据美国疾病与预防控制中心(CDC)的数据表明,20世纪60～80年代美国儿童和青少年超重的流行状况基本稳定,但在随后的20年里其数量却翻番,没有任何下降的趋势.超重青少年数量戏剧性上升的后果是,一些以前只在成人才被诊断的疾病,也开始在孩子们中出现了,如:睡眠呼吸暂停综合征,2型糖尿病,高血压,动脉粥样硬化。
血压的晨峰现象及其临床意义
Authors: 郭艺芳, 胡大一
Journal: BMJ (2007)

人体血压存在典型的近日节律(或称昼夜节律,circadian rhythm),并且这种节律现象具有重要临床意义.研究表明,高血压患者血压波动的昼夜节律特征与靶器官损害及心血管终点事件的发生具有密切关系,而血压的晨峰现象尤为如此.在降压治疗的同时充分关注血压的晨峰现象,有效抑制清晨时段的血压上升速度与幅度,可能有助于最大程度地降低心血管事件的危险性。
Predictors of successful randomized phase III studies in the treatment metastatic renal cell carcinoma: A meta-analysis.
Authors: Justin Lin, Xiaobo Zhong, Matt D. Galsky, William K. Oh, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e17105 Background: The success of randomized phase III therapeutic trials (RP3TT) to reach their primary endpoint is critical given the enormous resources required to conduct such studies. In an era of accelerated therapeutic development in advanced kidney cancer, we aim to identify factors in such studies associated with a positive endpoint (PE) to better understand how to optimize trial design. Methods: Using PubMed and ClinicalTrials.gov, we identified all published RP3TT in patients with metastatic renal cell carcinoma between 1/2007-9/2019. Studies were considered PE if the primary endpoint was reached, and negative endpoint (NE) if otherwise. Studies were categorized as either first line only (FLO) or second line and beyond (SLB), with adjuvant and consolidation therapy studies excluded. We collected components of study design and baseline patient characteristics and analyzed with multivariate logistic regression to evaluate the associations between each factor and PE RP3TT. Results: Of the 65 studies evaluated, only 22 RP3TT (14 FLO, 8 SLB) were found to have published data and were included, with 14 PE and 8 NE. For all studies, those with larger enrollment size (OR = 1.008, 95% CI [1.001-1.015], p = 0.021) and clear cell requirements (OR = 0.077, 95% CI [0.007-0.901], p = 0.041) were associated with PE. After adjusting for sample size, only larger enrollment size remained significant (OR = 1.007, 95% CI [1.001-1.014], p = 0.032). Other baseline patient demographic and clinical characteristic variables were not associated with PE RP3TT. Subgroup analysis of only FLO or SLB studies also did not yield any significant associations with PE RP3TT. Conclusions: Higher enrollment size was identified as factor associated with PE in RP3TT. Incomplete trial data reporting was evident, particularly in earlier studies. Further efforts are needed to better characterize factors in order to optimize clinical trial design in this disease. [Table: see text]
Additional gene mutations may refine the 2017 European LeukemiaNet classification in adult patients with de novo acute myeloid leukemia aged &lt;60 years
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Alice Mims, Deedra Nicolet, Christopher J. Walker, James S. Blachly, Andrew J. Carroll, Dimitrios Papaioannou, Jonathan E. Kolitz, Bayard E. Powell, Richard M. Stone, Albert de la Chapelle, John C. Byrd, Krzysztof Mrózek, Clara D. Bloomfield
Journal: Leukemia (2020)
A phase I dose escalation and expansion study of the next generation oral SERD AZD9833 in women with ER-positive, HER2-negative advanced breast cancer.
Authors: Erika Paige Hamilton, Mafalda Oliveira, Udai Banerji, Cristina Hernando, Javier Garcia-Corbacho, Anne Armstrong, Eva Ciruelos, Manish R. Patel, Jason Incorvati, Chris Twelves, Tim Brier, Danielle Carroll, Steven Fox, Teresa Klinowska, Justin P O Lindemann, Richard Mather, Rhiannon Maudsley, Sam McGuinness, Andy Sykes, Richard Baird
Journal: Journal of Clinical Oncology (2020)

1024 Background: AZD9833 is an oral selective estrogen receptor (ER) antagonist and degrader (SERD) that has shown antitumor efficacy in a range of preclinical models of breast cancer. Methods: SERENA-1 (NCT03616587) is an ongoing Phase 1, open-label study in pre- and post-menopausal women, after ≥1 endocrine therapy and ≤2 prior chemotherapies for ER+ HER2- advanced breast cancer (ABC). The primary objective is to determine the safety and tolerability of AZD9833 once daily (QD), with dose-limiting toxicities (DLTs) in 28d defining the maximum tolerated dose. Secondary objectives include pharmacokinetics and anti-tumor response. Pharmacodynamic (PD) analysis includes ER modulation in paired tumor biopsies and ctDNA dynamic changes. Results: At 20 January 2020: 60 patients were treated (median prior therapies 5 (1–9); prior fulvestrant (Fv) 82%; prior CDK4/6i 68%) across five doses; 25 mg QD n=12, 75 mg QD n=12, 150 mg QD n=13, 300 mg QD n=13, 450 mg QD n=10. AZD9833 exposure was dose proportional after multiple doses, with a median terminal t1/2 of 12h. Treatment-related AEs experienced by ≥10% of patients were visual disturbances (53%; 91% G1, 6% G2, 3% G3), bradycardia/sinus bradycardia (45%; 93% G1, 7% G2), nausea (18%; 46% G1, 55% G2), fatigue (13%; 38% G1, 63% G2), dizziness (10%; 83% G1, 17% G3) vomiting (10%; 50% G1, 33% G2, 17% G3), and asthenia (10%; 67% G1, 33% G2). Three patients experienced DLTs: G3 QTcF prolongation (300 mg); G3 vomiting (450 mg); and a combination of G2 visual disturbance, G2 headache and G2 gait disturbance (450 mg). DLTs resolved with dose reduction. No G4 or 5 AEs were reported. Efficacy data are presented in the table below; objective response rate (ORR) and clinical benefit rate (CBR) at 24 weeks. Clinical trial information: NCT03616587 . ER signalling pathway modulation was observed in all dose cohorts. In patients where clinical responses occurred and paired biopsies obtained, 98% reduction in Ki67 was measured. Updated data will be presented. Conclusions: AZD9833 has an encouraging efficacy and dose-dependent safety profile. Evidence of clinical benefit and target engagement was observed at all dose levels in women with ER+ ABC, including patients pre-treated with CDK4/6i and Fv, and those with ESR1 mutations. A Phase 2 study comparing efficacy and safety of three doses AZD9833 vs Fv is planned (NCT04214288). [Table: see text]
结核菌纯蛋白衍生物强阳性在新生体检中的应用
Authors: 程建英
Journal: BMJ (2007)

结核菌纯蛋白衍生物(简称TB-PPD)是结核菌肉汤培养物加热灭菌后,浓缩过滤液的沉淀物,被广泛应用于结核病的诊断及结核病疫情的监测.2004年开始,北方工业大学连续2年在新生入学体检中增加了TB-PPD监测项目.作者对此进行分析。
Safety and effectiveness of medical cannabis as a complementary option for supportive cancer care: Results from the Cannabis Pilot Project.
Authors: Antonio Vigano, Saro Aprikian, Popi Kasvis, Virginie Bacis, Amna Al Harrasi, Nathalie M Aubin, MariaLuisa Vigano, Manuel Borod
Journal: Journal of Clinical Oncology (2020)

12106 Background: Access to medical cannabis (MC) is a common request by patients and caregivers in supportive cancer care (SCC). However, healthcare professionals require more evidence on MC safety and effectiveness. Methods: The Cannabis Pilot Project (CPP) was implemented at the Cedars Cancer Centre of the McGill University Health Centre to evaluate MC as a complementary option for symptom control in SCC. Referral to the CPP was reserved for patients who were receiving SCC but had not obtained adequate symptom relief. An interdisciplinary team (physician, nurse and research coordinator) was established to systematically assess patients, prescribe and monitor MC treatments and record data on their safety and effectiveness. Patients were enrolled in the CPP between February 2018 and December 2019 and reassessed at intervals of one to six months. Results: Ninety-six cancer patients (mean age 60.0y (±13.9); 41 (42.7%) males) had at least one follow-up (FUP) and were included in the study. The main cancer types were breast (19.8%), lung (9.4%) and colorectal (9.4%). Adverse events (top three: drowsiness, low energy and nausea) were reported in 28% of patients, with 9% having to stop MC. Mean Brief Pain Inventory scores significantly improved between baseline, FUP-2 and FUP-3 for worst pain (5.4± SEM 0.3 vs 4.3±0.3 and 3.7±0.4) and average pain severity (4.2±0.2 vs 3.2±0.3 and 3.2±0.4). Anorexia improved (3.4±0.3 vs 2.2±0.4 and 1.7±0.4), as measured via the revised Edmonton Symptom Assessment System (ESAS-r). ESAS-r wellbeing improved significantly between baseline and FUP-1 (4.4±0.2 vs 3.7±0.2). Between baseline and each FUP, approximately a third of patients dropped their use of concurrent medications (including analgesics, antidepressants and anxiolytics), as measured by the Medication Quantification Scale. Conclusions: The CPP data support the safety and effectiveness of MC as a complementary option for improving pain control, appetite and quality of life in SCC.
Effect of botulinum toxin A on tibial nerve F wave and walking ability in patients after stroke
Authors: Mingle Wang, Junfang Liu
Journal: BMJ (2015)

Sixty five stroke patients undergoing rehabilitation training in our hospital from May 2010 to May 2013 were randomly divided into study group (n=32) and control group (n=33). Patients in study group received intramuscular injection of botulinum toxin A (BTX-A) in the affected limbs before rehabilitation training started. The F wave amplitude and F/M value, muscle tension and TUG test and 10 m free walking test results of patients in two groups were observed before and 4 weeks after treatment. Compared to the results before treatment, the amplitude of F wave and F/M value after 2 and 4 weeks of treatment in study group decreased significantly (P 0.05); while TUG test and 10 m free walk test in study group were better than those in control group after 4 weeks of treatment (P 0.05). The results indicate that botulinum toxin A injection can reduce amplitude of F wave in the corresponding segment of spinal cord motor neurons and improve the walking ability of stroke patients.


Key words: 
Botulinum toxin type A; Cerebrovascular accident
A multi-gene colorectal cancer liquid biopsy with &gt;90% accuracy in diagnosis and assessment of disease status.
Authors: Irvin Mark Modlin, Mark S. Kidd, Alexandra Kitz, Ignat A. Drozdov, Anna Malczewska, Katarzyna Kusnierz, Harry Aslanian
Journal: Journal of Clinical Oncology (2020)

e16079 Background: There are few blood-based biomarkers for colorectal cancer (CRC). We report a 13-gene colon cancer circulating-free mRNA to diagnose CRC. Clinical utility was assessed in surgical and chemotherapy patients. Methods: Gene identification/validation: Publicly available colon cancer transcriptomes (E-MTAB-57) to identify candidate markers using gene co-expression network enrichment, differential expression and functional enrichment analyses. Cell line/tumor tissue gene expression: Candidate gene expression was evaluated in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and surgical resection samples (CRC adenocarcinomas: n= 33) and biomarkers validated in the TCGA-COAD database ( n= 261 adenocarcinomas, 41 mucinous adenocarcinomas). Blood gene expression: CRC set (cancers: n= 312, controls n= 117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n= 37, follow&gt;7 days. Chemotherapy: n= 75; stable disease (SD): n= 20, progressive disease (PD): n= 55). The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis: Thirteen candidate CRC genes blood were identified. Cell lines and tumor tissue: Expression levels were significantly elevated ( p&lt; 0.001, 20-100-fold) in cell lines and CRC tumors. All 13 markers were confirmed in TCGA-COAD samples (average TPM ranged from 692-4405). Blood gene expression: All 13 CRC marker genes were identified in CRC blood. Levels were 54.4±1.5 ( p&lt; 0.0001) compared to controls (9.5±1.7); AUROC:0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). The matched tissue/blood correlation was r = 0.80 ( p= 0.002). Clinical Utility: In the surgical cohort, accuracy was 100% vs CEA (35%) or CA-19-9 (17%) (both p&lt; 0.0001). Resection (R0–92%) significantly decreased levels (47±2) at follow-up ( p&lt; 0.006). In the treated cohort, levels were elevated in PD (63±4.1) vs SD (30±3.2, p&lt; 0.0001). Conclusions: A CRC gene marker panel in blood identified colon cancer with a diagnostic accuracy of 91%. This was significantly greater than CEA or CA-19 in CRCs. Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy will facilitate image-based management.
Impact of neoadjuvant chemotherapy on survival in women with endometrial cancer: A National Cancer Database analysis.
Authors: Laura Chambers, Xuefei Jia, Mariam Alhilli
Journal: Journal of Clinical Oncology (2020)

e18094 Background: To evaluate overall survival (OS), prognostic factors for survival, and treatment outcomes in patients with Stage III/IV endometrial cancer (EC) undergoing neoadjuvant chemotherapy +/- surgery compared to surgery followed by adjuvant chemotherapy. Methods: The National Cancer Database (NCDB) was queried to identify patients with Stage III/IV EC who were treated with chemotherapy. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for OS. Survival was measured from date of diagnosis to the date of last contact or death. Results: From 2004-2012, 31,726 women with stage III/IV EC were identified. . Treatment groups consisted of: 3424 (10.8%) chemotherapy alone (C), 26926 (84.9%) surgery followed by chemotherapy (S+C), and 1412 (4.4%) neoadjuvant chemotherapy followed by surgery (NACT+S). The median age at diagnosis was 64 years (19-90), and 65.8% (n = 35402) of patients had Stage III disease. Reasons for no surgery were: not part of primary treatment plan (77.7%; n = 5859), contraindicated due to patient factors (11.3%, n = 850) or patient refusal (3.6%; n = 268). The majority of patients (86.8%) received multiple chemotherapy agents and 1988 (6.3%) received single agent chemotherapy. Charlson-Deyo score was 0 for 75.3% (n = 2578) of C, 76.7% (n = 20652) of S+C and 77.8% (n = 1098) of NACT+S patients (p &lt; 0.001). Compared to patients who received C alone, S+C and NACT+S were associated with improved median OS (10.9 months vs. 63.3 (HR 0.27 CI 0.26-0.28, p &lt; 0.001) and 24.6 months (HR 0.50, 95% CI 0.47-0.54, p &lt; 0.001), respectively). On multivariate analysis advanced age (HR 1.03, p &lt; 0.001), stage IV disease (HR 2.70, p &lt; 0.001), Charlson Deyo Score (1 – HR 1.13, p &lt; 0.001; 2 – HR 1.32, p &lt; 0.001), and African American race (HR 1.53, p &lt; 0.001) were associated with worse OS.Private insurance (HR 0.87, p &lt; 0.001), income &gt; $63,000 (HR 0.86, p &lt; 0.001) and treatment with S+C (HR = 0.32, p &lt; 0.001) or NACT+S (HR 0.44, p &lt; 0.001) versus C alone were predictive of improved OS. Conclusions: In this analysis of the NCDB, receipt of chemotherapy alone is associated with markedly worse OS than S+C or NACT +S in stage III/IV patients. . Socioeconomic factors including African American race, insurance status and income are independent predictors for survival in this cohort. Where feasible, surgery should be should be incorporated into treatment planning for women with Stage III/IV EC.
Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs
Authors: Min Hyung Ryu, Kevin Soon-Keen Lau, Denise Jill Wooding, Shuyu Fan, Don D Sin, Christopher Carlsten
Journal: Thorax (2020)

Rationale Exposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways. Methods Fourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators. Results In human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p&lt;0.005), eotaxin-3 (p&lt;0.0001), interleukin 5 (IL-5; p&lt;0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV 1 . Conclusion Short-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion. Trial registration number NCT02017431 .
Open-label, randomized, multicenter, phase IV trial comparing parenteral nutrition using multi-chamber bags (Eurotubes) versus traditional 2/3-chamber bags in subjects with metastatic or locally advanced inoperable cancer requiring parenteral nutrition: The PEKANNUSS trial of the AIO.
Authors: Georg Martin Haag, Ralf-Dieter Hofheinz, Jann Arends, Thorsten Oliver Goetze, Ingeborg Roetzer, Hubert Serve, Daniel Pink, Florian Weissinger, Dirk M. Behringer, Thomas Zander, Kim Barbara Luley, Ludwig Fischer von Weikersthal, Frank Lammert, Walter Dallacker, Janine Kreiss-Sender, Buleza Koci, Daniel Wilhelm Mueller, Claudia Pauligk, Yara Strehler, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2020)

TPS7086 Background: Approximately 50% of all cancer subjects suffer from cancer anorexia-cachexia syndrome accompanied by an inadequate food intake and predicting mortality, poor therapeutic response, diminished functional capacity, and reduced QoL. Especially in the advanced stages, parenteral nutrition (PN) is often required and accompanied by an increased risk of blood stream infections associated with increased mortality and other serious medical conditions such as sepsis. Furthermore, the switch from oral food intake to PN changes the patient’s everyday life leading to reduced autonomy and flexibility (e.g. due to dependency on home nursing services). This study aims at evaluating the incidence of catheter-related infections (CRI) and the frequency of self-administered parenteral nutrition at home (HPN) in patients receiving standard PN via A) traditional two- or three-chamber bags (often requiring addition of vitamins and/or medications by home care service) or B). the multi-chamber bags Eurotubes (minimizing additional supplements and enabling self-administration by patients at home). In addition, one group of patients will receive low glucose HPN via Eurotubes to investigate a possible benefit on clinical outcome. Methods: This is an open-label, randomized, multicenter, investigator-initiated, phase IV trial. Overall, 350 patients with inoperable metastatic or locally advanced solid tumors who have an indication for parenteral nutrition will be enrolled. Patients will be randomized 1:1:1 ratio to Arm A (Standard PN using Eurotubes) or Arm B (Standard PN using 2/3-chamber bags), or to Arm A-1 (low glucose using Eurotubes). Patients will be assessed (physical exam, ECOG, weight, QoL, lab tests, AEs, HPN documentation) every 4 weeks during the 12 months HPN treatment period. Co-primary endpoints are incidence of CRI and patient autonomy (rate of self-administered PN at home). Secondary endpoints comprise weight change, change in albumin and CRP levels, overall survival, QoL, and safety. Recruitment has just started; first patient in was on February 5th, 2020. Clinical trial information: NCT04105777 .
Glucocorticoids in the treatment of Kawasaki disease
Authors: 胡景伟, 周忠蜀
Journal: BMJ (2011)

川崎病是一种以全身中、小动脉炎性病变为主要病理特征的急性热性发疹性疾病,目前已取代风湿热成为儿童期后天性心脏病的主要病因[1].冠状动脉病变包括冠状动脉扩张和冠状动脉瘤形成,是川崎病最严重的并发症。