tbuckley/cabot-search huggingface dataset:
Prostate cancer biomarker enrichment and treatment selection (PC-BETS) study: A Canadian cancer trials group phase II umbrella trial for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Kim N. Chi, Som Mukherjee, Fred Saad, Eric Winquist, Michael Ong, Michael Paul Kolinsky, Adrian G. Sacher, Cristiano Ferrario, Muhammad Salim, Robyn Jane Macfarlane, Nayyer Iqbal, Sebastien J. Hotte, Matti Annala, Jelena Petrovic, Dongsheng Tu, Moira Katherine Rushton, Francisco Emilio Vera Badillo, Martin Smoragiewicz, Alexander William Wyatt
Journal: Journal of Clinical Oncology (2020)

5551 Background: Genomic characterization of mCRPC has identified commonly occurring alterations but also recurrently mutated genes at much lower frequencies. To efficiently evaluate anti-tumor activity of novel targeted therapies in mCRPC patients (pts) we initiated an umbrella trial using circulating tumour DNA (ctDNA) to enrich accrual for cancers with alterations that may predict response. Methods: mCRPC pts that have progressed after treatment with a next generation AR-pathway inhibitor (ARPI) were enrolled to this multi-center, multi-arm, 2-stage phase II trial. Plasma cell-free DNA was subjected to targeted sequencing and pts allocated to a treatment arm by a Tumor Board (TB) based on a priori criteria (biomarker positive, BM+) or by randomization if biomarker negative (BM-). Primary objective was to determine the clinical benefit rate (CBR: PSA decline ≥50% (PSA50), CR/PR, or stable disease ≥12 weeks). We report on 1st-stage activity of arms evaluating inhibitors of CDK4/6 (palbociclib), WEE1 kinase (adavosertib), cMET (savolitinib) and the AR inhibitor darolutamide. Additional planned arms include inhibitors of AKT (ipatasertib), Polo-like Kinase 4 (CFI-400945), immune checkpoints (durvalumab, tremelimumab) and carboplatin. Results: 250 pts were screened from two sequential trials over 29 months at 11 centers. Median time from blood draw to TB decision was 35 days. 169 pts (68%) had detectable ctDNA (≥1%) with a mean ctDNA fraction of 24% (range 1-95%). Commonly detected genomic alterations involved AR (49% gain, 24% mutation), TP53 (49%), PTEN/PI3K pathway (35%), DNA repair (23%: mismatch repair (5%), BRCA2 (8%), ATM (3%), CDK12 (5%), other (2%)) and CTNNB1/APC (14%). To date, 46 BM+ pts and 37 BM- patients were enrolled: median age 70 years (53-88), 100% had prior ARPI, 45% had prior docetaxel, 17% with visceral metastases. Accrual and CBR are presented in table. Adverse events were as expected. Conclusions: Prospective centralized screening of ctDNA to stratify mCRPC pts into a precision oncology trial is feasible. Activity was seen in 4 of 7 evaluable cohorts with darolutamide and adavosertib, meeting the threshold for expansion of these arms. Clinical trial information: NCT03385655, NCT02905318 . [Table: see text]
急性疼痛的现场判断和处理原则
Authors: 冯庚
Journal: BMJ (2004)

疼痛是因伤病造成的一种特殊的、主观的躯体痛苦感觉,是由体内外伤害性刺激引起的一种复杂的心理生物学过程.疼痛是患者就医时提出的最常见的主诉,是临床发生率最高的症状之一.疼痛涉及临床学科范围之广,病种牵扯身体范围之大,患者预后好坏差别之悬殊非其他症状能比。
Clinical implications of the <i>SETBP1</i> mutation in patients with primary myelodysplastic syndrome and its stability during disease progression
Authors: Hsin‐An Hou, Yuan‐Yeh Kuo, Jih‐Luh Tang, Wen‐Chien Chou, Ming Yao, Yan‐Jun Lai, Chien‐Chin Lin, Chien‐Yuan Chen, Chieh‐Yu Liu, Mei‐Hsuan Tseng, Chi‐Fei Huang, Ying‐Chieh Chiang, Fen‐Yu Lee, Ming‐Chih Liu, Chia‐Wen Liu, Shang‐Yi Huang, Bor‐Sheng Ko, Shang‐Ju Wu, Woei Tsay, Yao‐Chang Chen, Hwei‐Fang Tien
Journal: American Journal of Hematology (2013)

Mutations of the SET binding protein 1 ( SETBP1 ) gene have been identified in patients with myeloid neoplasms, but the clinical relevance of this mutation and its association with other gene mutations in myelodysplastic syndrome (MDS) and the stability during disease progression remains unclear. Mutations in SETBP1 gene at exon 4 were analyzed by polymerase chain reaction and direct sequencing in 430 MDS patients. The results were correlated with clinical features, cytogenetics, gene mutations and treatment outcomes. SETBP1 mutations were identified in 14 (3.3%) of the 430 patients with primary MDS based on the FAB classification and 8 (2.4%) of the 333 patients based on the WHO classification. The SETBP1 mutation was closely associated with higher white blood cell counts, isochromosome of 17q, monosomy 7, and mutations of ASXL1, EZH2 and SRSF2 . With a median follow‐up of 43.9 months, MDS patients, based on either the FAB or WHO classification, had a significantly poorer overall survival (OS) if they harbored SETBP1 mutation. Further, SETBP1 mutation was an independent poor prognostic factor for OS (HR = 1.842, CI 95%, 1.1018–3.332, P = 0.043) irrespective of age, sex, and the International Prognostic Scoring System. Sequential analysis showed that the original SETBP1 mutations in the eight SETBP1‐ mutated patients studied were retained while two of the 101 SETBP1 ‐wild patients acquired novel SETBP1 mutations during follow‐ups. The SETBP1 mutation is associated with poor prognosis in MDS. The mutation can be acquired during the clinical course suggesting it may play a role in disease progression. Am. J. Hematol. 89:181–186, 2014. © 2013 Wiley Periodicals, Inc.
Chronic disease management in community:challenge and strategy
Authors: Guang-zheng Xu, Hui-qin Zhang
Journal: BMJ (2008)

In a survey on chronic disease management in Xujiahui Community,we found that the general practice team was facing the following problems：①Heavy burden of follow-up work by a relatively smaller number of physicians;②Misunderstanding of health and insufficient recognition of the importance of chronic disease management among community residents;and③Delayed database construction and inefficient performance.In this study,we described the strategies to improve chronic disease management in communities.

Key words: 
Disease management;  Community health services
Assessment of PD-L1 expression in circulating tumor cells in patients with breast cancer.
Authors: Junqing Chen, Zhanhong Chen, Xiaojia Wang
Journal: Journal of Clinical Oncology (2020)

e13001 Background: Evidence is accumulating that the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced breast cancer patients. PD-L1 tumor expression is emerging as a potential biomarker in PD-1/PD-L1 checkpoint blockade therapies. However, PD-L1 expression on tumor tissue is limited by the temporal and spatial heterogeneity as well as insufficient tumor tissue samples. PD-L1 expression in circulating tumor cells (CTCs) might overcome the limitation. We investigated the utility of CTCs as a noninvasive method to evaluate PD-L1 status in breast cancer patients. Methods: 46 breast cancer patients including 42 metastatic breast cancer patients and four early breast cancer patients were enrolled. CTCs were collected from peripheral blood samples using a microfluidic-based CTC separator. A novel staining procedure which included fluorescent glucose analog staining and immunostaining targeting CD45, vimentin and PD-L1 were analyzed. PD-L1 expression level was analyzed as the fraction of PD-L1 positive CTCs among total CTCs. Results: 46 breast cancer patients all had detected CTCs, ranging from 12 to 110. The fraction of PD-L1 positive CTCs varied from 2.08% to 85.69%. PD-L1 expression was obviously higher in triple negative breast cancer (TNBC) patients as compared with non-TNBC patients (47.16% vs 26.23%, P &lt; 0.01). Interestingly, we observed that PD-L1 positive CTCs were also detected in four early TNBC patients. No significant association was found between PD-L1 expression and mesenchymal CTC phenotype. Conclusions: These data suggest that assessment of PD-L1 expression in CTCs from breast cancer patients is feasible. PD-L1 expression in CTCs might serve as a complementary tool for PD-L1 expression analysis in breast cancer patients.
Clinical analysis for 112 cases of cardiac neuro-functional disease in children
Authors: 闫宗荣, 吴明昌, 刘铁莲, 黄立新, 丁学勤
Journal: BMJ (2005)

目的 探讨儿童心脏神经功能性疾病的特点及与器质性心脏病的鉴别.方法对儿童以憋气、胸闷等症状就诊的心脏神经功能性疾病112例的临床资料进行回顾性分析.结果 112例均无心脏阳性体征,常规做X线胸透和(或)超声心动图、心电图、心向量图、心肌酶等检查,结果均正常者47例,其中心脏神经症35例、直立调节障碍12例.因心电图异常疑似心肌炎者65例,其中有ST-T改变的28例经心得安试验证实为β肾上腺素能受体功能亢进症;37例心电图示电轴左偏或疑似左前束支传导阻滞,后者经心向量图检查排除了左前束支传导阻滞,明确为电轴左偏.65例均排除了心肌炎.对住院的35例进行病因分析,显示其与社会、家庭、自身等因素有关.结论心脏神经功能性疾病应与心肌炎鉴别,治疗上应注意消除病因,心理治疗或辅以β受体阻滞剂可改善症状。
High negative pressure drainage in the treatment of neck lymphatic tuberculosis
Authors: Kui Hu, Kai Zhao, Qunya Tan
Journal: BMJ (2014)

To observe the clinical efficacy of high negative pressure drainage in the treatment of neck lymphatic tuberculosis. A retrospective study was conducted for 143 cases of neck lymphatic tuberculosis from June 2011 to September 2012. There were unilateral (n=91) and bilateral (n=52) cases. The types were nodular (n=27), infiltrating (n=39), abscess (n=47) and ulcer (n=30). All cases underwent debridement, regional lymphadenectomy and drainage with high negative pressure. There was no occurrence of prosopoplegia or accessory nerve injury. Two cases had lymphatic fistula. High negative pressure drainage has definite efficacies for neck lymphatic tuberculosis.


Key words: 
Tuberculosis, lymph node; Drainage, high negative pressure
Non-operative treatment for patients with acute uncomplicated appendicitis
Authors: Tong Tian, Xiaowei Wang, Haowei Lyu
Journal: BMJ (2016)

Total 786 cases of acute uncomplicated appendicitis(UCAA)were included for analysis. All the cases were given antibiotics as a main treatment. Clinical cure rate and the number of cases requiring surgery were observed. Patients with conservative treatment were followed up and the recurrence was observed. Logistic regression was applied to analyze the risk factors of recurrence. Among 786 cases, 774 (98.5%) were treated conservatively and achieved clinical cure; 68 cases (9.0%) had recurrence during follow-up, the median time to recurrence was 11 months (1-33 months). Logistic regression analysis showed that age(OR=1.124, 95%CI: 1.067-3.790, χ2=2.767, P=0.041)and appendix bezoar (OR=1.649, 95%CI: 1.281-4.055, χ2=3.935, P=0.027)were independent risk factors for recurrence. Non-operative treatment for acute uncomplicated appendicitis shows a good short and long term effects. Surgical excision may be a better choice for the patients with high risks of recurrence.


Key words: 
Appendicitis; Drug therapy; Recurrence
Developing and validating an approach for diagnosing and prognosticating cancer from biochemical motifs in T-cell receptors.
Authors: Jared L Ostmeyer, Lindsay G Cowell, Scott Christley
Journal: Journal of Clinical Oncology (2020)

e15260 Background: Immune repertoire deep sequencing allows profiling T-cell populations and enables novel approaches to diagnose and prognosticate cancer by identifying T-cell receptor sequence patterns associated with clinical phenotypes and outcomes. Methods: Our goal is to develop a method to diagnose and prognosticate cancer using sequenced T-cell receptors. To determine how to profile the specificity of a T-cell receptor, we analyze 3D X-ray crystallographic structures of T-cell receptors bound to antigen. We observe a contiguous strip typically 4 amino acid residues in length from the complimentary determining region 3 (CDR3) lying in direct contact with the antigen. Based on this observation, we extract 4 residue long snippets from every receptor’s CDR3 and represent each snippet using biochemical features encoded by its amino acid sequence. The biochemical features are combined with information about the abundance of the snippet or the receptor and scored using a machine learning based approach. Each predictive model is fitted and validated under the requirement that at least one positively labelled snippet appears per tumor and no positively labelled snippets appear in healthy tissue. Results: Using a patient-holdout cross-validation, we fit predictive models to distinguish: 1. colorectal tumors from healthy tissue matched controls with 93% accuracy, 2. breast tumors from healthy tissue matched controls with 94% accuracy, 3. ovarian tumors from non-cancer patient ovarian tissue with 95% accuracy (80% accuracy on a blinded follow-up cohort) 4. and regression of preneoplastic cervical lesions over 1 year in advance with 96% accuracy. Conclusions: Immune repertoires can be used to diagnose and prognosticate cancer.
Preclinical efficacy of humanized, non–FcγR-binding anti-CD3 antibodies in T-cell acute lymphoblastic leukemia
Authors: Christine Tran Quang, Benedetta Zaniboni, Romain Humeau, Etienne Lengliné, Marie Emilie Dourthe, Rajkumar Ganesan, Sanjaya Singh, Justin M. Scheer, Vahid Asnafi, Jacques Ghysdael
Journal: Blood (2020)
Attaching importance to identification and rescue of cardiac arrest at grassroots level
Authors: Yan Liang
Journal: BMJ (2019)

心脏骤停分为心室颤动、无脉搏室性心动过速、电机械分离和心脏停搏，是猝死的主要原因，严重威胁着我国居民的健康。由于其突发性和不可预知性，决定了心脏骤停的识别和救治应普及到所有基层医院医务人员、公共场所服务人员，甚至逐渐推广到全社会。立即进行有效的心肺复苏有助于最大效率地提高患者生存率。《心脏骤停基层诊疗指南（2019年）》的发表将在这一领域起到重要的推动作用。
Characterization of chemotherapy-induced peripheral neuropathy (CIPN) using patient-reported outcomes (PRO) and quantitative sensory testing (QST).
Authors: Ting Bao, Wanqing Iris Zhi, Connie Chen, Raymond E Baser, Qing Susan Li, Katherine Panageas, Steven Harte, Jun J. Mao
Journal: Journal of Clinical Oncology (2020)

e24078 Background: CIPN is a common, potentially debilitating, and dose-limiting side effect experienced by cancer survivors. CIPN encompasses symptoms such as pain, numbness, and tingling, which can be measured subjectively by PRO, or semi-objectively by QST; however, little is known about how QST measures differ among patients with and without CIPN, or if QST outcomes correlate with symptom profiles measured by PRO. Methods: CIPN is a common, potentially debilitating, and dose-limiting side effect experienced by cancer survivors. CIPN encompasses symptoms such as pain, numbness, and tingling, which can be measured subjectively by PRO, or semi-objectively by QST; however, little is known about how QST measures differ among patients with and without CIPN, or if QST outcomes correlate with symptom profiles measured by PRO. Results: 116 patients with CIPN and 10 control patients without CIPN were analyzed. NRS and FACT/GOG-Ntx scores were significantly worse in the CIPN group compared to controls (all p&lt; 0.001). The mean (Standard Deviation) TT for CIPN and control patients was 3.61 (0.43) and 3.38 (0.32), respectively (p = 0.059), in hands; and 3.86 (0.70) and 3.38 (0.56), respectively (p = 0.043), in feet. The mean VT was 6.06 (3.45) and 3.87 (1.01), respectively (p=0.032), in hands; and 19.14 (11.09) and 8.43 (3.22), respectively (p&lt;0.001), in feet. There was no significant difference in THT between groups. The correlation coefficients between PRO with QST measures in all patients are listed in the table below. Conclusions: Our study suggested that patients with CIPN have significantly worse symptoms and tactile and vibratory threshold measured by QST when compared with controls. Mild to moderate correlations were observed between PROs and QST, suggesting that CIPN symptoms severity correspond to sensory sensitivity. As CIPN presents a diverse range of symptoms, improved quantification of subjective and objective measures for CIPN can help the incorporation of these tools into future clinical trials. Clinical trial information: NCT03183037 and NCT03292328 . [Table: see text]
Clinical characteristics and angio-architecture features of dural arteriovenous fistulas
Authors: Jing-wei Li, Yun Luo, De-ning Guan, Chong Wang, Yu-jie Huang, Shi-jie Na
Journal: BMJ (2013)

To investigate the clinical characteristics and angio-architecture features of patients with dural arteriovenous fistulas (DAVF). The clinical data of 48 patients with DAVF were analyzed retrospectively. All patients were diagnosed by digital subtract angiography and 43 cases were also examined by MRI. Patients were divided into the bleeding group and non-bleeding group, whose clinical features and angio-architecture were compared. Of 48 cases, 13 patients demonstrated intracranial bleeding, and men were more common in bleeding group (M/F: 10/3) than in non-bleeding group (M/F: 15/20)(P=0.036). The Cognard scores of bleeding group and non-bleeding group were 3.77±0.28 and 2.49±0.21, respectively (P=0.002); however, there was no significant difference in age and the number of feeding artery between two groups. The results indicate that male patients with high Cognard scores tend to intracranial bleeding.


Key words: 
Arteriovenous fistulas; Angiography, digital subtraction
Feasibility of randomized controlled trials (RCTs) for drugs approved by the United States Food and Drug Administration (FDA) based on single arm studies.
Authors: Rebekah Rittberg, Piotr Czaykowski, Saroj Niraula
Journal: Journal of Clinical Oncology (2020)

e19115 Background: US FDA introduced an Accelerated Approval (AA) pathway in 1992 to expedite access to promising new drugs, based on the assumption that RCTs would delay introduction or prove unfeasible. One resulting trade-off is an “interim” compromise in acceptable level of evidence: such approvals have increasingly relied on Overall Response Rates (ORR) from Single Arm Studies (SAS). FDA requires confirmation of benefits for such drugs in future RCTs, but that requirement may take years and often never met. Methods: We pooled drugs approved by FDA over 5 years based on ORR observed in SASs for solid tumors. We calculated the differences in ORR between the newly approved drugs and existing standard of care for each cancer sub-type, and designed hypothetical RCTs necessary to detect that difference. RCTs were designed based on power of 0.80, α-error of 5% (two-sided), and 1:1 randomization, using PS software (Vanderbilt University). We estimated accrual time for the RCTs using disease incidence and annual death rates for each cancer subtype in USA using Surveillance, Epidemiology &amp; End Results records. Results: 28 of 129 (22%) FDA approved drugs for solid tumors, from 2015-2019, were based on SAS. Median sample size of 107 patients per approval (range 26-550). Drugs were approved based on median ORR of 38.9% (range 13-78%), compared to median ORR of 24.4% (range 5-62%) for existing standard of care [median difference in ORR 14.9% (range 6-45%)]. Using established statistical standards, median sample size required to conduct RCTs was 206 patients (range 44-1724); based on a conservative accrual rate of 5% of all eligible US patients, for 22 of 24 approvals RCTs with ORR as primary endpoint could have been completed within a timeframe equal to or less than the time used for undertaking the SAS. Drugs for 4 indications of 28 had a lower ORR compared to existing standard of care, while lacking evidence of superiority in any other survival outcome, raising important concerns about the approval process. Conclusions: Feasibility of conducting RCTs with an ORR endpoint within an acceptable time-frame does not appear to be a practical constraint for an overwhelming majority of drugs approved by FDA based on SAS alone. This finding questions the necessity of accepting a lower bar for efficacy and toxicity while approving drugs using the AA pathway, especially when supported by clinical equipoise with existing standards of care. ORR was lower than existing standard of care for 4 indications, putting rationale for these approvals into question.
Effects of lactated Ringer's solution on ischemic myocardium during optical coherence tomography
Authors: Jia-hong Xu, Ru-hui Liu, Yang Liu, Jin-fa Jiang
Journal: BMJ (2012)

The examinations of optical coherence tomography (OCT) images were obtained in 136 patients. Lactated Ringer's solution or physiological saline was used randomly as perfusate. Their electrocardiogram and cardiac enzymes were acquired to compare the safety and image quality of two perfusates.The incidence of ventricular arrhythmia and rise of cardiac enzymes were lower in the lactated Ringer's solution group than those in the physiological saline group.Yet the image quality of OCT had no difference.The use of lactated Ringer's solution as perfusate instead of physiological saline in OCT examination may protect the ischemic myocardium and reduce the incidence of complications.

Key words: 
Tomography,optical coherence;  Myocardium
红外偏振光星状神经节照射并调制中频电治疗颈性眩晕
Authors: 魏智钧, 欧阳颀, 肖宁, 李自立
Journal: BMJ (2010)

多数学者认为,颈源性眩晕主要是由椎-基底动脉供血不足及颈交感神经功能亢进所致.单纯神经节阻滞术治疗颈源性眩晕风险较高,对颈椎周围组织结构治疗作用较小.近两年来,我科使用红外偏振光星状神经节照射并中频电治疗颈源性眩晕患者,疗效肯定。
An implantable cardioverter defibrillator but not amiodarone reduced risk of death in congestive heart failure
Authors: Yu-guo Zhang, Hua Shi, Wen-wei Chen
Journal: BMJ (2006)

：Seventy eight patientssuspected of intrauterine adhesion (IUA) were scanned with two-dimensional (2D) andthree-dimensional (3D) transvaginal uhrasonography, the results were analyzed withhysteroscopic findings as the gold standard. The sensitivity, specificity, accuracy,positive predictive value and negative predictive value of three-dimensional transvaginalultrasonography in diagnosis of IUA were 97% (58/60), 18/18, 97% (76/78), 100% (58/58) and90% (18/20). Three-dimensional transvaginal ultrasonography was more accurate in diagnosisof IUA than two-dimensional ultrasonography ( P < 0. 01 ),and the IUA classificationand grading with three-dimensional transvaginal ultrasonography was better correlated withhysteroscopic findings.
Neoantigen-based vaccination as a practical measure for head and neck cancer treatment.
Authors: Xiao-bin Zheng, Chuan-ben Chen, Yu Chen, Shiguang Hao, Liu Jun, Jia-ni Xiong, Jin Lin, Yaping Xu, Yan-Fang Guan, Yi Li, Yingying Huang, Yuting Yi, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e18528 Background: The view that neoantigens serve as potential vaccine targets has arisen in the last decade. Clinical and computational efforts have been done to increase the practicality of its application in real world. With these advances, we conducted a retrospective study on a Chinese population to explore the clinical feasibility of neoantigen-based vaccines for head and neck cancer treatment. Methods: Tumor and normal samples were profiled using a 1021-gene panel. Sequencing data were pre-analyzed according to our in-house standard procedures. Class I HLA typing was completed using OptiType v1.0. Curated somatic mutations in coding regions (SNVs and non-frameshift Indels with an allele frequency ≥ 5%) were collected and altered peptides produced by these mutations were analyzed using NetMHCpan v4.0. Peptides with an IC 50 &lt; 500 nM were considered potential binders, and especially, those with an IC 50 &lt; 50 nM were considered strong binders. An altered peptide was considered a neoantigen if IC 50 altere d is &lt; IC 50 wildtype . Results: We analyzed a total of 243 patients and detected 114 unique HLA alleles. By carrier percentage, the top three alleles are C*01:02 (44%), B*46:01 (36%), and A*11:01 (33%). In total, 743 mutations were deemed eligible for neoantigen prediction and 223 unique neoantigens were found. Of these neoantigens, 67 (carried by 21% of patients) were strong binders, among which 26 (carried by 9% patients) exhibited a great fold change (≥ 5 folds) of binding affinity. Moreover, the neoantigens in these patients are unique, as only two neoantigens were shared. A search for shared neoantigens revealed a combination of mutation PIK3CA p.E542K and HLA A*11:01, which was detected in 0.54% of all patients. Additionally, 43.6% (106/243) of patients were diagnosed with nasopharyngeal carcinoma, among whom 42% (44/106) possessed predicted neoantigens, including 15 patients with strong-binder neoantigens. Conclusions: (1) Neoantigen-based vaccination is a practical measure to treat patients with head and neck cancer, as indicated by the percentage of patients harboring strong-binder neoantigens. (2) Off-the-shelf neoantigen vaccines may not be practical, given the result that the most common combination of a neoantigen-producing mutation and the corresponding HLA was only found in 0.54% of all patients.