tbuckley/cabot-search huggingface dataset:
IMpower150: Exploratory analysis of brain metastases development.
Authors: Federico Cappuzzo, Martin Reck, Mark A. Socinski, Tony S. K. Mok, Robert M. Jotte, Gene Grant Finley, Delvys Rodriguez-Abreu, Joachim Aerts, Howard West, Makoto Nishio, Liza C Villaruz, Shelly Coleman, Anthony Lee, Hans Kristian Vollan, Wei Yu, Roxana Ioana Sufan, Ilze Bara, Fabrice Barlesi
Journal: Journal of Clinical Oncology (2020)

9587 Background: In the global phase III IMpower150 study (NCT02366143), atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP] (ABCP) showed significant improvements in PFS and OS vs BCP in patients with chemotherapy-naive metastatic NSCLC (Socinski et al. N Engl J Med 2018). Because bev has been shown to delay or prevent brain metastases progression in NSCLC (Fu et al. J Chemother 2016; Ilhan-Mutlu et al. Mol Can Ther 2016), exploratory analyses were conducted to assess the development of brain metastases in patients treated with ABCP, BCP and atezo + CP (ACP) in IMpower150. Methods: A total of 1202 patients (intention-to-treat [ITT] population) were randomized 1:1:1 to receive ABCP, ACP or BCP. Doses were given every 3 weeks: atezo 1200 mg, bev 15 mg/kg, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m 2 . Co-primary endpoints were investigator-assessed PFS and OS in ITT–wild-type (no EGFR or ALK alterations) patients. Exploratory analyses included the rate and time to development (TTD) of new brain metastases in the ITT population, regardless of the presence of baseline brain metastases, as well as safety. Brain scans were performed as clinically indicated, and analyses were based on investigator assessments. Results: With a minimum follow-up of 32.4 months in the ITT population (data cutoff: September 13, 2019), 100 patients had developed brain metastases, with the highest rate of new brain lesions seen in the ACP (11.9%) vs the ABCP (7.0%) and BCP (6.0%) arms (table). Median TTD was not reached in any arm; a trend toward delayed TTD was seen in the ABCP vs BCP arm (HR, 0.68 [95% CI: 0.39, 1.19]). Among patients with and without brain metastases, 17 (35.4%) and 155 (44.0%) in the ACP arm, 18 (64.3%) and 207 (56.7%) in the ABCP arm and 10 (41.7%) and 183 (49.5%) in the BCP arm had Grade 3-4 treatment-related adverse events, respectively. Conclusions: The ACP arm had the highest rate of new brain lesions, whereas the ABCP and BCP arms had similar, lower rates. Taken together with the trend toward delayed development of new brain lesions with ABCP, the data suggest that adding atezo to BCP may not reduce the rate of new brain lesion development but may delay the time to new lesion development. No new safety signals were observed in this exploratory analysis. Clinical trial information: NCT02366143 . [Table: see text]
Association of pathogenic germline variant KDR Q472H with angiogenesis and resistance to treatment in melanoma.
Authors: Margaret Chou, Keith M. Giles, Irineu Illa-Bochaca, Justin Mastroianni, Eleazar Vega-Saenz de Miera, Michelle Krogsgaard, Iman Osman
Journal: Journal of Clinical Oncology (2020)

10060 Background: Preclinical data suggest that melanoma angiogenesis promotes resistance to MAPK-pathway (MAPKi) and immune checkpoint inhibitors (ICIs). However, phase II clinical trials of anti-angiogenic therapy in melanoma were disappointing. We previously identified a pathogenic germline variant Q472H in the kinase insert domain receptor [KDR Q472H; vascular endothelial growth factor receptor-2 (VEGFR-2)] in 35% of primary melanoma patients. We hypothesize that KDR Q472H promotes resistance to MAPKi or ICIs, and that combined MAPKi or ICI and VEGF pathway inhibition may improve outcomes in patients harboring the variant. Methods: Metastatic melanoma (MM) patient clinical data and biospecimens enrolled in the NYU Langone Medical Center Melanoma program were studied. KDR status was determined by TaqMan assays. Tumor microvessel density (MVD) was assessed by CD34 immunohistochemistry. The impact of KDR Q472H on the tumor microenvironment was determined by RNA-seq and Nanostring. Synergy between BRAF (dabrafenib) and VEGFR-2 (lenvatinib) inhibitors in KDR-genotyped MM cell lines was assessed using cell proliferation assays and the Chou-Talalay method. Synergy between ICIs and anti-VEGFR-2 was evaluated in vivo using a B16 melanoma model. Results: We studied 221 MM patients (38% KDR Q472H variants). KDR Q472H variant was significantly associated with higher tumor MVD (P = 0.002). Among the MAPKi-treated patients, KDR Q472H homozygotes had shorter median progression-free survival (PFS, 3.3 vs 9.7 months, P = 0.009) than KDR wild type (WT). In patients treated with anti-PD-1-based therapies, response rates were lower in KDR Q472H variant patients compared to WT (P = 0.012), with shorter median PFS (8.4 months vs not reached, P = 0.0443). Transcriptomic analyses identified an immunosuppressive phenotype in KDR Q472H tumors, with reduced expression of genes associated with chemotaxis, inflammation, T cell activity, and antigen presentation. Consistent with this finding, VEGFR-2 blockade in a KDR Q472H B16 mouse melanoma model augmented the anti-melanoma immune response. KDR Q472H cell lines displayed synergistic cytotoxicity with dabrafenib and lenvatinib, compared to KDR WT cells. Conclusions: Our data demonstrate that melanoma patients with pathogenic germline variant KDR Q472H may be more resistant to both ICIs and MAPKi. Anti-angiogenic therapy should be reconsidered within this specific subset of patients in prospective clinical trials.
Relative risk of HTN and major cardiovascular events associated with use of androgen receptor antagonists for nonmetastatic, castration-resistant prostate cancer.
Authors: Nusrat Jahan, Francis Mogollon-Duffo, Shabnam Rehman, Sakshi Singal, Fred L. Hardwicke
Journal: Journal of Clinical Oncology (2020)

e17605 Background: Metastatic, castration-resistant prostate cancer (mCRPC) is a lethal disease, often preceded by nonmetastatic, castration-resistant phase. Recently, three androgen receptor (AR) antagonists — apalutamide, enzalutamide, and darolutamide — have been approved for nonmetastatic, castration-resistant prostate cancer (nmCRPC). AR-antagonists have been associated with increased risk of hypertension (HTN) and major cardiovascular (CV) events. We conducted a systematic review and meta-analysis of the published phase 3 randomized controlled trials (RCTs) to determine the relative risk of HTN and major CV events associated with use of AR-antagonists for nmCRPC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts from inception until November 2019. Published phase 3 RCTs using AR-antagonists in the study arm for nmCRPC and reporting the number of events of HTN and major CV events were included in the analyses. We used Mantel-Haenszel (MH) method and random effects model to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I 2 value and Cochran’s Q-test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) randomizing 2687 patients in the AR-antagonist arms and 1417 patients in the control arms were included in the final analysis for HTN. SPARTAN did not include data for major CV events; hence, other two studies comprising 2903 patients were analyzed for major CV events. Major CV events included myocardial infraction/coronary artery disease, ischemic/hemorrhagic cerebrovascular events, and heart failure. AR-antagonists used in the study arms were — ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy. Randomization was 2:1 in all studies. The pooled RR of any-grade HTN is 1.5 (95% CI: 1.03 – 2.18, p = 0.03, I 2 = 70%); and, the pooled RR of grade ≥3 HTN is 1.39 (95% CI: 1.03 – 1.88, p = 0.03, I 2 = 13%). The pooled RR of any-grade major CV events is 1.49 (95% CI: 1.05 – 2.13, p = 0.03, I 2 = 0%); and, the pooled RR of grade ≥3 major CV events is 1.80 (95% CI: 1.11 – 2.92, p = 0.02, I 2 = 0%). Conclusions: Our meta-analysis demonstrated use of AR-antagonists for nmCRPC is associated with increased risk of HTN and major CV events. A careful selection of patients and aggressive management of the CV risk factors are crucial to enhance safety and proper utilization of these promising drugs.
Changes of somatosensory evoked potentials in endovascular embolization for cerebral arteriovenous malformation
Authors: 陈立一, 龙霄翱, 陈兵
Journal: BMJ (2007)

目的 探讨在脑动静脉畸形(AVM)介入栓塞治疗中躯体感觉诱发电位(SEP)的变化.方法 监测46例AVM患者在介入栓塞治疗中上肢正中神经SEP(N20)波形的变化,将N20波形变化与术中、术后神经功能障碍的变化对照分析.结果 在AVM介入栓塞过程中,40例患者术中SEP无明显变化,也无神经功能障碍,但其中1例术后出现对侧肢体肌力下降,对症治疗3 d后恢复正常;6例患者术中SEP出现异常,并有相应神经功能障碍,立即停止进一步手术操作并经导管内注射罂粟碱后,4例患者神经系统症状和体征明显改善,此时SEP变化均低于异常标准,术后未发现有神经功能障碍;另2例SEP异常未得到改善,术中、术后神经功能障碍也无改善.结论 SEP对脑缺血的监测有高度敏感性和特异性,有助于预防和减少AVM介入栓塞并发症的发生。
Application of neo-bioscore to a real-world cohort: Potential implications for patient selection, for escalation, and de-escalation of therapy.
Authors: Christine E. Simmons, Kaylie Willems, Stephen K. L. Chia, Megan Tesch, Kaitlyn Kespe, Nathalie LeVasseur
Journal: Journal of Clinical Oncology (2020)

e19094 Background: Recent studies have demonstrated that escalation of therapy for patients with residual disease after neoadjuvant therapy for breast cancer may result in better long-term outcomes. However, refining patient selection based on prognosis has not been widely adopted. The Neo-Bioscore is a validated independent prognostic tool that can be readily applied clinically. The utility of this tool to predict the expected magnitude of benefit from escalation of therapy for ER+, HER2+ and TNBC disease has not yet been explored. Methods: A retrospective review of prospectively collected data from May 2012-May 2019 of patients treated with neoadjuvant chemotherapy followed by surgery was undertaken. The Neo-Bioscore was calculated for each patient. Kaplan-Meier method was used to generate disease-specific survival (DSS) curves, and 5-year DSS rates were estimated. These estimates were compared to those predicted by the original validation cohort. The potential benefit of further adjuvant therapy was extrapolated from data available in the published literature. Results: A total of 471 patients were included in this study; all were women, and the median age was 56 (range 24-88). 324 had residual disease at the time of surgery (68%). Median follow up from diagnosis was 4.4 years. 5-year DSS for each Neo-Bioscore category is seen in the Table below. This correlated with the predicted DSS with a correlation coefficient of X. For patients with residual disease, utilization of adjuvant capecitabine for those with ER+ or TNBC and utilization of adjuvant TDM-1 for those with Her2+ disease would have minimal impact on DSS in those with Neo-Bioscore of 0-2, modest benefit for those with Neo-Bioscore of 3-4, and would be of high benefit for those with Neo-Bioscore of 5 or higher. Conclusions: Neo-Bioscore is a tool that can be readily applied to a real-world cohort without additional pathological information, with good correlation to the predicted outcomes in validation studies. The impact and utility of the Neo-Bioscore to stratify patients for selection of adjuvant therapy will need to be validated, but may help better inform treatment in resource constrained environments. [Table: see text]
是肿瘤转移还是炎症扩散
Authors: 曾昭耆
Journal: BMJ (2006)

一位68岁的女患者,因突发寒战、高热(体温40 ℃)3 h,伴右腿肿及散在红斑,于1998年9月29日急诊入院. 患者12年前因左侧卵巢癌行妇科根治性切除手术(切除双侧卵巢、子宫、输卵管、大网膜),病理诊断为左侧卵巢黏液囊性低分化癌.化疗3年后,再次行剖腹探查并行腹腔淋巴结彻底清扫术.其后出现右下肢及下腹淋巴肿胀,并发生过几次类似病症。
Incidence trend of female urinary incontinence and its social impact
Authors: 朱兰
Journal: BMJ (2005)

女性尿失禁(female urinary incontinence)这一非致命性疾病,自20世纪90年代中期开始被认为是影响人类的五大疾病之一. 由于妇女们通常认为尿失禁是一种随年龄增长而出现的正常现象,全球范围内仅有8%的尿失禁妇女就诊,普遍存在就诊延迟现象. 加强临床医生对该病的重视并向民众普及相关知识已成为全球性问题。
MELAS mitochondrial myopathy: report of two cases and literature review
Authors: Haijuan Luo, Xiaowen Ye, Yue Ti, Xintian Wang, Yiyun Cheng
Journal: BMJ (2018)

Two male patients aged 33 and 38 years with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes(MELAS)admitted in our hospital in 2016 and 2017 were reported. The main symptoms included abdominal pain and distension, numbness and weakness of the limbs. MRI showed mild ventriculomegaly with deepened sulcus and widened cerebral fissure, deepened bilateral cerebellar sulcus and the widened cleavage, atrophy of cerebellum and brainstem, and manifestations of acute cerebral infarction. Gene analysis showed mutation of mitochondrial DNA(mtDNA)A3243G. After definite diagnosis was made, patients reveived coenzyme Q10, ATP and vitamin supplements for improving circulation, and neurotrophic drugs for symptomatic treatment. The symptoms were slightly improved after treatment and two cases were followed-up as outpatients.


Key words: 
MELAS syndrome; Gene diagnosis; Magnetic resonance imaging
Prognostic value of radiological extranodal extension detected by computed tomography for predicting outcomes in head and neck squamous cell cancer patients treated with radical chemoradiotherapy.
Authors: Abhishek Mahajan, Ankur Chand, Vijay Maruti Patil, Vanita Noronha, Amit Joshi, Nilesh Sable, Ankita Ahuja, Nandini Sharrel Menon, Jaiprakash Agarwal, Sarbani Ghosh Laskar, Anil D'Cruz, Pankaj Chaturvedi, D. Chaukar, P. S. Pai, Gouri Pantvaidya, Shivakumar Thiagarajan, Richa Vaish, Swapnil Rane, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

6560 Background: As per the AJCC 8th edition ENE/ECS is the most important predictor for N staging of HNSCC and is one of the key predictor of outcomes. Because ENE/ECS is based on pathological findings after surgery and it is difficult to predict outcomes for locally advanced squamous head and neck cancer (LASHNC) treated radically with CCRT. We hypothesized that ENE assessed by CT imaging (rENE) may directly correlate with outcomes in LASHNC treated radically with CCRT. Methods: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with LASHNC who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m 2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT). 536 patients were accrued,182 were excluded due to non-availability DICOM CT scan, 354 patients were analysed for rENE (based on 6 criterion for metastasis and 3 for rENE). Near equal distribution of patients was achieved in CRT arm (170 patients) and NCRT arm (184 patients). There were 181 (51.1%) oropharynx and 173(48.9%) larynx and hypopharynx patients. We evaluated association of radiological ENE and clinical outcomes.The endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). Results: There were 244(68.9%) patients with radiologically metastatic nodes, out of which 140(57.3%) had rENE. There was no significant association between rENE and CRT (p value 0.3) or NCRT (p value 0.412). The median follow-up was 33.0 months (95%CI 30.7-35.2 months). Complete response was achieved in 204 (57.6%) cases, PR/SD in 126(35.6%) cases and PD in 24(6.8%) cases. rENE positive patients had poor overall 3-year survival (46.7%), poor DFS (48.8%) and LRC (39.9%) than rENE negative cases (63.6%, 87%, 60.4%). rENE positive cases had 1.71 times increase chances of incomplete response than rENE negative cases. Overall stage, clinical positive node, response, rENE and site were the only significant factors for predicting OS, DFS and LRC. Conclusions: In conclusion, pre-treatment rENE can be regarded as an independent prognostic factor for survival (OS, DFS, LRC) in patients with LASHNC treated radically with CCRT. Pre-treatment rENE is not only associated with CCRT response but is also associated with poor prognosis and hence rENE, as an imaging biomarker, can stratify responder’s vs non-responders. Clinical trial information: CTRI/2014/09/004980 .
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric adenocarcinoma: A phase II clinical trial.
Authors: Yan Song, Ning Li, Lan Mu, Shu Zhang, Qingxia Fan, Xinjun Liang, Xianli Yin, Zhixiang Zhuang, Yunpeng Liu, Jingdong Zhang, Xiaoge Kou, Haijun Zhong, Jing Huang
Journal: Journal of Clinical Oncology (2020)

4524 Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We investigated HX008, an Anti-PD1 Antibody, with irinotecan in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and/or fluoropyrimidine. Methods: This study is a multicenter, open, phase II clinical study of recombinant humanized anti-pd-1 monoclonal antibody HX008 injection plus Irinotecan that was conducted at 11 hospitals in China. Eligible patients are adults with histologically confirmed advanced gastric or gastro-oesophageal junction cancer. Subjects participating in this study are required to submit a archived tumor tissue specimen or newly obtained biopsy of tumor lesions at the site of no previous radiotherapy and peripheral blood (2mL) for detection of PD-L1 and MSI/MMR expression. The samples will be tested for expression of PD-L1 and MMR by immunohistochemistry (IHC) in the central laboratory, and MSI levels will be determined by polymerase chain reaction (PCR) and gel electrophoresis. Subjects received PD-1 monoclonal antibody HX008 at 200mg (d1, intravenous drip, once every 3 weeks) plus irinotecan at 160mg/m2 (d1, intravenous drip, 60 ~ 120min, once every 2 weeks). Response was assessed every 6 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Primary endpoints was objective remission rate (ORR). Results: Between October 2018 and September 2019, a total of 58 patients with advanced gastric or gastro-oesophageal junction cancer were enrolled in this study. Median (range) age was 61 (27-71) years, and most patients were male (72.4%). Among 53 patients who were evaluated, 15 (28.3%) experienced objective response and 22 (41.5%) experienced stable disease (SD). The median progression free survival (PFS) was 5.4 months, the one-year survival rate was 71.3%. The most common treatment-related adverse events of grade 3 or 4 included neutropenia(31.0%), anemia(15.5%), loss of appetite (6.9%), vomiting(5.2%), nausea(3.4%), diarrhea (1.7%) and fatigue (1.7%). There were no treatment-related deaths. Conclusions: HX008 injection plus Irinotecan demonstrated promising activity and manageable safety in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Clinical trial information: NCT03704246 .
Clinical analysis of 62 cases of children with dilated cardiomyopathy
Authors: Yan-yan Han, Su Nie, Jing-hui Sun, Shu-bo Zhai
Journal: BMJ (2009)

Clinical data of 62 children with dilated cardiomyopathy (DCM)admitted to hospital from January 1998 to December 2008 were retrospectively analyzed. The age of patients was from 14 months to 14 year with the average of 8. 2 years. Respiratory infection was the main triggering factor. Cardiac dilatation was the basic conditions for diagnosis of DCM. Arrhythmia was characteristic for DCM, and color cardio uhrasonography was an important procedure of diagnosis and evaluation for cardiomyopathy. With the integrated treatment 38 cases were discharged with improvement ( 61% ), 11 cases died ( 18% ). Early diagnosis and integrated treatment are critical for management of cardiomyopathy in children.

Key words: 
Cardiomyopathy;  dilated;  Child
关于社区首诊制的一些思考
Authors: 吴春容
Journal: BMJ (2007)

自从今年2月份卫生部推出社区首诊制之后,全国各地都在积极试行.社区首诊制似乎已经成为医疗体制改革和解决老百姓看病难问题的重要举措.在国家基本医疗保险体系的经济杠杆调控下,采取全科医生与社区居民双向选择登记注册,由社区全科医生首诊,与综合医院形成资源共享及分工合作的双向转诊制度是很多国家为老百姓提供基本医疗服务的主要途径,社区全科医生首诊只是其中的一个制度要求。
Establishment of assessment system for comprehensive clinical competency of general practice residents
Authors: Juan Shou, Shan-zhu Zhu, Xiang-jie Zhang
Journal: BMJ (2013)

Objective
To establish a assessment system for comprehensive clinical competency of general practice residents.


Methods
An assessment system for comprehensive clinical competency of general practice residents was developed with modified Delphi expert consultation during November 2010 to October 2011. Thirty three experts in clinical practice, education and administration of general practice were invited for two-round Delphi questionnaire consultation.


Results
In two-round consultation, the expert activity coefficient was 100%, the authority coefficient was 0.852 and 0.855, and the coordination coefficient for the importance of the indicators was 0.228 and 0.245 respectively (P=0.000). The opinions among the experts became consistent from round 1 to round 2. An assessment system was established, which consisted of 5 first-level (professionalism, communicate skills, clinical competency and professional development ability) and 36 second-level indicators.


Conclusion
The index system established in this study may be used as references for evaluating comprehensive clinical abilities of general practitioners systematically and objectively.


Key words: 
Educational measurement; Delphi technique; General practitioners
Association between central and peripheral circulating tumor cell (CTC) clusters in oral squamous cell carcinoma (OSCC): A prospective, observational study.
Authors: Ritvi K Bagadia, Vishal Uchila Shishir Rao, Ajay Balakrishnan, Abhijith George, Prashant Kumar
Journal: Journal of Clinical Oncology (2020)

e15548 Background: Around 90% of cancer-related mortalities are caused by tumor metastasis. CTC clusters, which constitute an intermediate stage of metastasis, have not been studied extensively in head &amp; neck cancers. The mortality rate of oral cancers remains alarmingly high, despite multimodality treatment. The aim of the study is to identify the presence of CTC clusters in patients with Oral Squamous Cell Carcinoma (OSCC) and to correlate their presence with clinical and pathological factors. Methods: Fifty patients diagnosed with histologically proven OSCC, treatment naïve, and underwent surgery at HCG Cancer Centre, Bangalore, were consented and enrolled in the study. An IRB-approved protocol allowed for the collection of 10 ml of blood from central (jugular) and peripheral veins intra-operatively, prior to tumor removal. The culturing of CTC clusters was done using ellipsoidal microwell plates maintained at hypoxic conditions, at the Institute of Bioinformatics, Bangalore. After fourteen days of culturing, the cells were fixed and stained for DAPI, Pan-CK and CD45. The CTC clusters were classified into Loose, Tight and very Tight based on the median gray values obtained from DAPI staining on ImageJ software. Clinical data was collected from patient records and subjected to analysis using Descriptive statistics. Results: From the 50 patients included in the study, 22 (44%) patients exhibited tight clusters in central blood, while only 13 (26%) patients exhibited tight clusters in peripheral blood. A higher clinical stage was observed in a greater percentage of patients with tight clusters in central blood (early: 45.5% versus late: 54.5%), but the same findings could not be inferred with pathological staging (early stage: 59.1% versus late stage: 40.1%). No significant correlation with adverse pathological features was noted. Conclusions: This observational study provides an insight into the varying biological behaviours of similarly grouped cancers, which is based on the standard TNM staging. The study forms the basis for the hypothesis of tight clusters in the central and peripheral circulation, correlating with loco-regional and distant metastasis respectively, thus leading to poorer disease-free and overall survival rates.