tbuckley/cabot-search huggingface dataset:
Intratumoural (IT) evolutionary landscape of high-risk prostate cancer and outcome: The PROGENY (PROstate cancer GENomic heterogeneitY) study of genomic and immune parameters.
Authors: Anuradha Jayaram, Gerald Goh, Bihani Yoshana Kularatne, Jasmin Waterhouse, Yaalini Shanmugabavan, Andrew Rowan, Yien Ning Sophia Wong, Alex Freeman, Ayse Akarca, Javier Herrero, Rachel Rosenthal, Nicholas McGranahan, Michelle Hung, Mark Emberton, Gerhardt Attard, Sergio A. Quezada, Teresa Marafioti, Hashim Uddin Ahmed, Charles Swanton, Mark David Linch
Journal: Journal of Clinical Oncology (2020)

e17500 Background: IT heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease and patient outcomes are uncertain. Methods: This was a prospective, single-arm, translational study using targeted multi-region prostate biopsies to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. A pre-defined exploratory objective was to evaluate the association of ITH, median inflammatory infiltrate (MII), total, clonal and neoantigens, with overall survival (OS) and time-to-next-line of therapy (TTNL). Results: 49 men with elevated prostate-specific antigen (PSA) and multiparametric-magnetic resonance imaging (MRI) detected PC underwent image-guided multiregion transperineal biopsy. 79 tumour regions from 25 patients (pts) with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. The median follow-up was 60 months (m) with 10 death events. For %ITH, MII, total, clonal and subclonal neoantigens, patients were split by the median. Conclusions: The PROGENY study provides a diagnostic platform suitable for studying tumour ITH and has the potential to identify poor outcome subgroups in PC. Larger sample numbers in prospective trials are warranted to further investigate this hypothesis. [Table: see text]
Survey on mental health status of rural-to-urban migrant workers in Shanghai
Authors: Tianhao Wang, Zhigang Pan, Yumiao Wu, Hua Yang, Yao Liu, Jian Gong, Wei Dai, Jing Zhou, Yao Shen
Journal: BMJ (2014)

Objective
To survey the mental health status of rural-to-urban migrant workers in Shanghai.


Methods
The survey subjects were selected from migrant workers in Shanghai with a multi-stage stratified cluster sampling method. The Symptom Check List(SCL-90 )scores were used for evaluation of metal health status.


Results
The prevalence of mental health problem of 5 626 rural-to-urban migrant workers in Shanghai was 18.8% (1 058/5 626). The mean total score of SCL-90 was 114.86±31.21. Compulsive-obsessive, interpersonal sensitivity, hostility ranked the top three among 9 factors, with scores of 1.37±0.43, 1.31±0.43 and 1.30±0.41 respectively. The mean total scores and scores of 9 factors of rural-to-urban migrant workers in Shanghai were lower than those of Chinese adults norm the mean total scores(129.96±38.76) (t=-15.34, -3.84--24.08 respectively, all P<0.01). There were significant differences in mental health among migrant workers with different age, education, marital status, living conditions and occupation(all P<0.05).


Conclusion
The prevalence of mental health problems in Shanghai rural-to-urban migrant workers is high, with are related to their age, education, marital status, living conditions and occupation.


Key words: 
Migrant worker; Mental health; Questionnaires; Cross-sectional studies
Empirical treatment of chronic cough
Authors: 黄漾, 魏为利, 邱忠民
Journal: BMJ (2009)

慢性咳嗽是指以咳嗽为惟一或主要症状,持续8周以上且胸片未见明显异常者,在不吸烟的成年人群中发病率高达10%～40%.长期持续咳嗽不仅损害身体脏器机能,还对患者的心理和社会功能造成负面影响,降低生存质量.如何及时有效地控制咳嗽症状,解除患者痛苦是临床医师常要面对的困难问题.病因导向治疗是提高慢性咳嗽治疗成功率的关键措施,也是慢性咳嗽诊治流程的基础;而经验性治疗作为慢性咳嗽诊治的补充手段,近年来也受到重视,在国内外颁布的咳嗽诊治指南中也占有一席之地,现介绍如下。
Final results from the phase I study expansion cohort of the selective FGFR inhibitor Debio 1,347 in patients with solid tumors harboring an FGFR gene fusion.
Authors: James M. Cleary, Gopa Iyer, Do-Youn Oh, Ingo K. Mellinghoff, Lipika Goyal, Matthew C.H. Ng, Funda Meric-Bernstam, Ignacio Matos, Tsu-Yi Chao, Rafik Ait Sarkouh, Kira Cretegny, Valerie Nicolas-Metral, Anna Pokorska-Bocci, Anne Vaslin, Claudio Zanna, Angela Zubel, Josep Tabernero, Keith Flaherty, David Michael Hyman
Journal: Journal of Clinical Oncology (2020)

3603 Background: Debio 1347 is a selective oral inhibitor of FGFR 1-3 tyrosine kinases. It exhibited high antitumor activity in in vitro and in vivo tumor models with FGFR1-3 gene fusions. Here we report the results of the expansion portion of a Phase 1 study of advanced solid tumors patients (pts) harboring an FGFR1-3 gene fusion. Methods: Pts with advanced refractory solid tumors harboring an FGFR1-3 gene fusion were enrolled. Based on results from the dose escalation portion, pts received Debio1347 80 mg once daily (qd) in 28-day cycles. Pharmacokinetics (PK) and pharmacodynamics were evaluated. The data cut-off was October 8, 2019. Results: Among 18 pts enrolled, 5 had primary brain tumors (PBT), 5 had cholangiocarcinoma, 2 had urothelial cancer, 2 had colon cancer, 1 patient each lung neoplasm, gastric cancer, endometrial cancer and squamous cell carcinoma of the chest wall. Tumors harbored fusions with FGFR1 (n = 1), FGFR2 (n = 8), and FGFR3 (n = 9). All had prior systemic therapy (median 3 lines; range 1-4). The most common treatment emergent adverse events were fatigue (50%), hyperphosphatemia (44.4%), anemia (38.9%), alopecia (33.3%), nausea (33.3%), vomiting (33.3%), constipation (33.3%), and palmar-plantar erythrodysesthesia syndrome (22.2%). Blurred vision was reported in 1 pt. There were no findings on ocular exams compatible with retinal detachment. No grade 3 AE related to study drug were reported. One patient needed dose reduction due to grade 2 nails toxicity. In PK analysis, plasma steady-state was rapidly achieved and serum phosphate increase correlated with Debio 1347 plasma exposure, confirming target engagement at 80 mg qd. Median follow-up was 18 weeks. Partial responses were observed in 3 pts harboring an FGFR2 fusion: 1 out of 2 colon cancer and 2 out 5 cholangiocarcinoma. Median duration of response was 16.1 weeks (range: 8.4-22.8+). Overall disease control was observed in 11 out of 14 pts without PBT (79%). Median PFS was 18.3 weeks. No signs of activity were observed in the 5 patients with PBT, all with an FGFR3-TACC3 fusion. Conclusions: Debio 1347 at the recommended dose of 80 mg qd was generally well tolerated and showed signs of activity in solid tumors harboring an FGFR fusion. The FUZE phase 2 clinical trial of Debio 1347 is recruiting FGFR fusion-positive advanced solid tumors irrespectively of tumor histology, excluding PBT. Clinical trial information: NCT01948297 .
空巢老人健康状况和社区卫生服务需求调查分析
Authors: 代爱英, 顾湲, 曹杰
Journal: BMJ (2004)

我们对北京苏州社区卫生服务站辖区内空巢老人的健康状况,及其对社区卫生服务的需求意愿进行摸底调查.空巢老人入组标准是:年龄大于60岁,没有子女或与其子女分开居住1年以上的居民.调查结果如下。
Evaluation of the quality-of-life (QOL) and socio-demographic characteristics of patients with leukemia and lymphoma: Comparison with sibling and control group.
Authors: Nurdan Tacyildiz, Tugba Karakose, Emel Cabi Unal, Handan Dincaslan, Gulsah Tanyildiz, Hatice Mine Çakmak
Journal: Journal of Clinical Oncology (2020)

e22524 Background: Pediatric cancer patients have increased survival rates with intensive and effective treatment methods which causing some chronic health problems and lower quality of life in long term follow up. In our study, patients in their active treatment period compared to patients who have completed their treatment in recent 5 years and more than 5 years groups, besides compared with their own siblings and healthy control group,evaluated in terms of quality of life ( QOL). Methods: This study has been daone in the Department of Pediatric Hematology-Oncology, Ankara University School of Medicine. A total of 191 children were included in the study, including 36 sibling, 76 children with leukemia (n:31) and lymphoma (n:45) besides 79 healthy children. The Turkish translation of the PedsQL questionnaire was used to evaluate the patients' quality of life. IBM SPSS-25 package program was used for statistical analysis. Results: When the sociodemographic characteristics of the patient, sibling and control group were examined; we determined that the patients, siblings and control groups were similar in age, age and gender. However, we found that the education level for the patient group was statisticaly signicantly lower then the siblings and the control group. In addition, physical and mental functionning and friendship capasity scores were lower in patient group than the other two groups. According to timing of the treatment; patients and parents quality of life scores were significantly lower than the patients that finished their treatment in recent 5 years or more than 5 years. QOL scores were higest in survivors and parents group that were in more than 5 years after completed the treatment. The risk of lower QOL in patients under treatment was 7.48 times higher than the children who had ≥5 years of treatment (OR = 7,48; p &lt; 0,05), and 2.64 times higher than those who were treated &lt; 5 years (OR = 2,64; p &gt; 0,05). In this study, there were no independent variables that had an impact on QOL of the sibling group. Conclusions: The QOLof patients diagnosed with leukemia and lymphoma is significantly lower than siblings and healthy group. No statistically significant difference was found between the sibling group and the healthy control group. After the end of active treatment, the QOL of the patients was reflecting important increase by the time .
Adverse reactions of captopril
Authors: 刘迎梅, 丁学兵, 巩延丽, 王涛, 陈晨, 宗兆凯
Journal: BMJ (2005)

卡托普利(captopril, 巯甲丙脯酸,开搏通)是人工合成的非肽类化合物,含有巯基,经过肾脏排泄,是较强的血管紧张素转换酶抑制剂,临床适用于各型高血压患者,还可以治疗充血性心力衰竭.由于开搏通的广泛应用,其副作用也越来越多地被临床医师所重视.现据国内文献报道作一总结。
肠易激综合征诊断和治疗的共识意见(2007,长沙)
Authors: 中华医学会消化病学分会胃肠动力学组
Journal: BMJ (2008)

肠易激综合征(irritable bowel syndrome,IBS)是一种常见的功能性肠病,以腹痛或腹部不适为主要症状,排便后可改善,常伴有排便习惯改变,缺乏可解释症状的形态学和生化学异常.世界各地流行病学研究报道显爪IBS是一种世界范围内的多发病。
Plasma ctDNA sequencing supplementary to tissue-based molecular profiling as a source of additional actionable information in advanced cancers.
Authors: Bradley Allen Hancock, Swee Seong Wong, Saloni Sinha, Tom Barber, Benjamin A. Salisbury, Steven M. Bray, Lori A. Smallwood, Bryan P. Schneider, Milan Radovich
Journal: Journal of Clinical Oncology (2020)

e15554 Background: The standard for tumor molecular profiling in precision oncology is the tissue-based biopsy. However, tissue biopsies are limited in the ability to capture the bulk of heterogeneity in advanced cancers. The integration of liquid biopsy diagnostics complementary to tissue-based sequencing may provide a broader perspective of heterogeneity and actionability. Methods: Patients with metastatic solid tumors were evaluated in the Indiana University Health Precision Genomics (PG) Program. We retrospectively analyzed existing genomic data from matched plasma and tissue that were collected within a 90-day window. Plasma sequencing was generated with a CLIA-certified test: FoundationACT/FoundationLiquid. Tumor tissue sequencing was performed either with CLIA-grade whole exome or a gene-panel. All sequencing data was reviewed by a molecular tumor board for the determination of a personalized treatment strategy. Molecular data for this analysis was concatenated and analyzed for mutations present in ctDNA but absent in tissue. Clinical actionability was defined based on clinical evidence of a biomarker to guide therapy or match a patient to a clinical trial. Results: 288 subjects with tissue- and plasma-derived mutation data were analyzed. Discordance, defined by the presence of a somatic mutation in the plasma that was not present in the tumor tissue, was detected in 156/288 (54%) of pairs. Interestingly, the discordance was clinically actionable in 26/288 (9%) subjects. In the 32 gene-level instances of actionable discordance, the 3 top mutated genes were PIK3CA (7), PTEN (4), and EGFR (4). Discordant mutations in ATM and CHEK2, which are actionable with PARP inhibitors, but also frequently mutated in clonal hematopoiesis of indeterminant potential (CHIP) represented 4/26 (15%) instances. A complete and formal CHIP analysis is ongoing. As a result of plasma discordance, targeted interventions were employed in 3/26 (12%) subjects targeting high TMB with immunotherapy, an ERBB2 mutation with ado-trastuzumab emtansine, and a BRCA1 mutation with olaparib. All 3 patients were non-responders. Conclusions: Discordant mutations that appear in ctDNA but not in matched tumor tissue is a common occurrence. The majority of these mutations are either not druggable or variants of unknown significance, but a significant subset would be deemed clinically actionable. Clinical efficacy of targeted intervention based on actionable liquid biopsy discordance warrants further investigation.
潜水员骨代谢生化指标的调查分析
Authors: 于青琳
Journal: BMJ (2005)

检测73名男性海军潜水员骨代谢生化指标血清钙、磷、碱性磷酸酶、骨钙素,尿钙与肌酐比值,尿Ⅰ型胶原交联氨基末端肽,骨密度.结果表明,潜水员组血清钙、磷、碱性磷酸酶水平与对照组比较差异无统计学意义(P>0.05);血清骨钙素水平和骨密度高于对照组(P<0.01);尿钙与肌酐比值和尿Ⅰ型胶原交联氨基末端肽水平低于对照组(P<0.01)。
Through left subclavian vein emergent cardiac pacing guided by "three-peint measurement" method
Authors: Hui Ren, Jun-kang Zhang, Jie Gong, Bo Yuan, Hai Lu, Lan-yan Qu
Journal: BMJ (2009)

Seventy eight patients who need bedside temporary cardiac pacing through left subclavian vein were divided into 2 groups. In group A (n=40) the three-point measurement method was applied: a was set for puncture point of left subclavian vein, b was the middle point of angulus sterni, c was the right edge of the sternum at the 4th intercostal space, the length of ab + bc was used to estimate the depth of right atrium for electrode to reach until the success of right ventricular pacing. In group B (n=38) the puncture to the right or the left subclavian vein for temporary pacing was performed with X-ray guidance in catheter lab. Total rescuing time, procedure time and the threshold voltage of cardiac pacing was recorded in each groups. All cases were successful paced without complication related emergency cardiac pacing with a successful rate of 100% in both groups. There was not difference between two groups in the procedure time and the threshold voltage of cardiac pacing (P > 0. 05). The total rescuing time of A group was (10.0± 2.2) min, and that of B group was (30.5±3.5) min (P<0.01). The average depth of the electrode was ab + bc +9.0 cm. The results suggest that three-point measurement method is valuable in the guiding of bedside emergent cardiac pacing through the left subclavian vein.

Key words: 
Cardiac pacing, artificial;  Therapy
儿童保健中的预见性指导
Authors: 周仲华, Kenneth Walker Rudd, 金世红
Journal: BMJ (2011)

儿童保健涉及的内容包括儿童的体格生长和社会心理发育、儿童营养、儿童健康促进和儿科疾病的预防及管理,目的是通过有效措施,促进有利因素,防止不利因素,保障儿童健康成长[1].2009年底卫生部下发了 ,明确了儿童保健在我国卫生工作中的重要位置.儿童保健系统管理工作目前在全国不少地方已经开展。
RESILIENT part I, an open-label, safety run-in of liposomal irinotecan in adults with small cell lung cancer (SCLC) who have progressed with platinum-based first-line (1L) therapy: Subgroup analyses by platinum sensitivity.
Authors: David R. Spigel, Luis G. Paz-Ares, Yuanbin Chen, Maria Jove, Oscar Juan-Vidal, Patricia Rich, Theresa M. Hayes, M Vanesa Gutierrez Calderon, Reyes Bernabe Caro, Alejandro Navarro, Afshin Dowlati, Bin Zhang, Yan Moore, Haofei Tiffany Wang, Jaba Kokhreidze, Natalya Nazarenko, Santiago Ponce Aix, Paul Bunn
Journal: Journal of Clinical Oncology (2020)

9069 Background: Most patients with extensive SCLC develop drug resistance to platinum-based 1L therapy or discontinue for other reasons, and second-line (2L) therapies are limited. RESILIENT (NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of 2L liposomal irinotecan monotherapy in adults with SCLC who progressed with platinum-based 1L therapy. Preliminary data from RESILIENT part 1 (cut-off May 8 2019; ≥ 12 weeks follow-up) showed that liposomal irinotecan 70 mg/m 2 free base every 2 weeks was generally well tolerated and had encouraging antitumor activity (Paz-Ares et al. WCLC 2019 OA03.03). Objective response rate (ORR; secondary endpoint) was 44% (11/25). Here we report efficacy analyses in post hoc subgroups by platinum sensitivity. Methods: RESILIENT part 1 was an open-label, single-arm study comprising dose-finding and dose-expansion phases. Eligible patients were aged ≥ 18 y, with an ECOG performance status score of 0/1 and adequate organ function; a single line of prior immunotherapy was allowed. Participants received liposomal irinotecan 70 mg/m 2 or 85 mg/m 2 free base every 2 weeks, with tumor assessments every 6 weeks (RECIST v1.1). Analyses were undertaken for the dose-finding phase recommended dose (RD) in subgroups of platinum-resistant/sensitive patients (with/without progression within 90 days from completion of 1L therapy). Results: During dose finding, 5 patients received liposomal irinotecan 85 mg/m 2 (deemed not tolerable; dose-limiting toxicity) and 12 received 70 mg/m 2 (deemed tolerable; RD for dose-expansion phase in which 13 more patients were included). Analyses included all 25 patients receiving the RD (mean exposure, 13.95 weeks [median 14.86; SD 7.222]). In the platinum-sensitive subgroup (33.3% men; median age 62.0 y) ORR was 53.3% (8/15) and 12-week disease control rate (DCR12wks) was 60% (9/15); in the platinum-resistant subgroup (50% men, median age 58.0 y) both ORR and DCR12wks were 30% (3/10). Overall and progression-free survival (secondary endpoints) are not yet mature. Conclusions: ORR and DCR12wks were numerically higher in platinum-sensitive than in platinum-resistant patients with SCLC who had progressed with platinum-based 1L therapy before receiving 2L liposomal irinotecan 70 mg/m 2 in this phase 2 study. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial vs topotecan, will provide further data. Clinical trial information: NCT03088813.
Incidence of 5-fluorouracil related in cardiotoxicity in patients with head and neck cancer.
Authors: Akhil Rajendra, Vanita Noronha, Vijay Maruti Patil, Amit Joshi, Nandini Sharrel Menon, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

e24123 Background: Combination chemotherapy with cisplatin-fluoropyrimidine backbone is the standard of care for locally advanced head and neck cancer in the neoadjuvant setting. 5-Fluorouracil (5FU) is administered as a continuous intravenous infusion over 5 days. However, 5-FU may induce acute cardiotoxicity preventing its subsequent use. Incidence of 5-FU-induced cardiotoxicity ranges from 0.99 to 19.9% in published studies, which have been assessed predominantly in gastrointestinal malignancies. In the pivotal TAX323 and TAX324 trials, utilizing 5FU (750 mg/m 2 continuous infusion for 5 days), docetaxel and cisplatin (TPF) as neoadjuvant chemotherapy, no cardiotoxicity was reported. We evaluated the development of cardiotoxicity from the use of the TPF regime in our patients with locally advanced head and neck cancer. Methods: Post-hoc analysis of patients treated on the TPF arm of a randomized controlled trial in our institution for locally advanced head and neck cancer in the neoadjuvant setting from 2016 to 2019. Results: 246 patients received TPF neoadjuvant chemotherapy for locally advanced head and neck cancer. Cardiotoxicity occurred in 16 patients; thus, the incidence was 6.5% (95% CI, 3-10%). Two-thirds of the cardiac events occurred in the 1 st cycle. Mean time to onset of symptoms was 109.5 hours (4 th day of the infusion). The most common events were chest pain (9 patients [56%]), asymptomatic bradycardia (5 patients [31%]) and syncope (2 patients [12%]). Dynamic ECG changes were seen in 5 patients with ST-segment elevation myocardial infarction occurring in one patient. Most common rhythm abnormality identified was bradycardia (7 patients) and in most cases, patients were asymptomatic (5 patients) for the same. Only 2 patients had LV dysfunction detected on echocardiography after the event. Cardiotoxicity resolved in 12 patients (75%). Conclusions: 6.5% of patients treated with 5-FU developed cardiotoxicity with most patients developing symptoms by day 4 of the 1 st cycle; chest pain was the most common symptom.
Acral lentiginous melanoma: Population-based analysis of incidence and survival in United States from 1993 to 2013.
Authors: Nishitha Thumallapally, Ahmed Meshref, Mohammed Mousa
Journal: Journal of Clinical Oncology (2020)

e22108 Background: Acral Lentiginous melanoma (ALM) is a rare form of cutaneous melanoma with aggressive nature. This study investigates the incidence and survival patterns in patients diagnosed with ALM in USA from 1993-2013 using data from the Surveillance, Epidemiology, and End Results (SEER) Registry. Methods: The 18 cancer registries of SEER program were used to identify patients diagnosed with ALM according to international classification of diseases for oncology (ICDO-3) codes. Age adjusted incidence rates in addition to 5 and 10-year relative survival rates were calculated. Results: 2189 patients were included in this retrospective study.The age-adjusted incidence rate of ALM was 2.11 per million person-years.Hispanic whites had highest incidence rates of ALM among all racial subgroups ( 2.58, p = 0.005). Incidence of ALM was higher between 2003-2013 compared to 1993-2003 (2.3 vs 1.9).Median age at diagnosis was 61.68 years. 53.9 % were female. Our study population was dominated by Non-Hispanic Whites (69.2%) followed by Hispanic Whites (13.5%), Blacks (8.2%), Asians or Pacific Islanders (7.3%) and other races (1.8%). stage III was the most frequent (24.7%) followed by stage I (20.9%). In terms of tumor thickness, 43.2 % presented with T3 thickness at the time of diagnosis. The ALM 5 - and 10-year survival rates were highest in age &lt; 40, females, T1, non ulcerated, lymph node negative lesions ( p &lt; 0.05). Among racial subgroups, non Hispanic whites had highest survival rates (83 vs 74 % ). Asian/Pacific Islanders (75.1%vs 49.8%) had lowest survival rates followed Hispanic whites ( 76.4 % vs 63.9 ) and Blacks (74.7 vs 71.5 %) ( p = 0.19). Conclusions: ALM is rare subtype of cutaneous melanoma with increased incidence in people of color. Patients present with increased tumor thickness and advanced stage at the time of diagnosis. Poor survival rates are seen among Asian/Pacific Islanders and Hispanic whites.