tbuckley/cabot-search huggingface dataset:
DNA damage and repair gene panel as a biomarker of immune checkpoint inhibitor response.
Authors: Ming Huang Chen, Yi-Ru Pan, Chiao-En Wu, Yi Chen Yeh, Yi-Ping Hung, Yee Chao, Yu-Chao Wang, Chien-Hsing Lin, Jason Chia-Hsun Hsieh, Chun-Nan Yeh
Journal: Journal of Clinical Oncology (2020)

e15052 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although predictive biomarkers for efficacy still remain largely unknown. Methods: This study aims to develop a novel gene panel by selecting DNA damage and repair (DDR) genes from the Catalogue of Somatic Mutations in Cancer (COSMIC) database and perform validation using publicly available cohorts. Association between the DDR gene panel and tumor mutation burden or microsatellite status were analyzed from The Cancer Genome Atlas (TCGA) database. To further improve the clinical accessibility of the DDR gene panel, we analyzed the feasibility of its predictive value using cell free DNA in from 64 patients receiving ICIs. Results: The 193 mutated DDR genes in various cancers were chosen from the COSMIC databank, and the DDR genes found to individually predict a response rate &gt; 50% in publicly melanoma cohort (Van Allen, et al) were selected. Eighteen DDR genes were selected as the DDR gene panel. The prevalence of the DDR gene mutations and predicted response rate of ICIs were validated in other three publicly available cohorts (Hugo et al, Synder et al, and Rizvi et al.). Tumor mutational burden and high microsatellite instability were positively associated with mutations of the 18 DDR genes for most cancers. Further validation was performed using cell-free DNA from cancer patients receiving ICIs. This DDR gene panel was detected in approximately 30% of various cancers, achieving a predicted response rate of approximately 60% in patients receiving ICIs. Conclusions: Our developed DDR gene panel can serve as a novel and reliable biomarker that can provide critical information for predicting the response to ICIs in cancer patients and guide the appropriate administration of ICIs in clinical practice.
Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers
Authors: Yeon Wook Kim, Hye-Rin Kang, Byoung Soo Kwon, Sung Yoon Lim, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Kyung Won Lee, Jae Ho Lee, Choon-Taek Lee
Journal: European Respiratory Journal (2020)

Background Although lung cancer screening using low-dose computed tomography (LDCT) is now widely used in clinical practice, the characteristics and outcomes of diagnostic procedures related to screen-detected nodules in never-smokers remain unclear. We aimed to determine the incidence of nodules considered for invasive biopsy and evaluate the final diagnoses and procedure-related complications in never-smokers in comparison to ever-smokers who underwent LDCT screening. Methods We evaluated 37 436 asymptomatic adults (17 968 never-smokers and 19 468 ever-smokers) who underwent LDCT screening for lung cancer between January 2009 and December 2018 at a tertiary centre in South Korea. The rates of invasive diagnostic procedures for detected nodules and related complications, and the diagnostic outcomes were determined in the never-smoker and ever-smoker groups. Results Among the never-smokers, 2908 (16.2%) out of 17 968 had positive nodules. Overall, 139 (0.77%) out of 17 968 never-smokers and 194 (1.00%) out of 19 468 ever-smokers underwent invasive biopsy (p=0.022). Lung cancer was diagnosed in 84 (0.47%) out of 17 968 never-smokers and 123 (0.63%) out of 19 468 ever-smokers (p=0.032). The proportions of participants diagnosed with benign disease after invasive biopsy (false-positive) were 50 (0.28%) out of 17 968 and 69 (0.35%) out of 19 468 in the never-smoker and ever-smoker groups, respectively (p=0.191). Multivariate analyses revealed no significant associations of smoking with the risk of a false-positive diagnosis (OR 0.98, 95% CI 0.62–1.57) and complications (OR 1.33, 95% CI 0.65–3.73) after biopsy. Of the 84 never-smokers with lung cancer, 82 (97.6%) had adenocarcinoma, and 75 (89.3%) were in stage I with a favourable prognosis. Conclusions LDCT screening in never-smokers resulted in a notable detection rate of lung nodules, which warranted invasive biopsy. The lung cancer detection rate was lower in never-smokers than in ever-smokers. However, no significant differences in the false-positive and complication rates were observed between the two groups. Accordingly, a more specifically tailored management strategy is needed for screen-detected nodules in Asian never-smokers.
Feasibility of switching to S-1 after other fluoropyrimidine-related cardiotoxicity during chemotherapy for solid tumors.
Authors: Pia J. Osterlund, Sampsa Kinos, Päivi Halonen, Leena-Maija Soveri, Johannes J Kwakman, Tapio Salminen, Raymond S. McDermott, Per Pfeiffer, Eetu Heervä, Gabor Liposits, Rebecka Röckert, Annika Ålgars, Raija S. Kallio, Halfdan Sorbye, Petra Flygare, Helga Hagman, Carl-Henrik A. Shah, Erik D. van Werkhoven, Bengt Glimelius, Cornelis J. A. Punt
Journal: Journal of Clinical Oncology (2020)

7037 Background: Fluoropyrimidines (FP) are the cornerstone of chemotherapy in many solid tumors and linked to cardiotoxicity (CarTx) in about 5% (Polk, Cancer Treat Rev 2013), often leading to FP discontinuation. CarTx may be less common with S-1 and successful switch from other FP has been reported (Kwakman, EJC 2017). Methods: This 6-country, 12-center, cohort study included patients with solid tumors (ICD10 C15-C21, C24-25, C50, C80) who experienced FP-related CarTx. Primary endpoint was recurrent (R) CarTx during S-1 therapy after switch from any other FP. Results: CarTx during capecitabine (n = 124), continuous (n = 13) or bolus 5-fluorouracil (n = 4) was reported for 141 patients who switched to S-1 therapy. CarTx was chest pain including vasospasm without cardiac findings (55%), acute coronary syndrome or myocardial infarction (32%), atrial fibrillation (4%), heart failure/cardiomyopathy (4%), tachy-/bradycardia (3%), and/or other (15%). CarTx was grade 3-4 in 55%, appeared on cycle 1-2 in 89%, and at median 4 days (range 0-466) from FP initiation (Table). Causality was judged related in 26%, probable in 60%, and possible in 14%. Action with FP causing CarTx was permanent discontinuation in 91%. Treatment intent was curative in 70%. Cumulative incidence of RCarTx with S-1 was 3.5% (CI 95%, 1.2-8.4%) and median time to R-CarTx was 11 (range 6-195) days. Four (out of 141) had grade 1 and one grade 2 R-CarTx. Three were judged possibly related to S-1 and 2 not related. S-1 was discontinued in one patient and continued in 4 (for 63-252 days) without action (n = 2), with dose reduction (n = 1), or delay (n = 1). There were no differences in demographic or risk factors regarding R-CarTx on S-1 (Table). Conclusions: FP-related CarTx is often severe, occurs early, and leads to permanent FP discontinuation. Switching to S-1-based therapy is safe, with, at the most, grade 1-2 R-CarTx in only 3.5%, and rarely leads to treatment discontinuation (0.7%), allowing patients to continue on an FP-based regimen. Clinical trial information: NCT04260269 . [Table: see text]
Abstract 16497: Selective Succinate Dehydrogenase Inhibition at the Area at Risk With Intracoronary Malonate Reduces Reperfusion Injury in Pigs Submitted to Transient Coronary Occlusion
Authors: Laura Valls-Lacalle, Ignasi Barba, Elisabet Miro-Casas, Marisol Ruiz-Meana, David Garcia-Dorado, Antonio Rodriguez-Sinovas
Journal: Circulation (2017)

Introduction: Previous studies demonstrated that succinate dehydrogenase (SDH) inhibition with malonate during reperfusion reduces infarct size in isolated mice hearts submitted to global ischemia....
Hrd in ovarian cancer: Defined today, evolving for the future.
Authors: Markus Eckstein, Kenneth Joel Bloom, Peter Riccelli, Frank Policht, Derry Mae Keeling, Jordan Clark
Journal: Journal of Clinical Oncology (2020)

e18052 Background: Homologous Recombination Repair (HRR) gene mutations result in Homologous Recombination Deficiency (HRD) associated with increased risk of high grade serous ovarian (HGOC) cancer and subsequent response to PARP inhibitors (PARPi). Traditionally, HRD has been determined by testing for germline and/or somatic BRCA1/2 mutations. Today, a growing number of HRR gene mutations are known to result in HRD and genomic instability, thus being a suitable target for PARPi. Therapy response to PARPi is highest in BRCA-mutant followed by HRD + /non-BRCA-mutant HGOC. Today, no standard HRD testing methods exist, causing confusion for physicians, and leading to poor outcomes for missed PARPi eligible patients. Thus, there is need to understand HRD testing utilization and methods in HGOC to inform best practices and optimize HRD testing in the clinic. Methods: We assessed the testing landscape for determining HRD status in ovarian cancer using a data set of 8,400 newly diagnosed and metastatic ovarian cancer patients in the US from Q3-2018 through Q2-2019 identified from Diaceutics’ proprietary Global Diagnostic Index (GDI). Analysis of real-world BRCA1/2 and NGS associated testing data and laboratory profile mapping exercise of 82 US labs was carried out using Diaceutics proprietary methods and data sources to evaluate BRCA1/2 and/or HRD germline/somatic testing rates, test availability, and test panel HRR gene composition. Results: Overall, germline mutation testing rates were 3x greater than somatic testing rates. Excluding BRCA1/2, 67 labs offered comprehensive solid tumor NGS panels capable of measuring HRD with varied HRR gene target composition. Across 34 labs, 5 HRR genes were commonly found on panels: PALB2, ATM, BARD1, BRIP1 and CHEK2. 3 labs currently offering panels explicitly intended for HRD determination only include BRCA1/2 and at least one genomic instability marker (loss of heterozygosity, large-scale state transitions or telomeric allelic imbalance). Conclusions: Lack of standardized HRD panels and low testing rate identifying patients with somatic mutations in BRCA1/2 and other HRR genes is leading to poorer outcomes for missed patients eligible for PARPi’s. As clinical evidence linking HRD status with PARPi efficacy grows in ovarian as well as prostate and pancreatic cancer, Diaceutics recommends organizations such as ASCO, CAP or AMP establish defined universal HRD testing panels including relevant somatic/germline HRR genes and BRCA1/2 as well as genomic instability markers and educate stake holders aiding harmonization and ultimately, better treatment outcomes.
血清钾异常的临床分析
Authors: 谢莉, 刘凤奎
Journal: BMJ (2008)

人体体液中无机物与部分以电解质形式存在的有机物统称为电解质.血液中重要的电解质主要有钾(K+)、钠(Na+)、钙(Ca2+)、镁(Mg2+)、氯(Cl-)、碳酸氢盐(HCO3-)等.钾离子是维持细胞生理活动的主要阳离子,正常人体内含钾最约为50～55 mmol/kg,其中98%存在于细胞内,为细胞内液中最多的阳离子.组织细胞内钾平均浓度为150 mmol/L,红细胞内钾浓度约为105 mmol/L,血清中仅为3.5～5.5 mmoL/L.人体钾盐90%从食物摄入,被肠道吸收入血,吸收入血后90%从肾脏排出体外,汗液中含有少量钾.
Efficacy of tumor treating fields (TTFields) in elderly patients with newly diagnosed glioblastoma (GBM): Sub-group analysis of the phase III EF-14 trial.
Authors: Zvi Ram, Chae-Yong Kim, Jay-Jiguang Zhu
Journal: Journal of Clinical Oncology (2020)

e24019 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma. In the EF-14 [NCT00916409] phase 3 GBM study, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. The aim of the following post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. Methods: All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse events were compared between the TMZ + TTFields arm and the TMZ alone arm. Results: The median age was 69 (range: 65-83), 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TTFields + TMZ versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P &lt; 0.0236). Median OS was 17.4 months versus 13.7 months in the TTFields + TMZ versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P &lt; 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TTFields + TMZ and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields. SAEs were considered related to TMZ or to the underlying disease. Grades 1-2 skin AEs were observed in 51% of patients. Conclusions: Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ + TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade 3-4 toxicity. Clinical trial information: NCT00916409 .
Advanced Lung Cancer Inflammation Index: Prognostic value in a retrospective lung cancer cohort.
Authors: Konstantinos N. Syrigos, Stavroula Patsilinakou, Dimitra Grapsa, Evangelia Chrysanthopoulou, Ioannis Gkiozos, Nikolaos Kavantzas, Ekaterini Politi
Journal: Journal of Clinical Oncology (2020)

e21624 Background: As shown in recent studies, inflammation plays a key role in lung cancer (LC) pathogenesis and evolution, while the potential prognostic and predictive value of various inflammation markers in different disease stages is being extensively studied. We herein aimed to further evaluate the potential prognostic value of a new inflammation marker (ALI, Advanced Lung Cancer Inflammation Index = BMI x Alb / NLR), which combines previous markers of systematic inflammation with markers of nutrition or cachexia at the time of LC diagnosis. Methods: The medical records of 67 patients, diagnosed with LC in Sismanoglio Athens General hospital, within a two-year period (January 2016-January 2017) were retrospectively studied. Demographic, clinicopathological and laboratory features of patients, including pre-treatment ALI, were recorded and correlated with prognosis (overall survival, OS). Results: A total of 67 patients were included with a mean age of 60 (± 8) years. The majority of cases were men (39/67,58.2 %), with positive smoking history (62/67, 92.5%), performance status (PS) 1-2 (43/67, 64.2%) and disease stage IV (54/67, 80.6%). Adenocarcinoma was the commonest histological type observed (19/67, 28.5%). Values of ALI ranged from 7.8 to 37.2 (mean: 21±6). The cut-off point of ALI was 19 (based on ROC curve analysis) and patients were divided into two groups: those with ALI &lt; 19 and those with ALI ≥ 19. In univariate analysis, PS and the presence of metastatic disease, as well as ALI values &lt; 19, were all correlated with reduced survival (p = 0.002, p = 0.028 and p = 0.018, respectively). In multivariate analysis, PS was the only parameter that retained its statistically significant correlation with an adverse prognosis (p = 0.048), although its prognostic significance was increased when combined with ALI. Conclusions: Although failing to confirm an independent prognostic value for ALI, the results of our study suggest that combination of ALI with standard prognostic predictors such as PS may improve prediction of patients’ survival. Additional prospective studies are warranted to validate the prognostic significance of this promising biomarker and expand its use in routine practice.
Mental Health of Young Physicians in China During the Novel Coronavirus Disease 2019 Outbreak
Authors: Weidong Li, Elena Frank, Zhuo Zhao, Lihong Chen, Zhen Wang, Margit Burmeister, Srijan Sen
Journal: JAMA Network Open (2020)

A limitation of this study is that our sample consisted of first-year training physicians in China; studies in other physician populations are needed to understand the mental health effects of the COVID-19 pandemic on physicians more broadly.With most new cases now outside China, ensuring that physicians receive appropriate support and access to mental health services is increasingly imperative, for their own well-being, as well as that of their patients and the global community.
母乳喂养的益处和技巧
Authors: 王惠珊, 连光利, 朱丽琳
Journal: BMJ (2008)

王惠珊:今天跟大家讨论的是母乳喂养.大家都知道,母乳喂养的孩子身体特别好,但是在母乳喂养的过程中,很多家长会提出一些问题和困难,需要社区医生及时介入,给家长一些帮助,使这些母亲在早期能够母乳喂养成功。
An increase in serum choline levels to predict progression-free survival (PFS) in patients (pts) with advanced cancers receiving pembrolizumab.
Authors: Geoffrey Alan Watson, Wenjiang Zhang, Zhihui (Amy) Liu, Anna Spreafico, Aaron Richard Hansen, Philippe L. Bedard, Stephanie Lheureux, Albiruni Ryan Abdul Razak, David W. Cescon, Marcus O. Butler, Wei Xu, Tak Mak, Lillian L. Siu, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2020)

3102 Background: Recent work from our laboratory demonstrated that T cell-derived acetylcholine induces vasodilation and increases T cell migration to infected tissues in response to viral infection (Cox et al. Science 2019). Choline acetyltransferase catalyzes the production of acetylcholine from choline and acetyl-CoA, however acetylcholine is challenging to quantify due to its extremely short half-life while choline is stable. This study is the first reported attempt to correlate serum choline levels in patients (pts) with advanced solid tumors receiving pembrolizumab with treatment outcomes. Methods: Blood samples were collected pre-treatment in 106 pts treated with pembrolizumab 200 mg IV Q3W in the investigator-initiated INSPIRE study (NCT02644369). Of these, 81 pts had on-treatment blood samples collected at week 7 (pre-cycle 3). Serum choline was analyzed with an HPLC-tandem mass spectrometry assay. PD-L1 staining was performed in baseline tumor tissues using 22C3 antibody and scored using modified proportion score. Tumor mutational burden (TMB) was calculated based on number of nonsynonymous mutations detected using whole exome sequencing. Multivariable Cox models were used to assess the impact of choline on PFS and OS, while adjusting for cohort, PD-L1 expression and TMB. Results: This pan-cancer group of 106 pts (median age 55, 62% females) comprised of 5 cohorts: squamous cell carcinoma of the head and neck = 19 pts, triple negative breast cancer = 22, high grade serous ovarian cancer = 21, melanoma = 19, mixed solid tumors = 32. With a median follow-up of 11 months, the median PFS = 1.9 months and median OS = 13.9 months for the entire cohort. In univariable analysis adjusted by cohort, baseline serum choline levels in 106 pts did not correlate with PFS or OS. However, an increase in serum choline level at week 7 compared to pre-treatment (D choline) in 81 pts was significantly associated with a better PFS (aHR 0.49, 95% CI 0.28-0.85, p = 0.01), and a trend towards a better OS (aHR 0.57, 95% CI 0.32-1.03, p = 0.064). In multivariable analysis, D choline remains significantly associated with an improved PFS (p = 0.0087) after adjustment for cohort, PD-L1 and TMB. Conclusions: This is the first exploratory report of serum choline levels in pan-cancer pts receiving pembrolizumab. The association between improved PFS and D choline suggests a possible role for the cholingeric system in the regulation of antitumor immunity. Further nonclinical and clinical studies are required to validate this finding.
Treatment of chronic obstructive pulmonary disease with salmeterol/fluticasone propionate and community intervention
Authors: Bing Zhang, Yu-long Zheng, Su-hua Yang, Li-yang Zhou, Shu Liu, Yuan-qiang He
Journal: BMJ (2011)

Objective To investigate the effects of salmeterol/fluticasone (seretide) combined with community intervention on lung function and quality of life of chronic obstruetive pulmonary disease (COPD) patients in the stable period.Methods 96 cases with COPD in the stable period were divided into two groups randomly:Group A was treated only by seretide for six months,group B was treated by seretide combined with community intervention (health education,psychological intervention,exercise training,and nutritional guidance).6 months later,the lung function was determined and the quality of life was assessed by SGRQ.Results The lung function and the score of the quality of life in two groups after treatment [Group A:(1.78 ±0.16)L,(65 ±9)％ and 40 ± 18,36 ± 16,125 ±40;group B:(2.05 ±0.28)L,(73 ±9)％ and 21 ± 10,20 ± 11,58 ± 28,respectively] were improved than those before treatment [Group A:(1.59 ±0.15),(58 ±7) and 63 ±22,50 ±24,167 ±68;group B:(1.61 ±0.14)L,(58 ± 8)％ and 62 ±22,48 ± 22,163 ± 67,respectively] (P ＜ 0.05 );The lung function and the score of the quality of life in B group were improved than those in A group after treatment ( P ＜ 0.05 ).Conclusions Using community intervention combined with seretide in treatment of COPD patients has better effect than the single use of seretide therapy,it improves lung function and quality of life.It is a safe treatment method and worthy to spread widely.

Key words: 
Pulmonary disease; chronic obstructive; Prognosis; Community intervention
医者典范 总编楷模
Authors: 游苏宁
Journal: BMJ (2011)

我国著名的心血管病及老年医学专家,北京医院名誉院长,中国共产党的优秀党员,中华医学会系列杂志杰出的总编辑钱贻简教授,因病于2011年7月6日在北京逝世,享年86岁.7月12日清晨,全国各界的代表和中华医学会系列杂志的编辑们前往北京医院送别钱老,在告别室中摆放着中华医学会、中华医学会杂志社以及众多中华医学会系列杂志送来的花圈.7月21日,北京医院隆重召开了缅怀钱贻简教授座谈会.卫生部副部长黄洁夫、北京医院院长林嘉滨、笔者等近百人参加了座谈会。
重症急性胰腺炎死亡一例分析
Authors: 翁钦永, 邹志强
Journal: BMJ (2009)

患者女,43岁,因腹痛、腹泻2 d于2008年6月9日入院.入院前2 d进食虾、粽子后中上腹持续性闷痛,伴腹胀和恶心,无畏冷和发热,无反酸、嗳气、呕血和便血.入院时患者神志清楚,急性病容.体温39.2℃,呼吸30次/min,脉搏123次/min,血压130/92 mm Hg(1 mm Hg=0.133 kPa),血糖13.7 mmol/L.心、肺未见异常,无急性呼吸窘迫综合征(ARDS)征象。
深静脉血栓形成的治疗
Authors: 张柏根
Journal: BMJ (2008)

静脉血栓形成是由静脉腔内血液异常凝结引起的病症,可发生在上、下腔静脉,后者包括浅静脉和深静脉.深静脉血栓形成(deep venous thrombosis,DVT)尤以下肢最多见.DVT急性期,可因血栓繁衍致静脉阻塞进行性加重,由股白肿进展为股青肿,造成肢体静脉性坏疽。