tbuckley/cabot-search huggingface dataset:
Setting focus on oncology in a German undergraduate medical training program: Our experience with a longitudinal elective <i>Interdisciplinary Oncology</i>.
Authors: Stefanie Zschaebitz, Dirk Jaeger, Eva Caroline Winkler, Niels Halama
Journal: Journal of Clinical Oncology (2020)

11034 Background: Compared to other academic disciplines such as social sciences and humanities, medical school curricula leave limited opportunities to meet individual interests of students. Methods: To allow students to set an individual focus in their MD education, and to promote a sound scientific basis, n = 11 longitudinal electives (“tracks”) were introduced within the Heidelberg Curriculum Medicinale (HeiCuMed) in 2017. The volume of additional training consists of 2 weekly lectures hours for at least 1.5 years of training. Participation in the program has been on a voluntary basis until 2019 and now is obligatory for every student. Results: n = 141 students are currently enrolled within the track “Interdisciplinary Oncology (IO)”. More than n = 50 optional courses are offered each semester covering oncologic subjects such as scientific methods in cancer research, ethical issues in research and clinical practice, communication and clinical skills training. The modular system of the IO elective allows for a wide selection of topics for participating students but also poses a challenge for graded assessments. Conclusions: Conducting a modular elective including graded assessments is feasible. The longitudinal track IO has a high voluntary participation rate and very positive feedback from students. This indicates that our teaching concept is very well suited to address the call for increased choice and specialization in medical curricula in Germany.
Language Bias Among Chinese-Sponsored Randomized Clinical Trials in Systematic Reviews and Meta-analyses—Can Anything Be Done?
Authors: Chen Mao, Mengfeng Li
Journal: JAMA Network Open (2020)

Yuanxi Jia, ScM; Doudou Huang, MD, MPH; Jiajun Wen, MD, MPH; Yehua Wang, MSPH; Lori Rosman, MLS; Qingkun Chen, ScM; Karen A. Robinson, PhD; Joel J. Gagnier, ND, MSc, PhD; Stephan Ehrhardt, MD, MPH; David D. Celentano, ScD, MHS
Genomic heterogeneity of multifocal NSCLC.
Authors: Mingjiu Chen, Haitao Ma, Haoda Yu, Chen Chen, Pingping Dai, Zhiyi He, Pengcheng Li, Yan Zhang, Yan-Fang Guan, Xuefeng Xia, Ling Yang, Xin Yi
Journal: Journal of Clinical Oncology (2020)

e21595 Background: Distinguishing multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) remains a common diagnostic dilemma but critical for developing a therapeutic strategy. Methods: In this study, we analyse genomic features of 584 tissue samples from 258 NSCLC patients with &gt; 1 surgically-resected tumor. NGS was performed using panels of 1021/59 genes. Results: Among 80 patients with definite diagnosis, 23 patients (46 tumors) were diagnosed with IPM. And 57 patients (145 tumors) were MPLC, consisting of 53 synchronous and 3 metachronous tumor pairs. Among 23 IPM tumor pairs, we identified at least one shared somatic mutation. By contrast, 93%(53/57) MPLC tumor pairs exhibited entirely unique mutation profiles in each tumor. Of 57 MPLCs, 4(7%) had no driver alteration ( EGFR, KRAS, BRAF, ALK, ERBB2, MET Exon 14). 9(16%) had a driver in only one of the tumors. In the remaining 44 MPLCs, 40 had unique driver mutation in each tumor. 50%(20/40) had distinct EGFR mutations, the most common combination was L858R and delins in exon 19. Specifically, 8(20%) patients resided ≥3 unique driver mutations simultaneously. This observation indicated that multiple lesions in the same individual can be driven by distinct molecular events. In contrast, 21 available IPM tumor pairs shared the same driver mutation. Pathogenic germline mutations were also analysed. Two were found in 2 MPLCs, involving PLAB2 and BLM, which were both null variants. While there were no pathogenic germline mutations found in IPMs. Regarding the MSI status, all samples from either MPLCs and IPMs displayed MSS, unexpectedly. To further verify the findings above, the remaining 393 samples with uncertain diagnosis were classified into group M (no shared mutation, 218 samples /97 patients) and I (≥1 shared mutation, 175 samples/81 patients). We find the similarity results among all available patients, driver mutation profiles exhibited completely unique and multiple in group M and fully consistent in group I. Conclusions: Taken together, our analyses indicated that the genomic heterogeneity of multifocal NSCLC may be a potential strategy for differentiating IPM and MPLC. This may hold implications for prioritizing therapeutic strategies.
The Hodgkin lymphoma international study for individual care (HoLISTIC): Enhancing decision making in pediatric and adult Hodgkin lymphoma (HL).
Authors: Susan K. Parsons, Angie Mae Rodday, Carlton Scharman, Marc André, Massimo Federico, Jonathan W. Friedberg, Debra L. Friedman, Andrea Gallamini, Annette E. Hay, Peter Hoskin, Peter Johnson, Brad S. Kahl, Frank G. Keller, Kara M. Kelly, Ralph M. Meyer, John A. Radford, John Raemaekers, Pier Luigi Zinzani, Joshua T. Cohen, Andrew M. Evens
Journal: Journal of Clinical Oncology (2020)

e20019 Background: Decision making in HL is complicated by clinical trial results that differ, a growing range of treatment options, and the absence of ideal, objective information on long term outcomes from modern therapy. Methods: We formed an international consortium, HoLISTIC, consisting of 50+ pediatric &amp; adult HL providers, decision scientists, statisticians, epidemiologists, and patient (pt) advocates and are creating a data repository of individual pt data (IPD) from 16 contemporary, pediatric &amp; adult clinical trials for newly diagnosed pts with HL, and 6 large HL registries/survivorship cohorts, the latter enriched with LE data (Table). We will enhance our prior decision model (DM) from group-level data (Parsons S et al. B J Haem 2018) to establish a dynamic HL DM from IPD. Using statistical and simulation modeling of IPD, the enhanced DM will project outcomes of interest, including quality-adjusted life years (QALYs), reflecting both mortality and morbidity. Results will be validated and calibrated against prominent external cohorts (e.g., St. Jude LIFE Cohort, Dutch HL registry). The DM then will be converted to a web-based platform that we will test and evaluate among HL providers and pts at the point of care. Results: To date, we have harmonized IPD from 10 trials (~8,000 HL pts), ranging in size from 165-1925 pts. At diagnosis, median age was 26 y (IQR 18-38); 51.5% were male. 43% had B symptoms, 34% had mediastinal bulk, and 79% had nodular sclerosis histology. Median follow up was 5.0 y (IQR 3.5-7.4). IPD harmonization is ongoing, which will be followed by creation of the enhanced DM. Conclusions: HoLISTIC capitalizes on a multidisciplinary pediatric &amp; adult oncology collaborative, harmonizing extensive IPD by linking data from clinical trials and real world registries/survivorship cohorts. This work will inform questions about the influence of Tx options on both acute and potential long term events and how those options align with pt values and preferences. [Table: see text]
Dose and volume de-escalation for HPV-associated oropharyngeal cancer: Long-term follow-up of the OPTIMA trial.
Authors: Ari Rosenberg, Nishant Agrawal, Alexander T. Pearson, Tanguy Y. Seiwert, Zhen Gooi, Elizabeth A. Blair, John Cursio, Adam Howard, Jeffrey Chin, Corey Christian Foster, Sara Kochanny, Mark W. Lingen, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2020)

6575 Background: Human papilloma virus (HPV) associated oropharyngeal cancer is associated with a favorable prognosis, but standard multimodality treatment is associated with substantial treatment related toxicity. A de-escalation treatment paradigm that optimizes oncologic outcomes while reducing toxicity is needed. We sought to further expound on our published OPTIMA data with long-term follow-up and additional pts subsequently treated using the OPTIMA treatment paradigm. Methods: Long-term follow-up of our institutional de-escalation OPTIMA trial (NCT02258659) and retrospective review of additional patients treated subsequently per OPTIMA outline was performed. Pts were classified as low-risk (LR) (≤T3, ≤N2B, ≤10PYH) or high-risk (HR) (T4, ≥N2c, &gt; 10PYH). Pts received induction chemotherapy (IC) of 3 cycles of dose dense carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (subsequently treated). LR with ≥50% response received low-dose radiotherapy (RT) to 50 Gy. LR with 30-50% response or HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45Gy. All others received full-dose CRT to 75Gy. Results: 108 pts consented and 107 were treated (61 on study; 46 subsequently) from October 2014 through November 2019. 1 pt transferred care post-enrollment. Median follow-up was 36 months (interquartile range 17-45). Median age was 63 years (range 33-84) and 95% were male. 47% were LR and 53% were HR. ≥50% tumor shrinkage occurred in 78/107 (73%) of pts overall, and 37/51 (73%) among LR; 41/56 (73%) among HR. 82% of pts received de-escalated (C)RT. Overall, 94% of pts were alive at last follow-up (98% LR; 89% HR). 3 pts (2 HR and 1 LR) developed disease recurrence (2.7%), with 2 local recurrences and 1 distant recurrence. Likelihood of G-tube placement was 3% in low-dose RT, 35% in intermediate-dose CRT, and 84% in full-dose CRT. Conclusions: IC followed by risk-adapted dose and volume de-escalated treatment for HPV+ oropharyngeal cancer demonstrates excellent oncologic and functional outcomes with long-term follow-up. Supported by Celgene, Alinea benefit supported by Grant Achatz/Nick Kokonas, and National Cancer Institute of the National Institutes of Health (NIH) through Grant Number P30 CA14599. Clinical trial information: NCT02258659 .
一项简单而又决定诊断的体格检查
Authors: 施桂英
Journal: BMJ (2005)

2004年7月21日,一例因发热疑为系统性红斑狼疮而在本院急诊室留观的患者,被家属用车推到我的门诊诊室,要求会诊.患者女,49岁,农民,既往体健,因发热、无力、肌痛及肢体浮肿1个月来院求治.患者每日体温波动在38℃左右,四肢无力,疼痛和浮肿日渐加重,但尿量无明显减少,无皮疹、脱发、关节痛、心慌、咳嗽、气短及其他不适.在当地医院接受过药物治疗(具体不详),病情无改善.本院急诊室已查血和尿常规、心电图及X线胸片等项目均无异常。
Fertility counseling in young patients with colorectal cancer.
Authors: Chengwei Peng, Lena Masri, Scott Sherman, Daniel Jacob Becker
Journal: Journal of Clinical Oncology (2020)

e24081 Background: The incidence of colorectal cancer in patients younger than 50 has been increasing over the past two decades. This demographic shift has important implications for survivorship care, in particular regarding issues of future fertility. Although ASCO has a longstanding recommendation for fertility counseling in patients with cancer, the rates of fertility counseling in younger patients with colorectal cancer are unknown. Methods: Records for new patient visits for colorectal cancer in patients younger than age 55 in a large academic cancer center between 2016 and 2019 were retrospectively queried for patient demographics, disease characteristics, and documentation of fertility counseling. Associations between patient demographic/clinical characteristics and receipt of fertility counseling were explored. Univariate analyses and multivariable logistical regression analyses were performed using SAS v9.4. Results: Among the 136 patients who met inclusion criteria, 37.5% of patients were female, 16.2% were African American, 31.6% had rectal cancer, 20.7% of patients had Medicaid insurance. 63.7% were treated with curative intent. Age ranged from 22-55 (median = 46). Among all patients, 21/136 (15.4%) had documented fertility counseling. Of these, 11/51 (21.6%) patients were female and 10/85 (11.8%) were men. In univariate chi-square analysis, age less than or equal to 40 was associated with fertility counseling (p &lt; 0.001) and curative intent therapy was numerically but not statistically associated with fertility counseling (p = 0.07). In multivariable analysis with logistical regression, age less than 40 (OR = 3.90, 95% CI [1.95, 7.81]), female gender (OR = 2.37, 95% CI [1.16, 4.84]), and curative intent therapy (OR = 3.26, 95% CI [1.14, 9.35]) were associated with fertility counseling. Race, stage of cancer, insurance status, prior exposure to chemotherapy, and colon vs rectal cancer were not associated with fertility counseling. Conclusions: The rate of fertility counseling was very low among patients with colorectal cancer, and exceptionally low among men with colorectal cancer. Despite changes in the demographics of colorectal cancer, it does not appear that appropriate changes have been made in fertility counseling. Additional studies to identify barriers and implementation strategies for fertility counseling are urgently needed in a disease that affects more young patients each year.
The landscape of muti-PIK3CA variations of 10,000 Chinese solid-tumor patients.
Authors: Weiguang Gu, Chengzhi Zhou, Zhuojian Shen, Jian Huang, Chang Qiao, Jinwei Hu, Weifeng Wang, Ming Yao, Kai Wang
Journal: Journal of Clinical Oncology (2020)

e15670 Background: PI3K/mTOR signaling pathway plays a central role in cancer biology. Our study aimed to explore the characteristics of multiple PIK3CA variations in the Chinese patient with solid tumors. Methods: Formalin fixed, paraffin embedded (FFPE) tumor samples and matched peripheral blood from 10,194 Chinese solid tumor patients were collected for next-generation sequencing based 450 genes panel assay. The testing was carried out by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China. Genomic alterations including SNV, short and long Indel, CNV, Fusion/Rearrangement were assessed. Microsatellite stable (MSS) status and TMB (tumor mutational burden) were also acquired by an NGS algorithm. Results: A total of 672 (6%) patients were identified harboring PIK3CA mutations, 93 (13.8%) of them had multiple PIK3CA mutations. Patients with multiple PIK3CA mutations included 51 females and 42 males with a mean age of 56 years old. Tumors with multiple PIK3CA mutations were composed of stage I (N = 14), II (N = 22), III (N = 18), IV (N = 25) and 14 without staging information. Cervical, breast, gastric and colorectal cancers were top ranked multiple-PIK3CA-mutant tumors (21%, 17%, 15%, 12% and 6%, respectively). TMB-H (≥10 mut/Mb) was significantly higher in multiple-PIK3CA-mutant tumors than that in single-PIK3CA-mutant tumors (60% vs 32%, P &lt; 0.001). The MSS status was similar between multiple- and single-PIK3CA-mutant tumors (14% vs 11%). The most common PIK3CA alterations in both multiple- and single-PIK3CA-mutant tumors were E545 (36% vs 28%), H1047 (19% vs 24%) and E542 (16% vs 13%). Noticeably, the frequency of R88 (16% vs 3%, P &lt; 0.0001), E726 (10% vs 0.8%, P &lt; 0.0001), E453 (10% vs 1%, P &lt; 0.0001), and M1043 (9% vs 0.8%, P &lt; 0.0001) mutations were significantly higher in multiple-PIK3CA-mutant tumors than that in single-PIK3CA-mutant tumors. The top 3 most frequent PIK3CA dual mutation combinations were E545K+E726K, H1047R+E726K and E545K+R88Q. Among the co-mutated genes, copy numbers of ERBB2 were less altered in multiple-PIK3CA-mutant tumors than single-PIK3CA-mutant tumors (1% vs 6%, p &lt; 0.05). Conclusions: This study, for the first time, revealed that approximately 13% PIK3CA positive Chinese solid tumor pts harboring multiple PIK3CA mutations. Several novel dual-PIK3CA-mutations were detected and multiple-PIK3CA-mutant pts more likely had high TMB, which may guide potential immunotherapy or PI3K-targeted therapy for multiple PIK3CA Chinese solid tumor patients.
Senescent Cells in Cancer Therapy: Friends or Foes?
Authors: Boshi Wang, Jaskaren Kohli, Marco Demaria
Journal: Trends in cancer (2020)

Several cancer interventions induce DNA damage and promote senescence in cancer and nonmalignant cells. Senescent cells secrete a collection of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP). SASP factors are able to potentiate various aspects of tumorigenesis, including proliferation, metastasis, and immunosuppression. Moreover, the accumulation and persistence of therapy-induced senescent cells can promote tissue dysfunction and the early onset of various age-related symptoms in treated cancer patients. Here, we review in detail the mechanisms by which cellular senescence contributes to cancer development and the side effects of cancer therapies. We also review how pharmacological interventions to eliminate senescent cells or inhibit SASP production can mitigate these negative effects and propose therapeutic strategies based on the age of the patient.
Analysis of cardiac involvement in patients with systemic lupus erythematoms
Authors: Feng-xia Wu, Xiong-yan Luo, Ming-hui Yang, Jing-guo Zhou, Guo-hua Yuan
Journal: BMJ (2008)

Objective To study clinical characteristics in patients of systemic lupus erythematosus (SLE)with cardiac involvement and to assess relevant risk factors contributed to it.Methods Totally,239 patients of SLE were evaluated by cardiogram,echocardiogram and serologic examinations,and those with cardiac involvement were compared to those without it by clinical and laboratory data.Results There were 114 of 239(47.7%)SEE patients with cardiac abnormalities,of whom only 31(27.2%)had cardiac symptoms,including 44 cases(38.6%)with hydropericardium,32(28.1%)with myocardial damage,14 (12.3%)with cardiac valvular lesions,19(16.7%)with cardiac block,and 13 with other cardiac damages.No significant difference in age,gender,course of disease,SLE activity index(SEEDAI)scores,serum levels of auto-antibodies and complement(C3),and so on,were found between 114 SLE patients with cardiac abnormalities and 64 without it,who were:randomly selected from 125 patients of SEE without cardiac damage.But,patients of SLE complicated with pericarditis or myocardial lesions had higher SLEDAI scores and lower serum level of C3 than those without cardiac lesions(both P＜0.05),and relatively longer course of disease was found in those with valvular heart disease.Conclusions Cardiac damage was common in patients with SLE,but most of whom were asymptomatic,and only those with severe and active illness tended to develop pericarditis and myocardial damage and those with longer course were liable to have valvular heart disease.

Key words: 
Lupus erythematosus,systemic; Heart; Risk factor
Development of a measuring tool for elderly care service needs in the community and its reliability and validity
Authors: Ji Gu, Minjie Jin, Ping Lu, Bo Gao, Yuanyuan Ge, Shanshan Zhao
Journal: BMJ (2019)

Objective
To develop a measuring tool for the elderly care service needs in the community.


Methods
Based on the literature search and Delphi expert consultation, a measuring tool for elderly care service needs was developed. The reliability (internal consistency coefficient) and validity (surface validity, content validity, criterion-related validity) of the developed measurement tool were evaluated with on-site expert consultation and the cross-sectional survey.


Results
A 11-dimension measurement tool was developed, which covered physical health, mental health and desires for old-age support assessment. The reliability evaluation showed that there was significant correlation (P<0.05) among the measurement dimensions of the physical health and the mental health of the elderly in community. The validity evaluation showed that the measurement methods for the measurement dimensions of the elderly care needs, including the evaluation items, evaluation methods, and rating methods, all got below 2 scores in applicability assessment, and the measurement methods of the self-care ability, vision, the self-willingness/information expression of the elderly, the ability of the elderly to understand the willingness/information expressed by others, and the ability to provide family care were all supported by more than 50% experts, which indicated that the surface validity and content validity were good. There was a significant positive correlation between the living places of the elderly and the needsof elderly care services (r=0.214, P<0.01), and there were significant correlations between all measurement dimensions with the living place except anxiety (P<0.05), which indicated that the measurement tool had an acceptable criterion-related validity. The consistency of self-supporting willingness, the family willingness to care for the elderly with the current old-age care place were relatively poor (Kappa=0.063, P=0.007; Kappa=0.051, P=0.006).


Conclusion
The overall performance of the measurement tool for the elderly care service needs developed in this study is acceptable. It has been approved by both the elderly care service suppliers and the elderly care service needs evaluators. It also shows some internal consistency in measurement results of the demanders, and is consistent with the actual living place.


Key words: 
Elderly care service needs; Measurement tool; Reliability; Validity
Cancer-IgG upregulation of radioresistance in non-small cell lung cancer patients and cell lines.
Authors: Guangying Zhu, Xiongtao Yang, Wang Guohui, Jing You
Journal: Journal of Clinical Oncology (2020)

e21013 Background: Immunoglobulin G (IgG) is produced by B lymphocytes which is an important effector molecule of human immunity. However,our collaborators in China Peking University have found that malignant tumor cells can also express IgG (cancer-IgG). This study was designed to investigate the relationship between cancer-IgG and radiosensitivity and to explore its possible mechanisms in NSCLC. Methods: First, the expression of IGHG1 (immunoglobulin heavy constant gamma 1, IGHG1) and cancer-IgG in NSCLC and their relationship with clinicopathological features and prognosis were analyzed by TCGA(The Cancer Genome Atlas, TCGA), GEO(Gene Expression Omnibus, GEO) databases and immunohistochemistry. Secondly, after silencing the expression of cancer-IgG, cell scratch test, transwell, clone formation and apoptosis experiments were performed to observe the changes of EMT and radiation sensitivity of tumor cells after irradiation. Finally, the key proteins of PI3K/Akt signaling pathway and EMT-related proteins were detected by western blot and real-time PCR. Results: 1. The expression levels of IGHG1 and cancer-IgG in NSCLC were significantly higher than those in normal lung tissues, and high expression of IGHG1 and cancer-IgG were factors of poor prognosis. And cancer-IgG was closely related to clinical stage (P = 0.042), T stage (P = 0.044) and metastasis (P = 0.007). 2. Cell scratches and transwell experiments showed that the cell migration and invasion ability of si-control+IR group were significantly enhanced, but in si-Cancer-IgG+IR group were significantly lower than si-control+IR group. 3. Cloning formation experiments showed that the number of cell clones formed in the si-cancer-IgG group was significantly less than that in the control group under 2-6 Gy irradiation. Apoptosis results showed that the apoptosis rates of si-control group, si-Cancer-IgG group, si-control+IR group and si-Cancer-IgG group were 6.36±1.69%, 21.33±1.21%, 23.31±0.96% and 52.69±2.33% respectively. The apoptotic cells in the Si-cancer-IgG group were significantly more than the si-control group. (P &lt; 0.01). 4. Western blot results showed that p-AKT, p-GSK3β, bcl2 and Vimentin were significantly decreased in si-Cancer-IgG+IR group compared with si-control+IR, and the expression levels of BAD and E-cadherin were increased. Conclusions: Cancer-IgG may mediate radiation-induced EMT and radiotherapy resistance through the PI3K/AKT pathway.