tbuckley/cabot-search huggingface dataset:
Association of tumor mutational burden with age in solid tumors.
Authors: Zhuang Yu, Jing Wang, Lingxin Feng, Xue Yang, Qi Qi, Wenqi Li, Xing Zhang, Minhui Ge, Huijuan Qin
Journal: Journal of Clinical Oncology (2020)

e13590 Background: Immunotherapy is becoming one of the promising treatments for cancer administration, and several studies indicated a better outcome was received in patients with high tumor mutation burden (TMB). The distribution of TMB is still unknown and this study aimed to analysis the association between TMB and age especially in East Asian populations. Methods: In our study, TMB value was measured as the numbers of synonymous, nonsynonymous mutations and InDels by next generation sequencing with 539 genes panel in tumor tissue. TMB-H was defined as highest mutation load quintile (top 20%) in each cancer type. The association between TMB and age in 874 patients was investigated including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases, respectively. Spearman rank correlation analysis, Mann-Whitney U-test and Fisher’s exact test were used for statistical analysis. Results: A significant correlation between TMB and ages was observed in patients with solid tumors (r = 0.204, p = 1.263×10 −9 ). The median age of included patients was 60 years-old. Based on nonparametric test, the value of TMB in patients with liver cancer ( p = 2.310×10 −4 ), gastric cancer ( p = 0.029) and lung cancer ( p = 0.001) aged ≥ 60 years-old was significantly higher than the corresponding patients aged &lt; 60 years-old. No significant differences of TMB values were found between patients &lt; 60 and ≥ 60 years-old in bile duct cancer ( p = 0.419), colorectal cancer ( p = 0.075), pancreatic cancer ( p = 1), melanoma ( p = 0.952) and glioma ( p = 0.720). The TMB-H ratio in patients with liver ( p = 0.049) and gastric ( p = 0.015) cancer aged &lt; 60 years old was significantly lower than patients aged ≥ 60 years-old. Conclusions: Our study indicated the TMB value and TMB-H ratio were relatively higher with ages ≥ 60 years old in specific tumors, which might provide useful information to guide precisely the the application of PD-1 or PD-L1 inhibitors. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Comparison of the tumor cells proliferative activity in donor tissue and samples of xenograft generations.
Authors: Ekaterina A. Lukbanova, Evgeniy N. Kolesnikov, Mikhail A Kozhushko, Sergei Kit, Roman E. Myagkov, Aleksandr E. Anisimov, Anna S. Goncharova, Tatiana P. Protasova, Nikolay S. Karnaukhov, Ekaterina V. Zaikina, A. V. Volkova, M. V. Mindar, Sergey Yu. Tkachev, D. V. Khodakova, Aleksey Yu. Maksimov, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2020)

e15619 Background: Esophageal cancer is a common tumor of the mucous layer of the esophagus and the sixth most common cause of cancer deaths worldwide. Studying the mechanisms of its occurrence and development and the search for new approaches to its prevention and treatment are relevant. Such studies require a reliable experimental basis with such an important component as the use of animal models of cancer. In vivo models are an important tool both for testing new drugs and for studying the mechanisms of disease development. The purpose of the study was to create a patient-derived xenograft (PDX) model of esophageal cancer and to evaluate the proliferative activity of cells in the donor tumor and in xenograft samples in a series of successive generations. Methods: A PDX model of esophageal cancer was created by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the distal esophagus of BALB/c Nude athymic mice. The tumor histotype was confirmed histologically (hematoxylin and eosin staining). The proliferative activity of cells was evaluated by immunohistochemistry (IHC) with anti-Ki-67 antibodies. Results: Histological identity of xenograft samples and the donor tumor was confirmed. IHC showed an increase in the proliferative activity index in samples of transplanted tumors compared to the donor material: 12.4% in the primary tumor and 58%, 65.2%, 54.2% and 60.7% in generations 1, 3, 4 and 5, respectively. Conclusions: Histological characteristics of the donor tumor are preserved in all PDX models. The study demonstrated an increase of the proliferative activity in the first PDX generation compared to the primary tumor which persisted in the subsequent models.
Hospitalizations following cancer diagnosis: National values for frequency, duration, and charges.
Authors: Michael T. Halpern, Fanni Zhang, Lindsey Enewold
Journal: Journal of Clinical Oncology (2020)

12039 Background: US medical care costs for cancer are projected to be $158 billion in 2020. Hospitalization is a substantial component of these costs; however, little is known about national patterns of hospitalization among individuals with cancer. This study used Medicare data to determine national rates and charges for hospitalizations among older cancer patients. Methods: We used data from 100% of individuals diagnosed with cancer in SEER-Medicare in the most recent 5 years available, 2011-2015. Analyses determined proportion of patients hospitalized, number/duration of hospitalizations, and charges by patient clinical and sociodemographic characteristics within 12 months of diagnosis. Results: Among 307,944 unique patients, 65% were hospitalized in the first year following diagnosis. Rates ranged from 34% for patients with in situ disease to 82%-84% for patients with advanced disease; 31% had 2 or more hospitalizations. Hospitalization rates were lowest among skin melanoma (25%) and breast (42%) cancer patients, highest for brain/nervous system (97%) and ovarian (96%) cancer patients. Hospitalized patients had a mean of 2.1 hospitalizations; mean days per hospitalization within 12 months was 8.8 (median 4). Duration of hospitalization varied little by stage at diagnosis. Mean days per hospitalization was shortest for thyroid and prostate cancer patients (5.7 &amp; 6.0 days), longest for colorectal cancer and leukemia patients (10.6 &amp; 11.3 days). DRGs varied substantially by cancer type; DRG for chemotherapy administration was more frequent among hospitalizations for patients with hematologic malignancies or distant stage disease. Mean Medicare charge (2016 $) per hospitalization was $67,368 (median $41,973), and was lowest for breast cancer patients ($48,021), highest for leukemia patients ($91,799). Patient charges per hospitalization averaged $1107 (median $1317) and showed little variation by cancer type or stage. Conclusions: Most older individuals experience at least one hospitalization within 12 months of cancer diagnosis. Frequency, duration, and charges of hospitalizations vary by cancer type and stage. This nationally representative information will aid in projecting cancer care costs and potential economic impacts of new therapies and treatment program.
连续硬膜外麻醉用于分娩镇痛90例临床分析
Authors: 张玉春, 田艳峰
Journal: BMJ (2012)

分娩是正常的生理现象,很多人对分娩感到紧张和恐惧,有的孕妇因为在产程中无法忍受宫缩疼痛而选择剖宫产.有的孕妇则干脆拒绝阴道试产,直接选择了剖宫产,致使剖宫产率不断上升[1].本院自2008年3月起开展分娩镇痛,效果良好.现将结果报道如下. 关键词：镇痛,产科
Expression of cytokeratin19 mRNA and integrin alpha v beta 3 in breast cancer patients with negative axillary lymph nodes
Authors: Long-zhou Chen
Journal: BMJ (2009)

Expression of cytokeratin19(CK19)mRNA was detected by reverse transcription-PCR in bone marrow and integrin α_vβ_3 was detected by immunohistochemistry(IHC streptavidin-biotinperoxidase SP)in breast tissue from 62 breast cancer patients with negative axillary lymph nodes.Out of 62 patients 15cases(24%)presented positive CK19,in which all had positive integrin α_vβ_3;36 cases(58%)presented positive integrinα_vβ_3.Two markers were positively correlated with each other(kappa=0.6839,P＜0.05),and correlated with the size of tumor(P＜0.01).The results indicate that combined detection of CK19 in bone marrow and integrin α_vβ_3 in cancer tissues may be helpful for guiding therapy and estimating prognosis in breast cancer patients with negative axillary lymph nodes.

Key words: 
Keratins; Breast neoplasms
Immune functions in premature ovarian failure patients undergoing sequential therapy of puerarin and medroxyprogesterone
Authors: Jinhui Zhang, Hongling Du
Journal: BMJ (2016)

Forty premature ovarian failure(POF)patients with positive antiovary antibody (AoAb) underwent puerarin and progesterone sequential therapy from January 2012 to December 2014. Patients received 12 cycles of sequential therapy, each cycle consisted of puerarin 1 tablet q. d from d1 to d28 and medroxyprogesterone acetate 10 mg q. d from d19 to d28. Serum AoAb, antinuclear antibody (ANA), CD3+ , CD4+ and CD4+ /CD8+ , CD8+ T lymphocytes and CD19+ B lymphocytes were measured before and after treatment, perimenopausal period was evaluated with Kupperman score. Results showed that the Kupperman score after treatment was decreased from (48±18) to (21±14) (P <0.05), and 14 cases were cured (35%); the positive rates of ANA (from 90% to 45%) and AoAb (from 100% to 35%) were significantly decreased after treatment (P<0.05) and the AoAb concentrations were also significantly decreased [from (6.9±2.4) to (3.7±2.5) kU/L, P<0.05]; CD8+ increased significantly (P<0.05), CD3+ , CD4+ T lymphocytes and CD19+ B lymphocyte counts, and CD4+ /CD8+ ratio were significantly decreased after treatment (all P<0.05). Kupperman score changes were positively correlated with changes of ANA and AoAb, CD3+ and CD4+ T lymphocytes (r=0.391, 0.717, 0.412, 0.673 and 0.637, all P<0.05); and negatively correlated with the number of CD8+ T cells (r=-0.657, P<0.05).


Key words: 
Primary ovarian insufficiency; Puerarin; Antibodies
Intervention combining nurse navigators (NNs) and a mobile application versus standard of care (SOC) in cancer patients (pts) treated with oral anticancer agents (OAA): Results of CapRI, a single-center, randomized phase III trial.
Authors: Olivier Mir, Marie Ferrua, Aude Fourcade, Delphine Mathivon, Adeline Duflot-Boukobza, Sarah Naomie Dumont, Eric Baudin, Suzette Delaloge, David Malka, Laurence Albiges, Patricia Pautier, Caroline Robert, David Planchard, Stéphane de Botton, François Lemare, Marilene Guillet, Vanessa Puglisi, May Abbas, Mario Di Palma, Etienne Minvielle
Journal: Journal of Clinical Oncology (2020)

2000 Background: Various interventions aiming to improve a safe use of oral anti-cancer agents have previously been reported. These retrospective studies involved nurse-led follow-up and use of health technologies. However, the potential impact of these combined strategies is limited by a lack of rigorous methodology. Methods: We performed a randomized phase 3 trial comparing an intervention combining NNs and a mobile application vs. SOC in cancer pts treated with OAA (excluding hormonal therapy) in our tertiary cancer center. Pts initiating OAA (all types of cancer, PS &lt; 3, life expectancy &gt; 6 months), were randomized in a 1:1 basis. The intervention combined a nursing-led follow-up and a mobile application for patients. NNs provided regular phone follow-ups to manage symptoms and assess toxicities, adherence and supportive care needs. Pts had access to a mobile application to record tracking data, contact NNs via secure messaging or a dedicated phone line. The intervention lasted 6 months. The primary endpoint was the Relative Dose Intensity (RDI). Secondary endpoints included adherence, toxicity, response and survival, quality of life, pts experience (PACIC Score), end-of-life support, and economic estimation of the use of healthcare resources. Results: From October 2016 to May 2019, 609 pts (median age: 62 years, 20-92; PS2: 11.8%) were included. 39% were receiving oral chemotherapy, and 61% other OAA. The RDI was significantly higher in the CAPRI arm (93.4% ±0.26 vs. 89.4% ±0.19, p = 0.04). The CAPRI intervention also improved PACIC scores (mean: 2.94±0.83 vs. 2.67±0.89, p = 0.01), the number of unplanned hospitalizations (15.1% vs. 22.0%, p = 0.04), hospitalization duration (mean: 2.82±6.96 days vs. 4.44±9.60, p = 0.02), and treatment-related grade≥3 toxicities (27.6% vs. 36.9%, p = 0.02). Conclusions: Compared to SOC, the CAPRI intervention improved RDI, pts experience, hospitalizations and their duration, as well as the rate of treatment-related grade≥3 toxicities. This type of intervention should represent a new standard in pts receiving OAA. Clinical trial information: NCT02828462.
Machine learning models to predict the response to anti-cancer therapy in metastatic melanoma patients.
Authors: Romain Goussault, Cécile Frénard, Eve Maubec, Philippe Muller, Ludovic Martin, Delphine Legoupil, Francois Aubin, Julie De Quatrebarbes, Thomas Jouary, Alice Hervieu, Laurent Machet, Emilie Varey, Philippe Lecerf, Florence Vrignaud, Amir Khammari, Brigitte Dréno
Journal: Journal of Clinical Oncology (2020)

e14071 Background: Machine learning methods are new artificial intelligence tools with promising applications in healthcare. We developed and validated 4 machine learning models to predict the response to immunotherapy and targeted therapy in stage IIIc or IV melanoma patients. Methods: This work was conducted on data from 10 centers participating in the French network for Research and Clinical Investigation on Melanoma (RIC-Mel), launched in 2012. Thus, 935 patients, corresponding to 1978 systemic treatments have been extracted from RIC-Mel database. The following data were considered: age, sex, Breslow, melanoma type, ulceration, spontaneous regression, mitotic index, number of invaded lymph nodes, extracapsular extension, mutational status, melanoma stage, number of metastasis sites, lines of treatments, and time between first melanoma excision and metastatic relapse. Treatment response: complete response, partial response, stable disease, defined as class 1 and progressive disease as class 2. We split this cohort/database into a training set (80%) and test set (20%). The algorithm performances were evaluated on the test set by the percentage of treatments correctly classified in class 1 or 2. Four machine learning algorithms (linear model, random forest, XGBoost and LightGBM) were compared in terms of performance and interpretation for both types of treatments. Results: The accuracies of the best models for immunotherapy (LightGBM) and targeted therapy (random forest) were respectively 66% and 65%. The most significant variables for building the models were respectively: stage (IIIc or IV), response to previous treatments lines, age, number of metastasis sites and time between first melanoma excision and metastatic relapse. Conclusions: We present here the first machine learning models to predict the response to immunotherapy and targeted therapy in stage IIIc or IV melanoma patients. The most predictive variables are coherent with the literature. Future development will include data from 18FDG-PET/CT imaging and other predictive markers recently identified, as circulating DNA to improve the models performance.
Quality-adjusted time without symptoms or toxicity (Q-TWiST) of lenvatinib plus everolimus versus everolimus monotherapy in patients with advanced renal cell carcinoma (RCC).
Authors: Chung-Han Lee, Yin Wan, Alan D. Smith, RAN Xie, Robert J. Motzer
Journal: Journal of Clinical Oncology (2020)

5067 Background: In the primary analysis of Study 205 phase II trial (NCT01136733), lenvatinib+everolimus (vs everolimus) significantly prolonged progression-free survival (median PFS; 14.6 vs 5.5 months, HR = 0.40, 95% CI [0.24, 0.68]) in advanced RCC patients who received one prior anti-angiogenic therapy. Overall treatment differences were evaluated in a post hoc analysis using a quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) methodology. Methods: Patients’ survival time was partitioned into three mutually exclusive health states: time spent with grade 3/4 toxicity (TOX), time prior to disease progression and without grade 3/4 toxicity (TWiST) and time post disease progression (REL). Mean time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. Non-parametric bootstrapping method was used to generate 95% CI, which evaluates the between-treatment differences. At base case, utility for TWiST, TOX and REL were assigned as 1.0, 0.5 and 0.5, respectively. A sensitivity analysis was used, applying utilities across the range of 0 (similar to death) to 1.0 (perfect health). A relative gain in Q-TWiST of ≥10% and ≥15% has been established in previous literature as clinically important and clearly clinically important, respectively. Results: Patients receiving lenvatinib+everolimus (n = 51) vs everolimus (n = 50) had significantly longer mean time in TWiST (10.9 vs 6.4 months; difference 4.5 [95% CI: 1.4, 7.8]) and numerically longer in TOX (1.9 vs 0.7 months; difference 1.2 [95% CI: -0.3, 3.1]) but shorter in REL (5.8 vs 8.5 months; difference -2.8 [95% CI: -6.2, 0.6]). At base case, lenvatinib+everolimus patients had a significant mean Q-TWiST gain of 3.7 months (14.7 vs 11.0; 95% CI of difference [1.3, 6.3]), with a relative gain of 24% vs everolimus. In a sensitivity analysis using alternative utility values for TWiST (varied from 0.55 - 0.9) with utility of TOX and REL both set as 0.5, absolute mean Q-TWiST gain ranged from 1.7 to 3.3 months, with a relative gain ranging from 11.0% to 21.2% (all significant). With TWiST utility set as 1.0 and utility of TOX and REL varying from 0 to 1.0, Q-TWiST gain ranged from 1.7 to 5.8 months (mostly significant and became non-significant as the REL utility gets closer to 1.0 and TOX utility gets closer to 0). Conclusions: Within Study 205, lenvatinib+everolimus resulted in a statistically significant and clinically important gain in Q-TWiST vs everolimus alone. Clinical trial information: NCT01136733 .
粘贴疗法在儿童面部急诊外伤中的应用
Authors: 周锐华, 张巨祥, 韩俊杰
Journal: BMJ (2008)

儿童面部外伤在急诊最为多见.由于儿童受伤后伤口出血、疼痛、紧张、恐惧,实施清创缝合手术较为困难,甚至无法在门诊治疗.我科自2003年起应用粘贴疗法治疗儿童面部急诊外伤,简单、无痛、便于操作,取得了较好的疗效。
Malignancies associated with DPP4 inhibitors and GLP1 receptor agonists: Data from a large real-world database.
Authors: Jiasheng Wang, Chang H. Kim
Journal: Journal of Clinical Oncology (2020)

1567 Background: DPP44 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1Ra) control type 2 diabetes (T2DM) by promoting GLP-1 pathway; its activation can lead to dysplasia or tumor inhibition based on tissue types. Moreover, DPP4 can act as a tumor suppressor or activator. Few studies have looked at the risk of DPP4i and GLP1Ra on various types of cancer. Methods: We inquired an aggregated electronic health record database, Explorys (IBM, NY). Patients (Pts) diagnosed with T2DM from 1/05 to 6/19 were included and followed for 5 years after starting DPP4i, GLP1Ra, or metformin. Odds ratio (OR) were calculated after 6mo of lag time. Results: We identified 344,550, 112,000, and 1,245,930 pts in the DPP4i, GLP1Ra, and metformin group, respectively. The three groups were well balanced except pts in the GLP1Ra group had higher BMI. Within 5 years, 24,260 pts (9.5%) in DPP4i, 5,580 (8.7%) in GLP1Ra, and 57,490 (9.3%) in metformin group developed any types of cancer. When adjusted for sex, age, smoking status, alcohol abuse history, hemoglobin A1C (≤9.0% vs &gt; 9.0%) and BMI ( &lt; 30 vs ≥30 kg/m 2 ) around initiation of antidiabetic agents, the aOR was 1.01 (95%CI .94-1.08) for DPP4i and 1.06 (95%CI .93-1.20) for GLP1Ra, comparing with the metformin group. For specific cancer types, DPP4i users were associated with significantly higher risk of bladder, kidney, liver cancer and melanoma; while the risk of breast, lung and prostate cancer were reduced. GLP1Ra users were associated with higher risk of thyroid cancer; while the risk of bladder, colon, lung, and prostate cancer were reduced. Conclusions: DPP4i and GLP1Ra were not associated with increased cancer risk overall. However, they were associated with increased or decreased risk of specific cancer types. [Table: see text]
Investigation of public awareness of stroke in Yangquan residents
Authors: Jin-feng Liu, Yi-shui Pan, Zhen-jiang Wang, Yu-zhen Wang, Zhi-yu Zhang, Yan-ping Zhang, Jian-fang Du, Ya-qiong Zheng, Jian-dong Zhang
Journal: BMJ (2012)

Objective We conducted a survey on the awareness rate of stroke in Yangquan residents and analyzed factors affecting awareness to provide basic information for Yangquan residents to prevent and treat stroke in Shanxi.Methods A questionnaire regarding awareness and basic knowledge of stroke was used in this study and applied to Yangquan residents.A cluster stratified sample of 7983 residents were questionnaired by cross-sectional method.Results 7921 returned copies were valid.The awareness rate of stroke in 7921 selected Yangquan residents was 30.14％ (2387/7921). Upon the occurrence of stroke,the awareness rates of the way to see a doctor,the right department to look for medical care and test manners to diagnose the illness as stroke were relatively high in these investigated people,which were 74.03％ (5864/7921),78.17％ (6192/7921) and 84.04％ (6657/7921),respectively.However,the number of people who knew characteristic symptoms and complications of stoke,risk factors that cause stroke and how to treat stroke was 2021 (25.51％),841 ( 10.62％ ),and 902 ( 11.39％ ),respectively,which was relatively low. After multivariate analysis,the awareness rate of stroke in Yangquan residents was positively correlated with an education degree.Conclusions Yangquan residents know little about stroke.Therefore,it is necessary to increase the level of their knowledge regarding stroke by extended propaganda and encourage them to live a healthy life to be able to treat stoke in time and to reduce the possibility of stroke occurring.

Key words: 
Cerebrovascular accident; Health knowledge, attitudes,practice; Questionnaires