tbuckley/cabot-search huggingface dataset:
MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients.
Authors: Fatima Cardoso, Laura van 't Veer, Coralie Poncet, Josephine Lopes Cardozo, Suzette Delaloge, Jean-Yves Pierga, Peter Vuylsteke, Etienne Brain, Giuseppe Viale, Sherko Kuemmel, Isabel T. Rubio, Gabriele Zoppoli, Alastair Mark Thompson, Erika Matos, Khalil Zaman, Florentine Hilbers, Aleksandra Dudek-Perić, Bart Meulemans, Martine J. Piccart-Gebhart, Emiel J. Rutgers
Journal: Journal of Clinical Oncology (2020)

506 Background: The 70-gene signature MammaPrint has been shown to identify breast cancer patients for whom adjuvant chemotherapy (CT) could be safely omitted even in the presence of unfavorable standard clinical-pathological criteria. The MINDACT primary endpoint at 5 years median follow-up was met in 2016 (Cardoso et al, NEJM 2016) with a distant metastasis free survival (DMFS) rate at 5 years of 94.7% (95% CI: 92.5-96.2) in clinical high (C-High) / genomic low (G-Low) risk patients who received no CT. Longer follow-up is now available. Methods: 6693 patients were enrolled in the prospective phase III randomized MINDACT study (EORTC 10041/BIG3-04) between 2007-2011. We assessed the DMFS rate at 5 years in the primary test (PT) population of C-High / G-Low patients who were randomized to receive no CT (n = 644). As secondary analysis, we evaluated DMFS and overall survival (OS) in the intention to treat (ITT) population of the C-High / G-Low group randomized to CT vs no CT (n = 749 and 748 respectively). Comparisons between CT and no CT groups are low-powered. We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% CI from cox-regression models adjusted for stratification factors used for the randomization. Results: The median follow-up is 8.7 years, resulting in an updated 5-year DMFS rate for the PT population of C-High / G-Low patients with no CT of 95.1% (95% CI 93.1-96.6). The updated outcomes of the ITT population of C-High / G-Low patients are shown in the table. Further analyses will update the suggested age-dependent effect of CT omission for luminal breast cancer seen at 5 years in pre- versus post-menopausal women as in Tailor-X (Piccart et al, SABCS 2019). Conclusions: The primary DMFS endpoint at 5 years continues to be met in CT untreated C-High / G-Low risk women, confirming MINDACT as a positive de-escalation study. With longer follow-up and in line with the natural history of luminal breast cancer, more distant relapses do occur but the estimated gain of 2.6% for CT administration in C-High / G-Low patients remains small in light of CT harmful effects. The level IA evidence for the clinical utility of the 70-gene signature for adjuvant CT decision making is maintained. Clinical trial information: NCT00433589 . [Table: see text]
MIRASOL (GOG 3045/ENGOT OV-55): A randomized, open-label, phase III study of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression.
Authors: Kathleen N. Moore, Toon Van Gorp, Jiuzhou Wang, Brooke Esteves, Patrick A Zweidler-McKay
Journal: Journal of Clinical Oncology (2020)

TPS6103 Background: Elevated FRα expression is a characteristic of several solid tumors, including epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has shown consistent and meaningful single agent clinical activity, along with favorable tolerability, in patients with high FRα expressing tumors. Methods: MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of high FRα positivity by immunohistochemistry (high expression; ≥ 75% of cells with PS2+ staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival (PFS; by investigator) and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL opened for enrollment in December 2019. Clinical trial information: NCT04209855.
Vitiligo is correlated with clinical benefits in patients with advanced cutaneous melanoma treated with immune checkpoint inhibitors (ICI).
Authors: Gaston Martin Reinas, Marcelo Muino, Mariana Abal, Carlos Garcia Gerardi, Flavio Tognelli, Ernesto Gil Deza, Cesar Gonzalez, Liliana D Gonzalez, Marcelo Andres Nunell, Alba Marin Ordoñez, Eduardo L. Morgenfeld, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2020)

e22023 Background: Use of ICI changed the treatment of Advanced Cutaneous Melanoma Patients (ACMP). This paper analyzes the evolution of ACMP who develop vitiligo during ICI treatment at Instituto Oncológico Henry Moore (IOHM). Methods: We selected all ACMP that received ICI between August 2015 and December 2019. We collected clinical data and compared Group A (ACMP with vitiligo) with Group B (ACMP without vitiligo) on: response rate (RR), time from ICI treatment initiation to progression (TTP) and overall survival (OS), defined as time from ICI treatment initiation to death. Outcomes were assessed using table tests and Kaplan-Meier curves with log-rank test. Results: Out of 32 ACMP treated with ICI, 12 Pt (37%) were in Group A and 20 Pt (63%) were in Group B. Table shows group characteristics and outcomes. Conclusions: 1) During treatment with ICI, 12 out of 32 (37%) advanced cutaneous melanoma patients were afflicted with vitiligo. 2) Two out of three patients who responded to ICI treatment developed vitiligo and obtained better TTP and OS than those without vitiligo. 3) According to these results, vitiligo is the consequence of the immune system reactivation responsible for considerable clinical benefits. Further studies should analyze if it is feasible to reduce ICI doses in patients who develop this adverse effect. 4) In this small and retrospective series, Nivolumab was more frequently correlated with vitiligo and clinical benefits, but we need prospective studies to decide which ICI treatment is the most effective. [Table: see text]
肺癌伴甲胎蛋白强阳性一例
Authors: 易正明, 刘建超
Journal: BMJ (2005)

患者男,64岁.因体检发现肝、肺肿块,甲胎蛋白(AFP)强阳性,为明确诊断入院检查.2003年11月17日患者体检中,B超发现肝脏有多发性肝囊肿样病变,最大9 cm;胸透见右侧胸膜腔积液、右肺上叶可疑肿块和胸膜腔上部多个半圆形组织影像物.实验室检查:HBsAg、HBeAb、HBcAb均阳性,肝功能正常,AFP 1 210 ng/ml(参考值<8 ng/ml).既往史:1975年B超检查见肝多发性囊肿,最大4 cm,以后多次B超复查见肝囊肿逐渐增大,但无肝区不适而未作处理;2002年10月因阳萎发现双侧睾丸逐渐缩小,左侧仅鸽蛋大小,会阴部潮湿。
Abstract 114: Downregulation of Small GTPase Rnd3 in Cardiomyocytes Leads to Hyperinflammatory Response in Post-myocardial Infarction Heart
Authors: Yuan Dai, Xiangsheng Yang, Xiaojing Yue, Tingli Yang, Xin Yi, Xi Lin, Fei Wang, Jiang Chang
Journal: Circulation Research (2016)

Background: Hyperinflammatory response leads to maladaptive healing and remodeling after acute myocardial infarction (MI), while a balanced inflammatory response is essential for post-MI repair and remodeling. Most of the studies have focused on inflammatory cells, extracellular matrices and myofibroblasts in the regulation of acute MI-induced inflammatory response, the investigation of crucial role of cardiomyocytes in the initiation and regulation of the responsive inflammation in heart has been overlooked. Subjects and Methods: To demonstrate that small G protein Rnd3 functions as a negative regulator to refine the inflammatory response by preventing excessive inflammation in cardiomyocytes after acute MI. Genetic mouse models with cardiomyocyte-specific knockout and overexpression of Rnd3 were studied along with multiple cell culture approaches. An acute MI was introduced by ligation of the left anterior descending artery. Results: Mice with cardiomyocyte-specific deletion of Rnd3 (heterozygous, Rnd3 +/- ) showed a significantly higher mortality, worse cardiac function, and increased infarct size compared to wild-type control mice after MI. Massive inflammatory cell infiltration along with a profound increase in the expression levels of cytokines, MMP2 and MMP9 were observed in the infarcted and remote areas in Rnd3 +/- heart. Mechanistic studies revealed that Rnd3 bound to NFκB complex and attenuated NFκB activity by 1) physically interacting with NFκB component p65; 2) competing with NFκB component p50 for p65 binding; 3) blocking p65 nuclear import. The mechanisms were demonstrated in vitro and in vivo . Cardiomyocyte-specific overexpression of Rnd3 in mice inhibited hyperactivation of NFκB signaling, attenuated excessive inflammatory response, reduced infarct areas and ameliorated post-MI cardiac function. Conclusions: 1) This study demonstrates cardiomyocytes as an intrinsic and crucial component in the initiation of the inflammatory cascade in acute MI; 2) discover Rnd3 as a new “fine-tuning” factor situated at the nexus of the inflammatory response; 3) reveal a novel molecular mechanism through Rnd3-mediated NFκB signaling axes responsible for a balanced inflammatory response after acute MI.
Application of parametric image processing of contrast-enhanced ultrasound imaging in diagnosis of ovarian masses
Authors: Lu Chen, Li Hong, Min Hu, De-bin Wu, Xue-jiao Zhu, Qing Sun, Wen-ying Wu
Journal: BMJ (2011)

Objective To investigate application value of parametric image processing in contrastenhanced ultrasound imaging in diagnosis of ovarian masses. MethodsFifty cases with ovarian masses underwent routine ultrasound and contrast-enhanced ultrasound imaging using a new dedicated parametric image processing software SonoLiver to analyze patterns of vascular formation and blood stream perfusion in the ovarian mass tissues on a digital video recorder in real time, compare their morphological characteristics of time-intensity curve (TIC) and dynamic vascular patterns (DVP) curve, and analyze quantitatively all indicators generated by SonoLiver. ResultsIn ultrasound imaging of the 50 cases, there were 24 cases (86％) displaying mainly blue lowly-enhanced imaging in those with benign masses and 15 cases (68％)displaying mainly red highly-enhanced imaging in those with malignant masses, with statistical significance (P ＜0. 01 ). There was significantly different characteristics of TIC and DVP between patients with benign and malignant masses. In 23 cases with benign masses, their DVP were significantly higher above the baseline than in those with malignant ones ( P = 0. 000), and in 15 cases with malignant lesions, their DVP were much shorter below the baseline than in those with benign ones, with statistical significance (P ＜0.05). The intensity of contrast medium, the time to reach its peak intensity and average transit time were all significantly higher in those with malignant masses than in those with benign ones (all P ＜ 0. 05 ). But, no statistical difference in the time of initial increasing between the two groups was found (P ＞ 0. 05). Conclusions There is significant difference in TIC and DVP of ultrasound imaging between benign and malignant masses, which if combined with contrast enhanced ultrasound parametric image processing can provide a more visualized quantitative information of benign and malignant ovarian masses with SonoLiver software.

Key words: 
Ovarian neoplasms;  Ultrasonography interventional;  Diagnosis
Characterization of clonal hematopoiesis of indeterminate potential mutations from germline whole exome sequencing data.
Authors: Hsin-Ta Wu, Ekaterina Kalashnikova, Samay Mehta, Raheleh Salari, Himanshu Sethi, Bernhard Zimmermann, Paul R. Billings, Alexey Aleshin
Journal: Journal of Clinical Oncology (2020)

1525 Background: Clonal hematopoiesis of Indeterminate Potential (CHIP) is an age-related phenomenon where somatic mutations accumulate in cells of the blood or bone marrow. It is a source of biological noise that causes false-positives in ctDNA analysis and is present in up to 20% of individuals over the age of 70. The presence of CHIP has been linked to an increased risk of hematologic cancers and cardiovascular disease. The Signatera assay filters CHIP mutations through tumor tissue and germline sequencing thereby reducing false-positive results and focuses on tumor-specific mutations for each patient. Methods: Whole exome sequencing data (average depth ~250x) analyzed from patients’ buffy coat (n = 159) was used to characterize CHIP mutations. Variant calling was performed using Freebayes variant caller with allele frequency threshold between 1% and 10%. Following which variant annotation and selection was performed based on the top 54 genes that are most implicated in myeloid disorders. The selected variants were further screened based on the reported variants in the literature and/or the Catalog of Somatic Mutations in Cancer (COSMIC). Results: The analysis revealed an average of 0.14 (0-2) CHIP mutations per patient with an average variant allele frequency of 3.49% (1%-8.5%). The most common CHIP mutations were observed in DNMT3A, (n = 17), TET2 (n = 7) and TP53 (n = 7) genes. The percentage of patients with at least 1 mutation found in DNMT3A, TET2, and TP53 were 4.2%, 1.94%, and 1.38%, respectively. Other genes containing CHIP mutation included CEBPA, ETV6, HRAS, PDGFRA, NRAS, KMT2A, EZH2, GATA2, GNAS at a frequency below 1%. CHIP mutations were not observed in patients younger than 40 years, but they increased in frequency with every decade of life thereafter. The incidence of CHIP increased from 0.04 for the 40-50 yrs age group to 0.18 for individuals older than 60. Further analysis of associations between incidence of CHIP and cancer type, prior exposure to chemotherapy as well as longitudinal evolution of CHIP mutations during cytotoxic treatment are underway and will be presented. Conclusions: CHIP, a common finding in the elderly population is an important factor to consider in ctDNA analysis and most frequently involves DNMT3A, TET2, and TP53 genes. The frequency of CHIP can be impacted by a number of other factors such as cytotoxic chemo- or radiotherapy.
心理咨询方法在综合医院精神心理障碍患者中的应用
Authors: 陈文姬
Journal: BMJ (2011)

综合医院或社区卫生服务中心常常有精神心理障碍的患者,以各种躯体不适反复就医而不会主动寻求心理帮助.全科医牛应掌握心理咨询的方法引导此类患者配合治疗.笔者在实践中将中医学原理与认知行为疗法、认识领悟疗法相结合,根据不同患者予以灵活应用.现就方法和体会介绍如下。
Effect of expression of ICOS in cutaneous T-cell lymphoma and its targeting on killing of malignant cells.
Authors: Florent Amatore, Nicolas Ortonne, Marc Lopez, Florence Orlanducci, Rémy Castellano, Saskia Ingen-Housz-Oro, Amandine Decroos, Laurent Gorvel, Armelle Goubard, Reda Bouabdallah, Nathalie Bonnet, Jean-Jacques Grob, Philippe Gaulard, Martine Bagot, Armand Bensussan, Philippe Berbis, Daniel Olive
Journal: Journal of Clinical Oncology (2020)

e20040 Background: Advanced stage cutaneous T-cell lymphomas (CTCLs) remain an unmet medical need. Immunomodulatory agents such as mogamulizumab, anti-KIR3DL2 and brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate (ADC) coupled to monomethyl-auristatin-E (MMAE), provided encouraging results but new targeted therapies are needed. Inducible Co-Stimulator (ICOS), a T-cell costimulatory receptor involved in the development of CTCLs, arouses interest. Methods: We used immunohistochemistry to study ICOS expression in skin biopsies of 23 patients with early-stage mycosis fungoides (MF), 12 with transformed MF (TMF) and 17 with Sézary Syndrome (SS), at diagnosis or in relapse. ICOS expression by circulating Sézary cells and regulatory T cells (Tregs) in patients with SS was evaluated using flow cytometry, and compared to healthy donors (HD) lymphocytes. In 5 patients with SS, we also analyzed concomitant biopsies from involved nodes. Then, we investigated the efficacy of anti-ICOS ADCs generated by coupling murine anti-ICOS monoclonal antibodies with MMAE, in comparison to BV. We used ICOS + CTCL cell lines (MyLa and MJ), murine xenograft models with MyLa and ICOS + Patient Derived Xenografts (PDXs) from patients with SS and angioimmunoblastic T-cell lymphoma (AITL). Results: ICOS was highly expressed by the cutaneous atypical lymphocytic infiltrates in respectively 61%, 75% and 88% of patients with early-stage MF, TMF and SS, such as in the 5 patients with node involvement. ICOS expression by circulating Sézary cells was strong: 69±7.3% versus 38.8±7.1% of non-tumoral CD4 + cells ( p&lt; 0.009; CI95%: 8.7-51.6); and 31±3.2% of CD4+ cells in HD ( p&lt; 0.0001; CI95%:20.3-46.3). Percentages of ICOS + Tregs were significantly higher in patients with SS than in HD. In CTCL cell lines, we observed a significant dose-dependent decrease in cell viability in the presence of anti-ICOS ADCs. In a mouse xenograft model (MyLa), anti-ICOS ADCs provided a longer overall survival (OS) than BV (HR = 15.2;CI95%:3.2-71.1; p&lt; 0.0006). Finally, in ICOS + PDXs anti-ICOS ADCs significantly improved OS, and reduced the number of tumor cells in the blood, bone marrow and spleen. No evidence of ADC toxicity was observed in treated mice. Conclusions: All together our results show that ICOS is a therapeutic target of interest in CTCLs and provide the preliminary basis for a therapeutic trial
社区老年糖耐量异常患者180例心理健康状态的调查
Authors: 查松柏, 钟志廷
Journal: BMJ (2006)

有多项研究证实,心理社会因素、社会支持及患者的个性特征在其发病及血糖水平的控制中起着重要作用.本研究对经过筛选确诊为糖耐量异常(IGT)的180例患者,应用症状自评量表(SCL-90量表)和汉密尔顿焦虑量表(HAMA量表)进行心理状态调查,现将调查结果报告如下。
Resting memory CD4+ T cells and plasma cells in gastric cancer may be potential immune biomarkers.
Authors: Jingde Chen, Bei Zhang, Yifan Zhou, Xiaochen Zhao, Yuezong Bai
Journal: Journal of Clinical Oncology (2020)

e16523 Background: Previous studies revealed the CD8+T cells deeply involved in tumor progress and reaction to immunotherapy. Now we used expression data and in silicon algorithm to analyze immune cell composition in gastric cancer and explored other subsets of immune cells that may be the potential immune biomarkers. Methods: CIBERSORT quantified 22 immune cell subtypes using four GEO gastric cancer cohorts (GSE15459, GSE26253, GSE29272, GSE57303) and TCGA-STAD, TCGA-PAAD gene expression data, and only CIBERSORT P- value of &lt; 0.05 were included in the survival analysis. Immune cell high was defined as ≥median cells proportion individually and were computed for survival analysis and hazard ratios. Wilcox test was applied to analyze the differences between normal and tumor tissues. Log-rank Mantel-Cox test was applied to compare the survival curves between the patient groups. Statistical analyses were conducted using R v3.3.2. Results: Unsupervised hierarchical analysis of four GEO gastric tumor cohort using 22 immune cells proportions identifies three subclasses. In the subclass with the best overall survival performance, we found enriched resting CD4 T memory cells. Then in TCGA-STAD (P = 0.03) and TCGA-PAAD (P = 0.03) cohort, we observed that normal tissue obtained higher fraction of resting CD4 T memory cells than tumor. On the other hand, in patients who administrated chemotherapy in TCGA-STAD, by comparing immune cell high and low subgroup, we found that plasma cells (P = 0.02), T cells CD8(P = 0.03) were associated with improved overall survival. while, neutrophils(P = 0.05), NK cells resting(P = 0.04), were correlated with decreased overall survival. Also we proved one similar result in GEO cohort, that plasma cells-high (above median) subgroup provided increased overall survival (P = 0.04, HR = 0.76). In contrast, other three immune cells were not significantly associated with survival benefits. Conclusions: Together, these results indicated that memory CD4 T cells and plasma cells infiltration in gastric cancer have important clinical meanings and may be potential immune biomarkers. The continued integration of observations from a variety of experimental models will be required to further understand and utilize the full potential of immune cells.
Symptomatic characteristics and factors related to severity of irritable bowel syndrome
Authors: Wenjuan Fan, Min Chang, Xiaoqing Li, Liming Zhu, Guijun Fei
Journal: BMJ (2017)

Objective
To analyze symptomatic characteristics and the factors related to severity of irritable bowel syndrome (IBS).


Methods
Total 516 IBS patients met Rome Ⅲ criteria were enrolled in the study from June 2009 to February 2016.A questionnaire survey was conducted in face-to-face manner, including intestinal and extra-intestinal symptoms, sleeping and psychological status.Severity of IBS was determined by symptom scores.


Results
Among 516 patients, there were 135 cases with mild symptoms (26.2%), 267 with moderate symptoms (51.7%) and 114 with severe symptoms (22.1%). Periumbilical pain/discomfort associated with defecation was a common symptom location (34.6%, 178/516), however, 53.3% (275/516) patients also reported having abdominal pain/discomfort during non-defecation period.In IBS patients, 51.2% (264/516) were coexisted with gastroesophageal reflux disease (GERD), 59.1% (305/516) with functional dyspepsia (FD), and 46.9% (242/516) with depression.The prevalence of ordinary abdominal pain/discomfort[57.0%(217/381) vs. 43.0%(58/135), χ2=7.841], sensation of incomplete defecation[74.5%(284/381)vs. 61.5%(83/135), χ2=8.277] and coexisted GERD[54.1%(206/381) vs. 43.0%(58/135), χ2=4.920], FD[64.0%(244/381)vs. 45.2%(61/135), χ2=14.664], headache[50.7%(193/381)vs. 38.5%(52/135), χ2=5.889] and depression[52.2%(199/381)vs. 31.9%(43/135), χ2=16.623] in patients with moderate to severe symptoms were significantly higher than that in patients with mild symptoms(all P<0.05). The predictors to moderate-severe IBS symptoms were coexisted FD (OR=1.798, 95%CI: 1.162-2.783, P=0.010) and depression (OR=1.696, 95%CI: 1.043-2.759, P=0.014).


Conclusion
The symptoms of IBS patients are various, and patients coexisted with FD and depression are more likely to have more severe symptoms.


Key words: 
Irritable bowel syndrome; Severity of illness index; Comorbidity