tbuckley/cabot-search huggingface dataset:
The genomic profile and potential predictive circulating cytokines of gastric cancer combine disseminated intravascular coagulation.
Authors: Jian Xiao, Shanshan Li, Xiaohui Zhai, Xinyi Liu, Yaoxu Chen, Mengli Huang
Journal: Journal of Clinical Oncology (2020)

e16543 Background: Advanced gastric cancer (GC) combined with disseminated intravascular coagulation (DIC) is a rare clinical disease, but disease progression was rapid and the prognosis is extremely poor. Therefore, an effective whole-course treatment scheme is urgently needed, and the understanding of the molecular mechanism of the disease is still a blank. Methods: FFPE tissues were collected from 8 DIC and 62 non-DIC Chinese gastric cancers. Whole-exome sequencing (WES) by NGS technology was performed on the tissue samples. We also evaluate the protein level of circulating cytokine among 5 DIC GC and 15 non-DIC GC from the preoperative blood specimens by ELISA detection. Results: More than 700 genes related to cancer were addressed specifically. The most frequent mutated genes in DIC GC group are different from non-DIC GC group. 75% (6/8) DIC GC were detected to harbor AR gene mutations. NCOR2 (50%, 4/8) and KMT2C (37.5%, 3/8) were also most frequent mutated genes. While TP53 (72.6%, 45/62), APC (43.5%, 27/62) and KRAS (38.7%, 24/62) were the most frequent mutated genes in non-DIC gastric cancers. As an exotic comparison, the WES data from the public TCGA-STAD (n = 544) cohort was analyzed. The most frequent mutated genes turned out to be TP53 (45.1%, 205/455), LRP1B (28.6%, 130/455) and ARID1A (24.6%, 112/455). For ELISA detection, protein levels of MIP-1α (p = 0.0311)、IL-8 (p = 0.0435)、TNF-α (p = 0.0339) and MCP-1 (p = 0.0187) were significantly lower in DIC GC group, respectively, as compared to non-DIC GC group. In accordance with result of WES, 60% (12/20) samples in non-DIC GC group had more than one gene variation related to immune activation, while 25% (2/8) samples in DIC GC group had only one gene variation. Conclusions: Our study showed that DIC gastric cancers had unique molecular characteristics. Their development may be driven by malfunction in steroid hormone receptors activation other than TP53. DIC GC harbored less DNA variations than non-DIC GC. Circulating cytokine, such as MIP-1α、IL-8、TNF-α and MCP-1, may be served as potential monitoring indicators in the acute phase of DIC GC patients
Performance of time to discontinuation and time to next treatment as proxy measures of progression-free survival, overall and by treatment group.
Authors: Mark S. Walker, Lisa Herms, Paul J.E. Miller
Journal: Journal of Clinical Oncology (2020)

e19135 Background: Real-world data sources have historically provided limited information about the occurrence of disease progression. As a result, progression-free survival (PFS), a standard effectiveness outcome measure in oncology, has been estimated using proxies such as time-to-discontinuation (TTD) or time-to-next-treatment (TTNT). Curation of unstructured electronic medical record (EMR) data make it possible to calculate PFS from directly observed progression. The aim of this research was to compare TTD and TTNT as proxy indicators with PFS determined from direct statements regarding progression in the medical record and to compare effect sizes on treatment-based groups across these endpoints. This report cites findings from the metastatic breast cancer (mBC) setting. Methods: Previously curated EMR data were collected from Concerto’s Definitive Oncology Dataset for adult, female, hormone receptor-positive/human epidermal growth factor receptor-negative mBC patients diagnosed 2008 or later who received at least one line of systemic therapy. Patients were grouped based on any receipt vs. no receipt of an aromatase inhibitor (AI) in first line (1L). Kaplan-Meier and Cox regression methods were used to calculate PFS, TTD, and TTNT in 1L and OS from start of 1L. Results: The study included 378 patients, of which 138 (36.5%) were de novo stage IV or metastatic. The mean patient age was 60.3 years (SD 13.3), 57.1% were Caucasian, and 68.3% were postmenopausal. Conclusions: Estimates of TTD and TTNT aligned closely, suggesting that nearly all patients who discontinued initial therapy received subsequent treatment. Notably, TTNT and TTD were both meaningfully shorter than PFS, suggesting that their use as proxy indicators may systematically underestimate PFS. Further, analysis based on receipt of AI indicates that comparative effects on TTD or TTNT may produce quite different results than those for PFS and OS. [Table: see text]
Observation of the foramen of Monro on magnetic resonance imaging and its clinical significance
Authors: 蔡强, 袁先厚, 刘昌盛, 阳朝晖, 陈谦学, 刘仁忠, 史强, 陈治标, 黄书岚, 叶应湖, 王国安
Journal: BMJ (2007)

目的 探讨室间孔的影像定位及其临床意义.方法 对30例正常人头颅磁共振成像的室间孔进行观察,了解其位置、形态及大小;同时与脑积水及室间孔区域肿瘤患者的室间孔进行比较.结果 室间孔位于大脑内侧、丘脑前端和穹窿之间,平均横径为2.8 mm,纵径为2.1 mm,双侧室间孔与第三脑室间形成一Y形结构.脑积水患者室间孔形态及大小变化非常明显,有时与第三脑室和侧脑室融为一体,形成兔头征.室间孔区域肿瘤患者室间孔因肿瘤位置和大小的不同而表现不一.结论 室间孔在颅内的位置相对恒定,其位置、大小和形态的改变是颅内病变的重要征象;手术前应根据个体化的原则测量其大小及位置以决定手术的方案。
胰腺腺泡细胞癌肝转移误诊为包虫病一例
Authors: 丛振杰, 林琳, 肖大伟
Journal: BMJ (2006)

患者女,40岁,1个月前无明显诱因出现上腹部疼痛不适,呈持续性钝痛,阵发性加重,无恶心、呕吐及腹泻、黑便,无胸闷、发热.全身皮肤黏膜无黄染、水肿、皮疹及蜘蛛痣等.腹部平坦,未见肠型及蠕动波,肝脾未及,全腹无压痛,移动性浊音阴性,未及包块.全身浅表淋巴结未及肿大.肝包虫皮试阴性.包虫酶标试验阴性.实验室检查:癌胚抗原(CEA)700 ng /L(0～8 000 ng /L),CA19-9 600 U/L (100～37 000 U/L),CA125 11 130 U/L(100～35 000 U/L),肿瘤多肽抗原(TPA) 3 100 ng/L(0～1 000 ng/L),肿瘤生长因子(TSGF)47 500 U/L(0～64 000 U/L),红细胞沉降率(ESR)13 mm/1 h,血常规白细胞(WBC)5.44×10.9/L。
Doctors, patients, and the drug industry: Partners, friends, or foes?
Authors: Coutts Gordon
Journal: BMJ (2009)

药品企业、学者、医疗专家和患者之间的关系一直以来都不被人看好，这些群体都希望能改善彼此间的关系。皇家外科学院本周提出了42条建议，旨在促进各方和药品企业建立更有成效的关系。这里我们列出有关药品企业和医生与患者之间应该具有什么理想关系的5种观点以及需要采取的相应措施。
Correlation study between complement C3 level and degree of disease activity in patients with systemic lupus erythematosus
Authors: Zhang Xiaoli, Xu Shengqian, Cai Jing, Chen Shanyu, Xu Jianhua
Journal: BMJ (2016)

Objective
To investigate the relationship between complement C3 level and the degree of disease activity in patients with systemic lupus erythematosus(SLE).


Methods
A total of 1 012 patients with SLE were enrolled in this study from January 2006 to December 2013 at department of rheumatology and immunology, the first affiliated hospital of Anhui medical university. Serum complement C3 level was detected by rate erythenephelometry assay. The relationship between reduction of complement C3 and SLE was analyzed.


Results
Serum complement C3 clearly decreased in 782 patients, accounted for 77.27%. There were significant differences concerning serum complement C3 level among different groups of disease activity (F=131.275, P<0.01). The low serum complement C3 level was correlated with the high degree of disease activity (r=-0.517, P<0.01). Patients with SLE had a severe disease activity (SLE disease activity index ≥15) when the level of serum complement C3 was less than 0.57 g/L. Serum complement C3 levels were positively correlated with serum complement C4 (r=0.845, P<0.01), peripheral blood leukocyte count (r=0.115, P<0.01), hemoglobin (r=0.069, P<0.01), platelet count (r=0.177, P<0.01) and albumin level (r=0.091, P<0.01). There was also a negative association of serum complement C3 with 24 h urinary protein (r=-0.228, P<0.01). 101 patients whose average level of serum complement C3 was(0.48±0.26)g/L, were treated with glucocorticoid pulse therapy as high degree of disease activity.


Conclusions
There is a close relationship between serum complement C3 level and the degree of disease activity in SLE. Serum complement C3 less than 0.57 g/L might be seen in SLE with severe disease activity.


Key words: 
Lupus erythematosus, systemic; Complement system proteins; Disease activity
Efficacy and safety of PEGylated recombinant human granulocyte stimulating factor in the prevention of neutropenia during concurrent chemoradiotherapy.
Authors: Dongling Zou, Qi Zhou, Mingfang Guo
Journal: Journal of Clinical Oncology (2020)

e18018 Background: This randomized controlled prospective study aims to explore the efficacy and safety of using PEG-rhG-CSF to prevent neutropenia during concurrent chemoradiotherapy of paclitaxel and cisplatin (TP) regimen for cervical cancer. Methods: Patients who met the eligibility criteria were divided into two groups according to the randomized principle of 2:1: the experimental group (patients used 6 mg PEG-rhG-CSF prophylactically after chemotherapy) and the control group (patients did not use PEG-rhG-CSF for prevention and were given 5 ug / kg rhG-CSF when ANC &lt; 1✕10 9 ). TP combination regimen was used for concurrent chemotherapy, specifically as follows: paclitaxel 150mg / m 2 (day 1), cisplatin 35mg / m 2 (day 1-2), repeated every three weeks. The PTV dose was 45 Gy in 1.8 Gy daily fractions, with five fractions per week. SPSS 25.0 software was used for statistical analysis of the data, t-test was used for measurement data, and χ2 test Fisher exact test was used for enumeration data. P &lt; 0.05 was considered statistically significant. Results: As of September 2019, 30 patients were enrolled into this study, including 18 in the experimental group and 12 in the control group. One of the 18 patients in the test group (5.6%) had a Grade 3/4 neutropenia. Ten of the 12 patients in the control group (83.3%) developed Grade 3/4 neutropenia. The incidence of Grade 3/4 neutropenia in the two groups was statistically significant (P &lt; 0.001, Table 1). The incidence of FN was 5.6% in the experimental group and 8.3% in the control group (P = 1.000). The incidence of delayed chemotherapy course was 11.1% in the experimental group and 58.3% in the control group (P = 0.013). The incidence of delayed chemotherapy course in the two groups was statistically significant (Table 1). As shown in Figure 4, the experimental group had a completion time of radiotherapy for 46.7 days, while the control group had 49.0 days (P = 0.278). Conclusions: Although the results of bone marrow function and overall survival are still to be obtained, it can be initially seen from the intermediate-term data that the use of PEG-rhG-CSF primary prevention reduced the granulocytopenia and the delay of the chemotherapy course during the concurrent chemoradiotherapy TP regimen for cervical cancer, which has the value of further completing this study. [Table: see text]
Association of intraoperative opioids with improved recurrence-free survival in triple-negative breast cancer.
Authors: Giacomo Montagna, Margaret L Hannum, Kay See Tan, George Plitas, Patrick J. McCormick, Gregory W Fischer, Monica Morrow, Joshua S Mincer
Journal: Journal of Clinical Oncology (2020)

542 Background: Opioid-induced immunomodulation may be of particular importance in triple negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and outcomes in a large TNBC cohort. Methods: Consecutive patients with stage I-III primary TNBC treated between 03/2010 and 12/2016 were identified from our prospectively maintained database. Total intraoperative opioid dose was extracted from anesthetic records and converted to oral morphine milligram equivalents (MME) (10 MME = 50 mcg fentanyl IV). Univariable and multivariable (MVA) Cox proportional hazards analysis (adjusting for relevant clinicopathological features, (neo)adjuvant therapy, anesthesia technique and morbidity score), were performed to quantify the association between opioid exposure and recurrence-free survival (RFS) and overall survival (OS). Results: 1143 patients were included. Median age was 54 years (IQR 45, 64). 911 (80%) had ductal histology, 359 (31%) had nodal metastases, and 1070 (94%) were poorly differentiated. 781 (68%) received adjuvant chemotherapy and 313 (27%) received neoadjuvant chemotherapy. 525 (46%) received total intravenous anesthesia and 618 (54%) had general anesthesia. Median intraoperative opioid dose was 30 MME (IQR 20, 60). 5-year RFS was 81% (95% CI 79%-84%), 5-year OS was 86% (95% CI 84%-88%). In MVA, higher opioid administration was associated with favorable RFS but did not significantly affect OS (Table). Conclusions: Our study is the first to directly evaluate intraoperative opioid administration in TNBC and suggests a protective effect on RFS. Future work will focus on elucidating the underlying mechanism for this effect, including possible modulation of endogenous opioid signaling pathways and immunologic correlates. [Table: see text]
Survival impact of metastasis surgical resections and sidedness of primary (1º) tumor location in metastatic colorectal cancer (mCRC) without monoclonal antibodies: Retrospective review from 2003 through 2019.
Authors: Marcos André Marques Portella, Mariana Paula Cunha Gonçalves, Munir Murad Junior, Robson dos Santos Borges, Ana Livia Alves Preisser, Junia Brunelli Cassétte Azevedo, Amandio S. Fernandes, Roberto Porto Fonseca
Journal: Journal of Clinical Oncology (2020)

e16022 Background: Recent data demonstrated a median overall survival (OS) about 35 months for patients with mCRC based on the use of monoclonal antibodies (MA), anti-VEGFR and / or anti EGFR, with sidedness of primary tumor as an independent prognostic marker. However the influence of surgical resections of metastases has not yet been quantified especially after 2003 when were attributed to the inclusion of MA (Kopetz et al 2009). We hypothesized the impact of metastatectomy rate (MR) in the OS of a population without MA and their influence on primary tumor location. Methods: Data from 291 consecutive patients diagnosed with mCRC treated in a clinical center in Brazil, from 2003 to 2019, without MA. 1° location was determined by chart review: R-sided = cecum to hepatic flexure; L-sided = splenic flexure to rectum. Pts with transverse tumors were excluded. Survival from diagnosis was calculated via kaplan-Meier and compare between the right and the left side has estimated via Cox Regression. Results: 50.85%(148) of patients had a primary tumor in the left colon. Oxaliplatin was used in 1° line in 85 % and irinotecan in 75% in 2° line, most of the metastasis was metachronous, only to a single-organ (50,9% liver, 18% lung) and 40 % underwent resection at the diagnosis. The overall survival for the entire cohort was 34.1 months (95% CI, 28.9 to 45.4 months) with 39 % MR. Sidedness (R vs L) had interaction with resected and non-resected metastasis p &lt; 0.001). See OS Table results by sidedness below. Conclusions: It was possible to infer that the metastasectomy rate still have a significant and isolated benefit in the OS of this cohort without the use of MA, regardless of the mutational status of the tumors, being influenced by the sidedness of the primary tumor in the analyzed outcomes. [Table: see text]
Predictive and prognostic factors of apatinib in metastatic colorectal cancer.
Authors: Fen Wang, Shubin Wang, Xia Yuan, Jun Jia, Xiaoxia Bi, Zeqiang Zhou, Qiming Zhou, Xia Li, Changguo Luo, Minghui Deng, Liangjie Yi, Yong Li, Jianxin Lu, Wenzhi Su, Hanbin Chen, Yu Zhu
Journal: Journal of Clinical Oncology (2020)

e16092 Background: It has been extremely challenging to identify suitable predictive or prognostic factors of anti-VEGF agents. Apatinib, a vascular endothelial growth factor receptor 2(VEGFR-2) inhibitor, showed promising efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients in a phase II trial. The aim of current study was to identify the potential predictive and prognostic factors of apatinib in this phase II trial. Methods: A total of 48 patients with mCRC who had failed from standard fluorouracil-containing chemotherapies were recruited in this prospective single-arm study. Apatinib at a 500mg dose was administered daily continuously. Clinical parameters, including patients background, biochemical parameters at baseline, tumor markers at baseline and day 28, and adverse events in initial 28 days were evaluated to identify predictive and prognostic factors. The median neutrophil/lymphocyte ratio (NLR) was adopted as a cutoff value to discriminate patients with low versus high NLR. Early tumor marker decrease was defined as an abnormal parameter with a decrease of &gt; 10% by day 28. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR1900020503. Results: Patients characteristics were not associated with differences in PFS and OS. Seven (14.6%) and 11 (22.9%) patients had initial normal CEA and CA19-9, respectively, and were excluded from the analysis of tumor markers. The median NLR were 4.1. In univariate analysis, low baseline NLR, early CA19-9 decrease, and the hand-foot syndrome (HFS) were associated with good progression-free survival (PFS) [NLR, HR 0.38 (95% CI 0.16–0.89), P = 0.027; CA19-9, HR 0.37 (95% CI 0.16-0.83), P = 0.016; HFS HR 0.23 (95% CI 0.08-0.68, P = 0.007); respectively]. Low baseline NLR and early CA19-9 decrease were also associated with good overall survival (OS) [NLR, HR 0.34 (95% CI 0.17–0.67), P = 0.002; CA19-9, HR 0.46 (95% CI 0.23-0.95), P = 0.035; respectively]. NLR and HFS retained a significant association with PFS [NLR, HR 0.36 (95% CI 0.15–0.84), P = 0.019; HFS, HR 0.25 (95% CI 0.08–0.77), P = 0.016; respectively] while only NLR retained a significant association with OS [NLR, HR 0.35 (95% CI 0.17–0.70), P = 0.019] in the multivariate analysis using the aforementioned factors. Conclusions: Clinical parameters including low baseline NLR, early CA19-9 decrease and HFS could be positive predictive factors of the efficacy of apatinib in mCRC. NLR could be the independent prognostic factor of OS in mCRC. Additional studies are warranted for further validation.
Fluconazole Compared with Ketoconazole for the Treatment of Candida Esophagitis in AIDS
Authors: Loren Laine, Robin H. Dretler, Chris N. Conteas, Carmelita Tuazon, Frederick M. Koster, Fred Sattler, Kathleen Squires, Muhammed Z. Islam
Journal: Annals of Internal Medicine (2020)

Abstract ▪Objective:To determine the clinical and endoscopic response of Candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. ▪Desi...
Analysis of Overall Survival Benefit of Abemaciclib Plus Fulvestrant in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer
Authors: Ryan Sun, Dae Hyun Kim, Lee-Jen Wei
Journal: JAMA Oncology (2020)

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Novel artificial intelligence (AI)-based technology to improve oncology clinical trial fulfillment.
Authors: TJ Bowen, Laura Stephens, Mark Vance, Yancui Huang, Deborah Fridman, Chadi Nabhan
Journal: Journal of Clinical Oncology (2020)

2052 Background: Less than 5% of US adult cancer pts are enrolled on clinical trials. Challenges in clinical trial fulfillment limit available treatment options, slow enrollment and ultimately delay new therapies from reaching market. Pt screening requires multiple clinical team members to find pts that meet strict inclusion/exclusion criteria. We evaluated the impact of new technology, Deep Lens VIPER, in identifying more qualified pts for clinical studies, and reduction of staff burden. Methods: We implemented Deep Lens VIPER at Hoag Hospital (Newport Beach, California), accessing the electronic medical records and pathology systems (EMR/LIS) to effectively identify pts who are candidates for 20 ongoing recruiting clinical studies. VIPER was fed pt data from 5,706 surgical pathology pts over a 4-month period (October 1, 2019 - January 31, 2020). Proprietary AI identification and matching technology was configured to align cancer pts with those 20 clinical studies, each with unique study criteria. Following an initial machine-assisted triage step, a research coordinator was alerted when pts who met protocol criteria were ready for final approval steps. Results were analyzed and a qualitative assessment of usability was also performed. Results: VIPER was able to triage all 5,706 surgical pathology cases (100%), identifying 1,045 pts (18.3%) with malignant neoplasms that would qualify for further analysis for clinical trials enrollment. Further triage based on inclusion and exclusion criteria led to the identification of 150 previously unidentified pts for 16 of the 20 studies. The 16 different studies for which potential pts were identified, included 11 tumor types, 12 biomarkers and 3 basket studies. Working with the VIPER system, 1 novice care team member performed initial identification of all 150 previously unidentified pts. The VIPER system increased monthly candidate pt catchment for 16 of the 20 studies under investigation, which is approximately 600 patients annually added for final triage for studies being conducted. Conclusions: We demonstrate the use of an AI-based platform to identify pts for clinical trial enrollment who would be missed using traditional recruiting methods. One staff member effectively triaged participants from 20 different studies with unique inclusion/exclusion criteria. These studies were previously managed by 6 different care team members with limited time for recruitment. Scaling this platform to additional institutions and more studies is ongoing to validate these findings.