tbuckley/cabot-search huggingface dataset:
The landscape of chromosome 11q13 amplification in Chinese solid tumor patients and hyperprogressive disease (HPD) clinical example.
Authors: Jieli Yu, Minghui Wang, RongFeng Song, Shuben Li, Hongbiao Wang, Jianjiang Xie, Chengzhi Zhou, Kunsong Li, Liangjie Chi, Jian Huang, Zhuojian Shen, Weiguang Gu, Yun Li, Zhen-hai LU, FangQin Xue, Dan Liu, Xiaoliang Shi, Angen Liu, Lin Zhang
Journal: Journal of Clinical Oncology (2020)

e15222 Background: Multiple biomarkers are thought to be effective guides in selecting immune checkpoint inhibitors, such as Tumor mutational burden (TMB), PD-L1 and MSI/dMMR. Immunotherapy may be miraculous effective in some patients but many other patients experienced poor prognosis and even tumor overgrowth after immunotherapy in real practice. Previous studies have reported that 11q13 (CCND1, FGF3, FGF4, and FGF19) amplifications were associated with HPD. However, the characterization of chromosome 11q13 amplification in Chinese solid tumor patients are not clear. Methods: A total of 10167 Chinese solid tumor patients’ FFPE and matching blood samples sequenced by next-generation sequencing (NGS) targeting 450 cancer genes were included in this study. Genomic alterations including single nucleotide variants (SNV), insertions and deletions, copy number variations and fusions were assessed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: Chromosome 11q13 amplifications were identified in 679 (6.7%) Chinese solid tumor patients. The top six tumor types with 11q13 amplification were esophageal carcinoma 43.8%, melanoma 17%, urothelial carcinoma 16%, breast carcinoma 13.4%, head and neck carcinoma 13.1% and hepatocellular carcinoma 9.4%. In 2257 patients with TMB-H (10muts/Mb) / PD-L1 expression / MSI samples, chromosome 11q13 copy number gain were identified in 184 (8.2%) patients. Chromosome 11q13 amplification and MSI were independent events and didn't occur simultaneously. In TMB-H patients, the detection rate of 11q13 amplification was 8.5%, while in PD-L1 positive patients, the amplification rate of 11q13 was 7.4%. In patients with TMB-H and PD-L1 positive, the detection rate of 11q13 amplification was 9.4%. In our clinical practice, we saw example of HPD exist in a lung squamous cell carcinoma patient who was treated with multiple lines of therapy and then used the Nivolumab. The patient underwent genetic testing and was found to be chromosome 11q13 amplified. Conclusions: The proportion of 11q13 amplification was different in different types of solid tumor. Esophageal carcinoma, melanoma and urothelial carcinoma were top three types of solid tumors with 11q13 amplification. The 11q13 amplification did not coincide with MSI but it overlapped with PD-L1 expression or TMB-H. Together, these results may provide immunotherapy guidance in clinical practice.
Physician whistle-blower’s experiences in hematology-oncology safety litigation against pharmaceutical companies.
Authors: Ashley Caitlin Godwin, Shamia Hoque, Jayanth Vemula, Henry C Ausdenmoore, Michael Zhu, Charles L. Bennett
Journal: Journal of Clinical Oncology (2020)

2074 Background: Some clinicians have reported initial series of severe or fatal adverse drug reactions (ADRs) that affected large hematology-oncology patient numbers and for which pharmaceutical manufacturers subsequently paid large settlements or fines for allegedly failing to inform physicians about such ADRs. Based on their large human costs ( &gt; 1,000 serious illnesses or deaths) and large financial costs ( &gt; $100 million in settlements or fines), we have termed these ADRs as titanic ADRs. At a Senate hearing on one titanic, Vioxx, (a COX-2 inhibitor that was evaluated for colorectal cancer prevention), the clinician reporter was termed a “whistleblower” by a senator although this individual had not filed a formal whistleblower lawsuit. We identified physicians who would fit this characterization of whistleblowers and had published titanic hematology-oncology ADR reports in high impact journals. Methods: Hematology-oncology titanic ADRs were identified by collaborators with two NIH-funded drug safety networks (RADAR and SONAR (1998-2019)). Exclusion criteria included having also filed a whistleblower lawsuit. Qualitative research analyses evaluated content of statements made by whistleblowers to national reporters or at congressional hearings. Results: 18 physicians who reported titanic hematology/oncology-associated ADRs in peer-reviewed literature and discussed their findings in national news media outlets are included. Titanic ADRs included death, nephrogenic systemic fibrosis, coronary artery disease, and venous thromboembolism related to COX-2 inhibitors, heparin, gadolinium dye, thalidomide, lenalidomide, epoetin, and darbepoetin. Related financial settlements ranged from $100 million to $4.85 billion. Whistleblowers were from the United States, Denmark, and Germany. Primary motivations were public health and medical awareness. Whistleblowers reported having gone through lawsuits and having had executives request that the whistleblowers’ university terminate employment. One whistleblower was quoted saying “I believe that the lawsuit is an attempt to silence me.” Conclusions: Clinician whistleblowers of titanic hematology-oncology ADRs experienced reputational, financial, and personal threats. Motivations for reporting titanic ADRs were mainly public health and medical awareness focused. This differs from our previous study on clinicians publishing on non-titanic ADRs, where the primary motivation was scientific curiosity.
A phase I clinical trial to assess the safety, pharmacokinetics, and antitumor activity of glumetinib (SCC244) in patients with advanced non-small cell lung cancers (NSCLCs).
Authors: Hua-Jun Chen, Jin-Ji Yang, Xuening Yang, Qing Zhou, Minghui Sun, Yue Li, Ziyong Xiang, Yilong Wu
Journal: Journal of Clinical Oncology (2020)

e21702 Background: Aberrant activation of the MET pathway is associated poor prognosis and poor response to standard therapies in cancer patients. Glumetinib (SCC224) is an oral potent and highly selective MET inhibitor. This is an open label, dose-escalation, phase I clinical study to determine the safety, pharmacokinetics and anti-tumor activity in patients with advanced NSCLC regardless of MET status. Methods: Patients with advanced NSCLC failed standard treatments received glumetinib orally according to one of four dose escalation regimens on a 28-day cycle: 100 mg, 200 mg, 300mg and 400 mg once daily, in a Pharmacologically Guided Dose Escalation (PGDE) design (a variation of the standard 3+3 design). The primary endpoints are the incidence of dose limit toxicity (DLT), maximally tolerated dose (MTD), biologically effective dose (BED). The secondary endpoints are treatment-emergent adverse events (TEAE), safety and tolerability, anti-tumor efficacy, pharmacokinetics, and its metabolites. Results: As of Feb 7, 2020, a total of eighteen eligible (18) patients were enrolled into this study: 3 at 100 mg, 3 at 200 mg, 6 at 300 mg and 6 at 400 mg. Only one patient among 6 evaluable patients at 400mg cohort reported one DLT of grade 3 vomiting. Treatment-related adverse events mostly were grade 1 or 2 nausea, vomiting, elevated alkaline phosphatase, elevated conjugated bilirubin, edema, headache, asthenia and decreased appetite. Non-DLT treatment related G3/4 adverse events were peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%). Absorption was rapid after dosing and the median time to reach maximum plasma drug concentration ( T max ) was 2.0‐6.0 hours. The mean value of half-life(t 1/2 ) in each dose group ranged from 20.43h to 35.36 h. In response to glumetinib, one patient with MET overexpression at 200mg dose level had a best of response of partial response and completed 44 weeks glumetinib treatment, 4 patients (3 with MET amplification) had a best of response of stable disease. Conclusions: Glumetinib was well tolerated at doses up to 400 mg once daily and demonstrated clinical activity in advanced NSCLC with MET alterations. Glumetinib is used in ongoing clinical trials to further explore safety and efficacy in NSCLC. Clinical trial information: NCT03466268.
C反应蛋白升高与心房颤动关系的探讨
Authors: 王云书
Journal: BMJ (2006)

应用免疫比浊法测定92例心房颤动(房颤)患者血清的C反应蛋白(CRP)水平,并与对照组比较.同时,根据房颤的持续时间、病因的不同将患者分为不同亚组进行分析.结果示心房纤颤患者的CRP水平明显高于对照组[(3.9±1.7)mg/L比(0.8±0.5)mg/L,P＜0.05].持续性及永久性房颤组的CRP水平[分别为(3.8±1.2)mg/L、(3.9±1.0)mg/L]均高于阵发性房颤组[(2.4±0.2)mg/L,]P＜0.05.提示血清CRP的升高与房颤的发生有关,并与其持续时间有关。
Using oral morphine-equivalent values to track the analgesic effect of treatments in clinical trials.
Authors: Stephen A Raymond, John F Hutchin, Arnold Degboe, Kenneth G Faulkner
Journal: Journal of Clinical Oncology (2020)

e14075 Background: Patient reported pain is subjective, requiring individuals to grade the feeling of pain as “high” or “low”, typically using a numeric scale. As a supplement to self-reported pain, monitoring the dosage and type of treatment needed to keep pain at a tolerable or comfortable level has been suggested. However, differences in treatments can complicate the ability to compare analgesic effects. One approach to this problem uses a 30 mg oral dose of morphine as a standard to quantify the relative analgesic strength of different pain medications. Methods: For use in clinical research, we developed an application on a handheld device for logging opioid consumption and supporting automated determination of oral morphine equivalents (OME) for commonly prescribed analgesics. We reviewed the literature to prepare a comprehensive database of OMEs for more than 450 commonly prescribed pain medications. From treatment logs (time, dose, and route of administration), the application determines a daily “OME Score” in standardized units of mg of oral morphine. Results: As prescriptions change, the daily OME Score gives a comparable measure to track the utilization of diverse analgesic medications. OME Scores can be categorized using the Analgesic Quantification Algorithm (AQA scale) developed by Chung (1). The AQA scale has eight categories and provides 5 gradations for patients in advanced pain who receive strong opioids, each gradation reflecting adoubling in the daily OME Score. The impact of a therapy on pain may be considered clinically significant depending on the changes in self-reported pain and AQA scores related to the treatment. Conclusions: We have developed a method and associated application for easily logging the time, dose, and route of administration of analgesic treatments. This information can be used to compute the daily OME Score for a wide variety of analgesics. The daily OME score can then be tracked and used to report the AQA score alongside self-reported pain for evaluating pain relief in clinical studies. Reference: 1) Chung KC, Barlev A, Braun AH, Qian Y, Zagari M. Pain Medicine 2014; 15:225-232.
早期识别危重症:急性呼吸衰竭
Authors: 吴东, 陈嘉林
Journal: BMJ (2011)

所谓呼吸衰竭(呼衰),是指由于各种原因引起肺通气和(或)换气功能下降,从而导致机体缺氧(伴或不伴有二氧化碳潴留)的一种临床综合征.在社区工作的全科医师不仅要处理慢性呼衰[例如慢性阻塞性肺疾病(COPD)],也要诊治急性呼衰(例如社区获得性肺炎)。
Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma
Authors: Laura-Sophie Landwehr, Barbara Altieri, Jochen Schreiner, Iuliu Sbiera, Isabel Weigand, Matthias Kroiss, Martin Fassnacht, Silviu Sbiera
Journal: Journal for ImmunoTherapy of Cancer (2020)

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy.We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3+), T helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+) and regulatory T cells (Tregs; CD3+CD4+FoxP3+) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess).86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4+- and CD8+ subpopulations as well. In localized, non-metastatic ACC, the favorable impact of TILs on overall and recurrence-free survival was manifested even independently of ENSAT (European Network for the Study of Adrenal Tumors) stage, resection status and Ki67 index. T helper cells were negatively correlated with glucocorticoid excess (Phi=-0.290, p=0.009). Patients with glucocorticoid excess and low TILs had a particularly poor overall survival (27 vs. 121 months in patients with TILs without glucocorticoid excess).Glucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.
Survey on health knowledge among Yayuncun community residents in Beijing
Authors: Ming-ming Cui, Li-hong Wang, Rui-li Li, Bo-wen Chen
Journal: BMJ (2010)

A baseline survey on health knowledge was conducted in Yayuncun (Asian Games Village) Community in 2004 and 2005 respectively. A sample consisting of 1765 residents aged 15 and above from 600 households, who had lived in the community at least 5 years, was randomly taken; the Beijing Typical Community Resident Questionnaire was used for survey and the participants were followedup annually from 2006 to 2008. The results showed that the awareness rate of food nutrition and disease prevention increased year by year; however, the participants with educational level lower than junior middle school had the lowest rate of overall health knowledge. The main channels for local residents to acquire health knowledge were activities, lectures and other programs with the title of the Olympic Games; the educational level and the year of survey were independent affecting factors on overall health knowledge among residents.

Key words: 
Health knowledge,attitudes, practice;  Questionnaires
EV-202: A phase II study of enfortumab vedotin in patients with select previously treated locally advanced or metastatic solid tumors.
Authors: Justine Yang Bruce, Lajos Pusztai, Fadi S. Braiteh, Seema Rao Gorla, Chunzhang Wu, Joaquina Baranda
Journal: Journal of Clinical Oncology (2020)

TPS3647 Background: Nectin-4, a transmembrane cell adhesion protein, is highly expressed in urothelial carcinoma (UC), breast cancer (BC), non-small cell lung cancer (NSCLC), and gastroesophageal cancers (GEC); targeting Nectin-4 on these tumors may provide a novel treatment approach. Enfortumab vedotin (EV), an investigational human monoclonal antibody-drug conjugate, binds to Nectin-4 and upon internalization releases MMAE resulting in cell cycle arrest and cell death. Recently, EV received accelerated approval by the FDA for the treatment of adults with locally advanced/metastatic UC who previously received a PD-1 or PD-L1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Use of EV in this study is investigational. Methods: This open-label phase 2 study (NCT04225117) will assess the efficacy and safety/tolerability of EV in patients (pts) with previously treated locally advanced/metastatic malignant solid tumors. Adult pts (~240) with histologically or cytologically confirmed disease and an ECOG ≤1 will be enrolled into 1 of 6 tumor-specific cohorts (Table), with ~40 pts each. While Nectin-4 expression is not required for enrollment, it is being tested retrospectively. Patients with active CNS metastases, grade ≥2 preexisting sensory or motor neuropathy, grade ≥3 immunotherapy-related hypothyroidism or panhypopituitarism, ongoing grade &gt;3 immunotherapy-related AEs requiring high-dose steroids, or a history of uncontrolled diabetes mellitus within 3 months of the study will be excluded. All pts will receive EV 1.25 mg/kg IV on Days 1, 8, and 15 of each 28-day cycle until treatment discontinuation criteria are met; dose reductions/interruptions will be permitted. For all cohorts, the primary endpoint is investigator-assessed confirmed objective response rate (RECIST v1.1); secondary endpoints include duration of response, disease control rate, progression-free and overall survival, and safety/tolerability of EV. This study is recruiting as of February 2020. Clinical trial information: NCT04225117 . [Table: see text]
不明原因慢性咳嗽与胃食管反流的关系分析
Authors: 朱礼星
Journal: BMJ (2005)

对41例胸部X片、组织胺激发试验、鼻部检查正常的慢性咳嗽患者进行24 h食管pH值监测,并利用症状相关性概率(symptom association probability,SAP)分析咳嗽与反流的相关性.对Demeester总积分≥14.72和(或)SAP≥75%者进行为期12周的抗反流治疗.对规范完成疗程后咳嗽未控制或者未完全控制的患者,在继续原抗反流治疗的同时,加用普米克都保(布地奈德)200 μg/次和奥克斯都保(福莫特罗)9 μg/次,2次/d 吸入,疗程8周.结果显示41例中26例诊断为胃食管反流并给予抗反流治疗,完成疗程后,其中12例咳嗽完全消失;另14例加用吸入性制剂治疗后,9例治愈,3例有效,2例无效.提示胃食管反流除可以作为独立原因引起慢性咳嗽外,还可以与过敏性因素叠加引起咳嗽.抗反流治疗对胃食管反流相关的慢性咳嗽有较好的近期疗效。
Epidemiologic and clinical features of pattern III frontal fibrosing alopecia (pseudo fringe type): A multicenter series of 38 patients
Authors: Daniel Fernandes Melo, Taynara de Mattos Barreto, David Saceda-Corralo, Carla Jorge Machado, Flavia Xavier de Brito, Mariana Tebet, Violeta Duarte Tortelly, Oscar M. Moreno-Arrones, Sérgio Vañó-Galván
Journal: Journal of the American Academy of Dermatology (2020)
The systemic inflammation response index (SIRI) predicts oncological outcome and correlates with tumor burden in metastatic pancreatic cancer.
Authors: Vilma Pacheco Barcia, Talya France, Jamil Asselah, Rebeca Mondejar, Nuria Romero-Laorden, George Zogopoulos, Rosario Serrano, Olga Donnay, Jacobo Rogado Revuelta, Lourdes Del Campo, Elia Martinez, Elena Martin-Perez, Carmen Arlanzón, Katie Guo, Pilar Ochoa, Thierry Alcindor, Gabriel Barrena Castello, Ramon Colomer
Journal: Journal of Clinical Oncology (2020)

e15537 Background: The SIRI, defined by neutrophil x monocyte/lymphocyte 10 9 /L, has recently emerged as a prognostic factor for pancreatic cancer. However, the association between SIRI values after chemotherapy and tumor response has not been evaluated. Methods: 161 metastatic pancreatic cancer patients were retrospectively analyzed. Associations between overall survival (OS), chemotherapy and SIRI were analyzed. A larger number of patients with pre-treatment SIRI (pre-SIRI) were collected so, post-treatment SIRI (post-SIRI) evaluated after three cycles of chemotherapy, was adjusted for analysis. Results: Median age 66 years. 59 (36%) received gemcitabine + nab-paclitaxel, 40 (24%) gemcitabine, 22 (17%) mFOLFIRINOX, 13 (7%) other regimens. 27 (16%) had not received treatment. Pre-SIRI≥2.3×10 9 /L was an independent, negative predictor of OS compared to pre-SIRI &lt; 2.3×10 9 /L [5 versus 16 months, Hazard Ratio (HR) 2.87, Confidence Interval (CI) 95% 2.02-4.07, P&lt; 0.0001]. In the whole cohort, we observed SIRI values increased after treatment (median pre-SIRI: 1.6×10 9 /L; post-SIRI: 2.3×10 9 /L; P= 0.007). Thus, we analyzed the association between tumor response measured by RECIST and pre-SIRI and post- SIRI values. Patients with progressive disease (PD) showed a higher pre-SIRI than those who had a response to chemotherapy (2.7×10 9 /L versus 1.2×10 9 /L, respectively; P&lt; 0.001). We also observed a statistically significant increase in post-SIRI values for PD compared to tumor response (3.2×10 9 /L versus 1.7×10 9 /L, respectively; P= 0.012). As observed for pre-SIRI, post-SIRI ≥2.3×10 9 /L showed a shorter OS compared to post-SIRI &lt; 2.3×10 9 /L (8 versus 17 months, respectively; P= 0.016). Furthermore, patients with pre-SIRI ≥2.3×10 9 /L were more likely to benefit from mFOLFIRINOX showing a median OS of 17 months compared to 6 and 4 months for gemcitabine + nab-paclitaxel and gemcitabine, respectively ( P&lt; 0.001). Conversely, there was no difference for pre-SIRI &lt; 2.3×10 9 /L: 15.9 months versus 16.5 and 16, respectively. Conclusions: SIRI≥2.3×10 9 /L was a prognostic factor for metastatic pancreatic cancer. An elevated post-SIRI showed an association with disease progression and a negative impact on survival. Therefore, an increase in SIRI could be related to high tumor burden and be useful to appropriately select patients who would benefit of a more intensive first-line chemotherapy regimen.
A cost analysis of managing cancer-related pain among hospitalized US cancer patients.
Authors: Olatunji B. Alese, Chao Zhang, Katerina Mary Zakka, Sungjin Kim, Christina Wu, Walid Shaib, Mehmet Akce, Zhengjia Chen, Jeffrey M. Switchenko, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2020)

7079 Background: Pain is a common symptom of cancer, affecting patients' function and quality of life. It is also a common cause of hospitalization for cancer patients. The aim of this study was to evaluate the cost of in-hospital pain management among US cancer patients. Methods: A retrospective analysis of data from all US hospitals that contributed to the National Inpatient Sample for 2011-2015 was conducted. All cancer patients admitted for pain management were included in the analysis. Main outcomes were factors significantly associated with hospital length of stay, total charge per hospital stay, and in-hospital mortality. Weighted chi-square test was used for categorical covariates and univariate analysis was performed using a logistic model. Results: 122,776 patient discharges were identified. Mean age was 59.3 years and 52.3% were female. 65.9% stayed in the hospital for longer than 72 hours, with a median total hospital charge of $48,156. Conversely, the median total hospital charge for those spending less than 72 hours on admission was $15,966. Median total charge per hospital stay was similar among insured and uninsured/self-pay patients ($32,879 vs. $32,323; p=0.013), but higher in patients without metastatic disease ($33,315 vs. $29,369; p&lt;0.001). It was also higher in those with the highest income quartile when compared with lowest income patients ($38,223 vs. $30,047; p&lt;0.001). Co-morbid medical illnesses were more prevalent in those with longer hospital stay (15 vs. 12; p&lt;0.001) and the overall in-hospital mortality rate was 8.2%. There was no significant difference in median total hospital charges between those who died in, or those discharged from the hospital ($33,746 vs. $32,795; p&lt;0.001). On multivariate analyses, gender, race, insurance status, diagnosis of metastatic cancer, age, number of co-morbid medical illnesses, year of diagnosis, and median income were significant predictors of length of stay. Race, insurance payor, metastatic cancer, age, and number of co-morbid medical illnesses were significant predictors of total hospital charges, after adjusting for other covariates. Conclusions: In-patient pain management of cancer patients is associated with significant health care costs. Optimization of outpatient pain management strategies could significantly lower the cost of care for cancer.
Descending necrotizing mediastinitis: report of two cases and literature review
Authors: Ting Chen, Min-hua Shi
Journal: BMJ (2009)

We reported 2 cases of descending neerotizing mediastinitis (DNM) and reviewed the related literatures. The etiology, clinical manifestations, imaging manifestations, diagnostic criteria and therapeutic strategies of DNM were discussed. It is concluded that descending necrotizing mediastinitis is a life-threatening disease with high mortality and is prone to be misdiagnosed. Early diagnosis, prompt application of sensitive broad-spectrum antibiotics and abscess drainage with proper surgical medality may improve the prognosis of DNM. 

Key words: 
Mediastinitis;  Infection