tbuckley/cabot-search huggingface dataset:
Clinical characteristics and treatment outcomes of 65 patients with BRAF-mutated non-small cell lung cancer (NSCLC).
Authors: Yuxin Mu, Ke Yang, Xuezhi Hao, Yan Wang, Lin Wang, Yutao Liu, Lin Lin, Li Junling, Puyuan Xing
Journal: Journal of Clinical Oncology (2020)

e21745 Background: BRAF mutations are infrequently seen in non-small cell lung cancer (NSCLC) in Chinese population. We aimed to investigate the clinicopathologic characteristics and treatment outcomes of Chinese patients with NSCLC harboring BRAF mutations. Methods: We conducted a retrospective multicenter study in China of patients with NSCLC harboring BRAF mutations between Jan 2017 and Jul 2019. Results: A total of 65 patients treated in 22 centers were included, 54 harbored BRAF-V600E mutation and 11 had non-V600E mutations, including K601E, G469S, G469V, G469A, G596R, G466R and T599dup. No significant difference in age or gender was found between BRAF-V600E and non-V600E cases, while the majority of patients with non-V600E mutations were smokers (81.8%). Of the 18 patients with early-stage disease at diagnosis and underwent a resection, the median disease-free survival (DFS) was 43.2 months, 18.7 months and 10.1 months of stage I, II and IIIA patients (P = 0.07), respectively. In 46 patients with advanced-stage disease at data cutoff, disease control rate (DCR) and progression-free survival (PFS) of first-line anti-BRAF targeted therapy was superior than chemotherapy in patients harboring BRAF-V600E mutation (DCR, 100.0% vs. 70.0%, P = 0.027; median PFS, 9.8 months vs. 5.4 months, P = 0.149). Of 30 V600E-mutated patients who received anti-BRAF therapy during the course of disease, the median PFS of vemurafenib, dabrafenib, and dabrafenib plus trametinib was 7.8 months, 5.8 months and 6.0 months, respectively (P = 0.970). Median PFS were similar between V600E and non-V600E patients (5.4 months vs. 5.4 months, P = 0.825) to first-line chemotherapy. Nine patients were treated with checkpoint inhibitors, DCR and median PFS were 62.5% and 3.0 months (95%CI 2.9, 3.1), respectively. Conclusions: Our data demonstrated the clinical benefit of anti-BRAF targeted therapy in Chinese NSCLC patients harboring BRAF-V600E mutation. The value of immunotherapy and treatment selection among non-V600E population needs further study.[Table: see text]
西部新生儿论坛及西北新生儿协作网(组)成立大会纪要
Authors: 刘俐, 邱银萍
Journal: BMJ (2012)

由中华医学会《中华全科医师杂志》编辑委员会、西安交通大学医学院第一附属医院、西北地区新生儿协作网(组)、西安医学会新生儿分会联合主办的西部新生儿论坛暨西北地区新生儿协作网(组)成立大会,于2012年4月6至9日在西安召开,来自陕西省卫生厅、西安交通大学及附属医院的有关领导到会祝贺,350余名代表参加了会议,二十余位国内外著名新生儿专家做了精彩的专题报告。
IGM-8444 as a potent agonistic Death Receptor 5 (DR5) IgM antibody: Induction of tumor cytotoxicity, combination with chemotherapy and <i>in vitro</i> safety profile.
Authors: Beatrice Wang, Ling Wang, Tasnim Kothambawala, Susan Calhoun, Thomas Matthew, Genevive Hernandez, Marvin Peterson, Angus Sinclair, Eric William Humke, Bruce Keyt
Journal: Journal of Clinical Oncology (2020)

3595 Background: Death receptor 5 (DR5) is a member of the tumor necrosis factor (TNF) receptor superfamily that multimerizes when bound to its ligand, TNF-related apoptosis inducing ligand (TRAIL), to activate the extrinsic apoptotic pathway. DR5 is broadly expressed on solid and hematologic cancers and has been targeted with both recombinant TRAIL and agonistic antibodies in the clinic. However, these therapeutics have generally been unsuccessful due to toxicity or lack of efficacy. We have developed a multivalent IgM DR5 agonist, IGM-8444, that multimerizes DR5 to selectively and potently induce tumor cell apoptosis while maintaining tolerability. Methods: IGM-8444 is an engineered, pentameric IgM antibody with 10 binding sites specific for DR5. Human tumor cell lines or hepatocytes were evaluated in vitro for dose dependent IGM-8444 induced cytotoxicity. The efficacy of IGM-8444 was evaluated with or without chemotherapy, in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse tumor models, with IGM-8444 administered at various dose levels and schedules when tumors reached approximately 100 mm 3 . Sera and tumors were analyzed for biomarkers of tumor apoptosis. Results: In vitro cytotoxicity assays identified IGM-8444 activity across cell lines from 18 solid and hematologic malignancies. In IGM-8444 partially resistant cell lines, combination with chemotherapy or a Bcl2 inhibitor enhanced in vitro cytotoxicity. IGM-8444 was efficacious as a monotherapy in CDX and PDX tumor models including colorectal, lung, and gastric indications. In a gastric PDX model, IGM-8444 induced complete and durable dose-dependent tumor regressions. In vivo, combination of IGM-8444 with standard-of-care chemotherapies, such as irinotecan, led to enhanced efficacy. IGM-8444 administration increased markers of tumor apoptosis, identifying potential clinical pharmacodynamic biomarkers. At doses several log-fold higher than efficacious doses, IGM-8444 demonstrated a favorable single agent in vitro safety profile, with little to no in vitro cytotoxicity observed using primary human hepatocytes from multiple donors. Conclusions: These data support the clinical development of IGM-8444 in both solid and hematological malignancies as a single agent and in combination with standard of care therapy. IGM-8444 is projected for IND filing in 2020.
宫内节育器异位于宫颈一例
Authors: 王海燕, 徐明彩, 徐志彦, 侯向青
Journal: BMJ (2008)

患者女,34岁,G3P1A2L1.因取宫内避孕器(IUD)后未孕4年于2007年9月24日就诊于我院.结婚14年,13年前足月妊娠自然分娩一女孩,于产后9个月行人工流产1次.10年前放置O形IUD 1枚,放置后1个月因停经行B超检查示早孕,行人工流产术,术中未探及IUD。
Outcome of mammography examination among asymptomatic women.
Authors: Hadijat Oluseyi Kolade-Yunusa
Journal: Journal of Clinical Oncology (2020)

e13558 Background: Early detection of breast cancer is important in reducing mortality, morbidity and high socio-economic burden associated with it. Mammography is currently the primary imaging modality used as a screening tool to detect early breast cancer in women experiencing no symptoms as they are most curable in the early stage. The aim of the study is to determine the mammographic outcome in asymptomatic women who presented for mammographic breast examination in Abuja,Nigeria. Methods: This descriptive cross-sectional study comprises of 113 asymptomatic women who presented for mammographic examination at the Radiology department of University of Abuja Teaching Hospital, Gwagwalada from March 2015 to December 2018. Two basic views (craniocaudal and mediolateral views) of the breast were obtained using EXR-650 machine.Additional views were obtained when necessary. Images of the breast were review by radiologist. Results: The mean age of study population was 40.72 ±10.45years with age range of 35 and 65 years. The mammographic outcome among asymptomatic women who had mammographic examination was negative in 69(61.1%) women and positive in 44(38.9%). The differences observed between the positive and negative mammographic outcome was statistically significant p = 0.01. The positive outcome noted in mammograms of women examined were: benign mass in 18(15.9%) women; 9(8.0%) had benign calcification; 7(6.2%) showed architectural distortion; 5(4.4%) was inconclusive; focal asymmetry in 3(2.6%); and suspicious mass in 2(1.8%). Conclusions: Mammogram is an important tool for screening and diagnoses of breast pathologies. In this study, screening of women reveals various benign and malignant breast changes which necessitate early interventions. Early detection of breast cancer save lives. [Table: see text]
Effectiveness of new rural cooperative medical management for patients with chronic obstructive pulmonary disease in stage I
Authors: De-qi Zou, Xue-shun Zhang, Yan-li Xu, Hai Gao, Jian-wei Zhao, Ning Lu
Journal: BMJ (2012)

Objective To evaluate the effectiveness of management for patients with chronic obstructive pulmonary disease (COPD) in stage Ⅰ at new rural cooperative medical facilities.Methods A quasi-experiment design was used for the evaluation of patients registering at Dongcun and Fangyuan subdistrict offices in Haiyang.And 79 COPD cases from Dongcun sub-district offices were selected into the management group while 76 cases from Fangyuan the control group.The measures at the new rural cooperative medical facilities included smoking-free publicity,avoiding a hazardous environment,application of influenza vaccines and training of patients and local general practitioners in essences of COPD prevention and treatment.Except for routine treatment,no special measures were taken for the control group.Results Sixty-one patients in the management group and 60 in the control group completed a 3-year follow-up.Fifteen patients were smokers during their initial visits in the management group and 13 quitted smoking after a 3-year management.Meanwhile 19 patients were smokers during their initial visits in the control group and 3 of them quitted smoking within the same period.The decrement of BODE index between post-management at year 2&3 and between pre-management was higher in the management group versus the control group within the same period (P ＜ 0.01).The annual average frequencies of common cold,acute attack and physician consultation were obviously lower post-management at year 3 than those pre-management and the control group within the same period ( P ＜ 0.05 ).Lung functions of two groups deteriorated as compared with those 3 years before ( P ＜ 0.05).But no statistical difference existed between two groups (P ＞ 0.05).Conclusion The management of COPD patients in stage Ⅰ at new rural cooperative medical facilities can improve their quality of life and reduce their frequencies of common cold,acute attack and physician consultation.

Key words: 
Pulmonary disease,chronic obstructive; Disease management; Evaluation studies; New rural cooperative medical
Acute Liver Injury in COVID‐19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort
Authors: Meaghan M. Phipps, Luis H. Barraza, Elijah D. LaSota, Magdalena E. Sobieszczyk, Marcus R. Pereira, Elizabeth X. Zheng, Alyson N. Fox, Jason Zucker, Elizabeth C. Verna
Journal: Hepatology (2020)

Background and Aims Coronavirus disease 2019 (COVID‐19) has been associated with acute liver injury (ALI) manifested by increased liver enzymes in reports worldwide. Prevalence of liver injury and associated clinical characteristics are not well defined. We aim to identify the prevalence of and risk factors for development of COVID‐19‐associated ALI in a large cohort in the United States. Approach and Results In this retrospective cohort study, all patients who underwent SARS‐CoV‐2 testing at three hospitals in the NewYork‐Presbyterian network were assessed. Of 3,381 patients, 2,273 tested positive and had higher initial and peak alanine aminotransferase (ALT) than those who tested negative. ALI was categorized as mild if ALT was greater than the upper limit of normal (ULN) but &lt;2 times ULN, moderate if ALT was between 2 and 5 times the ULN, and severe if ALT was &gt;5 times the ULN. Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury (SLI). In multivariable analysis, severe ALI was significantly associated with elevated inflammatory markers, including ferritin (odds ratio [OR], 2.40; P &lt; 0.001) and interleukin‐6 (OR, 1.45; P = 0.009). Patients with SLI had a more severe clinical course, including higher rates of intensive care unit admission (69%), intubation (65%), renal replacement therapy (RRT; 33%), and mortality (42%). In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR, 1.14; P = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and RRT. Conclusions ALI is common in patients who test positive for SARS‐CoV‐2, but is most often mild. However, among the 6.4% of patients with SLI, a severe disease course should be anticipated.
肺原发恶性血管外皮细胞瘤一例
Authors: 王砚东, 郭勇, 王延红, 王雷, 付强, 董家豪, 齐波
Journal: BMJ (2008)

恶性血管外皮细胞瘤(malignant lhemangiopericytoma.MH)是起源于血管Zimmerman外皮细胞的一种少见血管肿瘤,大约占全部血管肿瘤的1%,原发于肺部者更为罕见.我院1994年收治1例,经手术治疗,已存活14年。
Characterization of hypoxia signature to evaluate the tumor immune microenvironment and predict prognosis in glioma.
Authors: Shihong Wu, Wanzun Lin, Youliang Weng, Yuhui Pan, Zongwei Huang, Miaomiao Li, Ting Lin, Xiaochuan Chen, Lurong Zhang, Sufang Qiu
Journal: Journal of Clinical Oncology (2020)

e14534 Background: Glioma, the most common primary brain tumor, accounts for more than 50% of all primary brain tumors. Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Hypoxia is a driver of the malignant phenotype in glioma; it triggers a cascade of immunosuppressive processes and malignant cellular responses (tumor progression, metastases, and resistance to chemoradiotherapy), which result in disease progression and poor prognosis. However, approaches to determine the extent of hypoxia in the tumor microenvironment are still unclear. Methods: Here, we enrolled 1626 glioma patients with RNA sequence and survival data in two independent cohorts, and developed a hypoxia risk model to reflect the immune microenvironment in glioma and predict prognosis. Results: High hypoxia risk score was associated with poor prognosis and indicated an immunosuppressive microenvironment. Hypoxia signature significantly correlated with clinical and molecular features and could serve as an independent prognostic factor for glioma patients. Moreover, Gene Set Enrichment Analysis showed that gene sets associated with the high-risk group were involved in carcinogenesis and immunosuppression signaling. Conclusions: In conclusion, we developed and validated a novel hypoxia risk model, which served as an independent prognostic indicator and reflected overall immune response intensity in the glioma microenvironment.
Recurrent or metastatic salivary gland tumor (MSGT) patients treated with selinexor, a first in class selective exportin-1 (XPO1) inhibitor.
Authors: Eoghan Ruadh Malone, Anna Spreafico, Ilan Weinreb, Sarah Jennings, Lindsay Carlsson, Ahmad Noori, Lisa Wang, Lillian L. Siu, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2020)

6586 Background: MSGT are rare with limited systemic treatments. This single institution, prospective study in recurrent or metastatic (RM) MSGT involved 2 phases: genomic profiling followed by treatment with either genomically-matched or unmatched therapy. Here we present the results of the unmatched arm for patients (pts) treated with S an oral selective inhibitor of XPO1 that leads to activation of tumor suppressor proteins and retention of oncoprotein mRNAs in the cell nucleus, inducing cancer cell apoptosis. Methods: Patients (pts) with RM-MSGT had archived paraffin embedded tumor samples profiled with targeted next generation sequencing, immunohistochemistry for androgen receptor (AR) and fluorescent in-situ hybridization for HER-2 and ALK. If no actionable mutations were identified or if no matched agents were available, pts with progressive disease could receive S (60mg given twice weekly Q28 days). The study had a simon-2 stage design; 1 partial response in the first 18 pts treated with S, would trigger an additional 7pts to receive S in stage 2. Results: Between July 2014 and April 2019 85 pts were enrolled on study: 73 had sequencing which identified 41 with no actionable mutations and 32 with actionable mutations. 18 pts (10F/8M, median age 61 years [40-79]) were treated with S and included adenoid cystic (n = 8), salivary duct (n = 4), acinic cell (n = 2) and other subtypes (n = 4). Of these 18, 4 pts had actionable aberrations: AR amplification (n = 2), mutations in SMARCB1 (n = 1) and CDKN2A (n = 1). 13pts were treatment naïve, 3pts and 2pts received 1 and 2 or more lines of treatment respectively prior to enrollment: androgen deprivation therapy (n = 2), chemotherapy (n = 3), early phase clinical trials (n = 3). The median number of cycles of S received were 3 (range: 1-19). The best response by RECIST was SD in 13pts (72%) (SD &gt; 6 months (range: 6-18 months) in 5pts (28%); tumor reduction measured in 7pts (39%)), no PRs, PD in 3pts (17%), and 2pts (11%) were not evaluable for response due to insufficient duration of treatment coming off early due to toxicity. The median PFS (95% CI) was 7.6 (3.5-NA) months and the median OS (95% CI) was 15.4 (7.3-NA) months. The most common drug-related toxicities were grade 1-2 fatigue 14pts (78%), nausea 13pts (72%) and dysguesia 10pts (56%). 5 (28%) pts had a dose reduction and 6 (33%) in total had a dose interruption due to toxicity. Conclusions: Single agent antitumor activity was limited and the side effect profile was tolerable. No specific genomic aberration was associated with response to S. Clinical trial information: NCT02069730 .
Comparison of different systemic therapeutic regimes in resectable high-risk soft tissue sarcoma: Results of a network meta-analysis.
Authors: Jan Haussmann, Wilfried Budach, Edwin Boelke, Balint Tamaskovics, Freddy Joel Djiepmo Njanang, Stefanie Corradini, Kai Kammers, Ruediger Wessalowski, Christiane Matuschek
Journal: Journal of Clinical Oncology (2020)

11549 Background: The treatment of high-risk soft tissue sarcoma of the trunk or the extremities consists of surgical resection with risk-adapted radiation therapy. Further treatment options which can significantly improve local and systemic tumor control including chemotherapy are not well established. Due to the heterogeneity of disease different systemic approaches as well as their application during different time points have been attempted. Methods: We conducted a literature search for randomized clinical trials in the treatment of localized, resectable high-risk soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints of overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model (ivhet) with the help of the Microsoft Excel add-in Meta-XL V5.3. Results: The literature search identified 25 studies including 3489 patients. The network analysis showed that adjuvant chemotherapy (adjCTx) results in a significant improvement in overall survival (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017) compared to the standard treatment of surgery ± radiatherapy alone. Combined treatment with regional hyperthermia and neoadjuvant chemotherapy (HTx+nadjCTx) also improves OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Preoperative chemotherapy alone (nadjCTx) as well as perioperative chemotherapy (periopCTx) resulted both in non-statistically significant improvements in OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195) and (HR = 0.48; CI-95%: 0.15-1.55; p = 0.218). Histology-tailored neoadjuvant chemotherapy (tNaCTx) also showed no effect on overall survival (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The analysis of DFS, LRFI and DRFI disclosed a similar pattern between the different treatment regimens. Conclusions: The addition of cytotoxic chemotherapy in resectable high-risk soft tissue sarcomas provides a measurable benefit in overall survival. Shifting of systemic therapy to the neoadjuvant setting and combination with regional hyperthermia might be favored. Predictive clinical and molecular markers are needed to evaluate and limit potentional risks prospectively going forward.
上颌窦双腔畸形并鼻窦牙一例
Authors: 卞新浩
Journal: BMJ (2009)

患者女,34岁,因CT发现右侧上颌窦内骨样肿块1个月于2008年1月20日入住我院.该患者入院前因右侧间歇性鼻塞伴头昏、头痛在外院行头部CT扫描,发现右侧上颌窦内密度增高且大部分为高密度骨样阴影,窦底有一颗牙样高密度影。
The application of dynamic monitoring of circulating tumor DNA for detecting minimal residual disease and predicting recurrence in colorectal cancer patients.
Authors: Hiu Ting Chan, Satoshi Nagayama, Yoon Ming Chin, Masumi Otaki, Rie Hayashi, Kazuma Kiyotani, Yosuke Fukunaga, Masashi Ueno, Yusuke Nakamura, Siew-Kee Kee Low
Journal: Journal of Clinical Oncology (2020)

e15531 Background: Although the prognosis of colorectal cancer (CRC) has improved in the past decade, a subset of CRC patients may still suffer from relapse due to the progression from minimal residual disease (MRD) after surgical resection. A sensitive and non-invasive method to detect MRD and early diagnosis of recurrence disease is warranted to start therapeutic interventions at an earlier timing and improving the overall survival rate. In this study, we have evaluated the feasibility of circulating tumor DNA (ctDNA) analysis to detect MRD and early detection of recurrence in CRC patients. Methods: Plasma samples were collected prospectively from 38 CRC patients (stage I to IV), who underwent surgical resection. Preoperative blood samples were obtained just before surgery and post-operative samples were collected at multiple time-points to monitor the changes of tumor mutation profiles. Tumor-derived mutations were detected in preoperative blood samples as well as surgically resected-tumor tissues using ultradeep targeted next generation sequencing. Patient-paired peripheral blood cells (PBCs) were sequenced concurrently to exclude clonal hematopoiesis-related mutations. Results: Among the 38 patients, 74 non-synonymous mutations were identified in tumor tissues and 64 mutations in the preoperative plasma samples. Paired PBCs sequencing identified 11 mutations in plasma samples to be clonal hematopoiesis-related mutations. After the exclusion of clonal hematopoiesis-related mutations, 34 (89.5%) of the 38 patients harbors at least one somatic mutation either from tumor tissues or plasma samples to be monitored longitudinally. ctDNA was detectable in 5 of 14 (36%) post-surgical samples of patients who did not receive adjuvant chemotherapy and in 9 of 18 (50%) post-chemotherapy samples. Up to date, 6 patients have been detected with clinical recurrence and ctDNA analysis identified all 6 recurrences before imaging. Serial ctDNA analyses were able to detect disease recurrence up to 6 months before imaging tests. Furthermore, all patients that were ctDNA negative post-operative or post-chemotherapy showed no signs of clinical relapse. Conclusions: Our current results indicate that ctDNA analysis allows the detection of MRD in CRC patients. The integration of ctDNA analysis with current standard monitoring guidelines holds great promise in early detection of recurrence to allow clinical intervention to be applied promptly.