tbuckley/cabot-search huggingface dataset:
<i>TP53</i> fusions with next-generation sequencing (NGS) in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
Authors: Huafei Chen, Wen xian Wang, Chunwei Xu, You-cai Zhu, Wu Zhuang, Yun-jian Huang, Yong Fang, Hong Wang, Yinbin Zhang, Yafei Wang, Meifang Chen, Jinluan Li, Liping Wang, Shangli Cai, Meiyu Fang, Gang Chen, Tangfeng Lv, Yong Song
Journal: Journal of Clinical Oncology (2020)

e21742 Background: Currently, with the advances in detection techniques, such as next generation sequencing (NGS), more and more rare or atypical TP53 fusions had been identified. Such as TP53-PSMD14, the importance of EGFR signaling in the pathogenesis of lung cancer and the efficacy of EGFR-TKI treatment had been demonstrated. The aim of this study was to evaluate the prevalence of TP53 fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. A total of 2743 patients with NSCLC were screened by using next-generation sequencing (NGS)-based 381 genes panel assay for detecting TP53 fusions. Results: Of this entire cohort, just four (0.15%) patients were identified with a TP53 fusion, including DNAH2-TP53 (1), TP53-MPDU1 (1), TP53-FXR2 (1), TP53-VEZF1 (1). Of the TP53 fusion NSCLC patients, 50.00% were detected in female patients. Biopsies were obtained from primary lung tumor (25.00%) and metastatic sites (75.00%). Overall TMB in the TP53 fusion was high, which had more than 20 mut/Mb. Of the TP53 fusion NSCLC, two cases (50.00%) featured EGFR SV alterations. Conclusions: The frequency of TP53 fusions in Chinese populations with NSCLC is extremely rare (0.17%). TP53 fusions may reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions or exon 21 L858R.
两种方法预防肝硬化胃食管静脉出血的对照研究
Authors: 柴同海, 刘春安, 李曙晖, 王静, 杜荣莲, 俞景奎, 张春清, 周焕明
Journal: BMJ (2006)

将125例肝硬化门静脉高压患者随机分为食管胃底静脉栓塞+部分性脾动脉栓塞组(60例)和胃底静脉断流+脾切除组(65例),对比两组治疗前后食管胃底曲张静脉的变化、血液学指标、再出血率、死亡率及手术并发症发生率等.结果示治疗后两组食管胃底曲张静脉消失情况、血液学指标、因曲张静脉破裂再出血率差异无统计学意义,而手术并发症发生率、因手术导致的Child-Pugh C级患者死亡率及胃黏膜病变所致出血率,差异有统计学意义(P<0.05)。
Association of serum visceral adipose tissue-derived serine protease inhibitor levels with carotid atherosclerosis in elderly patients with type 2 diabetes
Authors: Wei Xia, Zhi-gang Zhao, Hui-feng Zhang
Journal: BMJ (2011)

The serum levels of visceral adipose tissue-derived serine protease inhibitor (vaspin)were measured in 65 elderly type 2 diabetic patients with carotid atherosclerosis( T2DM + CA group), 63 elderly type 2 diabetic patients without carotid atherosclerosis (T2DM group ) and 55 normal elderly individuals( NC group)by enzyme-linked immunosorbent assay. The results showed that the serum vaspin levels in T2DM + CA group were significantly lower than those in T2DM group[(0. 23 ± 0. 13 ) μg/L vs.(0. 41±0. 16)μg/L, P ＜0. 01]. The serum vaspin levels in T2DM + CA group and T2DM group were significantly lower than those in NC group respectively[(0. 63 ± 0. 11 ) μg/L, P ＜ 0. 01 and P ＜ 0. 05].Logistic regression analysis showed that high sensitivety C-reactive protein and Homeostasis Model Assessment insulin resistance index (HOMA-IR) were negatively correlated with serum vaspin levels,which indicates that lower serum vaspin levels might be associated with the pathogenesis of carotid atherosclerosis in elderly type 2 diabetic patients.

Key words: 
Diabetes mellitus;  Atherosclerosis
A novel xenonucleic acid mediated molecular clamping technology for early colorectal cancer diagnostics.
Authors: Qing Sun, Larry Pastor, Jinwei Du, Michael Joseph Powell, Aiguo Zhang, Walter Bodmer, Michael Y. Sha
Journal: Journal of Clinical Oncology (2020)

e16106 Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called ColoScape for early colorectal cancer diagnostics. Methods: Nineteen mutations in four genes APC, KRAS, BRAF and CTNNB1 associated with early events in CRC pathogenesis are targeted in the ColoScape assay. Xenonucleic Acid (XNA) mediated qPCR clamping technology was applied to minimize the wild-type background amplification in order to improve assay sensitivity of CRC mutation detection. The assay analytical performance was verified and validated, cfDNA and FFPE CRC patient samples were assessed for clinical performance, and a ROC curve was applied to evaluate its performance. Results: The data showed that the assay analytical sensitivity is 0.5% Variant Allele Frequency, corresponding to ~7-8 copies of mutant DNA with 5ng total DNA input per test. This assay is highly reproducible with intra-assay CV &lt; 3% and inter-assay CV &lt; 5%. We have investigated 380 clinical samples including plasma cfDNA and FFPE samples from patients with different stages of CRC. The preliminary assay clinical specificity and sensitivity for cfDNA were 100% (95% CI, 80.3-97.5%) and 92.2% (95% CI, 94.7-100%) respectively with AUC being about 0.96; and 96% (95% CI, 77.6-99.7%) specificity and 92% (95% CI, 86.1-95.6%) sensitivity with AUC 0.94 for FFPE. Conclusions: XNA mediated molecular clamping assay is a rapid, precise, and sensitive assay for the detection of CRC mutations in cfDNA or FFPE samples.
Geriatric assessment (GA) predictors of 1y mortality in older adults with gastrointestinal (GI) malignancies: Results from the CARE study.
Authors: Grant Richard Williams, Chen Dai, Mustafa Al Obaidi, Smith Giri, Kelly Kenzik, Andrew Michael McDonald, Crystal Young Smith, Olumide B. Gbolahan, Ravi Kumar Paluri, Joshua Richman, Smita Bhatia
Journal: Journal of Clinical Oncology (2020)

12047 Background: Chronologic age is an imperfect predictor of morbidity and mortality in older patients with newly-diagnosed GI malignancies. Identifying patients with GI malignancies that are at increased risk of mortality within the 1 st year remains challenging given no prior studies have focused on this population, yet is critical to developing personalized treatment plans. To fill this gap, we examined predictors of 1y mortality using variables from a patient-reported GA in a prospective cohort of older adults with GI malignancies. Methods: Cancer and Aging Resilience Evaluation (CARE) is a prospective registry of older adults (≥60y) with cancer seen at UAB (J Geri Onc 2019; PMID 31005648). Patients with GI malignancies with GA completed within the timeframe of 3 mo. before and up to 6 mo. after diagnosis were included. Vital status (up to 12/7/2019) was ascertained by linking participants to LexisNexis. Multivariable Cox regression analysis was used to estimate associations between GA variables and 1y mortality, adjusting for age at cancer diagnosis, race, cancer stage (IV vs. I-III), cancer group (high risk: pancreatic, hepatobiliary, esophageal vs. low risk: colorectal, GIST, neuroendocrine, etc.), and planned chemotherapy (yes/no). Results: A total of 356 participants met eligibility criteria. Mean age at enrollment was 70y; 56.4% were females; 25% black; 47.1% had high-risk cancers. In unadjusted analysis, high-risk cancers, cancer stage, malnutrition, impaired performance status, limitations in social activities, impaired instrumental activities of daily living (IADL), physical health, mental health, anxiety, and ≥3 comorbidities were associated with higher 1y mortality. Our base model (demographic and clinical variables) demonstrated good discrimination (c statistic 0.758), but was improved with the addition of all significant GA variables (c-statistic 0.810). Fatigue and malnutrition were identified as the strongest predictors among the GA variables, and a model adding those to the base model retained high discrimination (c-statistic 0.804). The estimated 1yr survival was 53.1% for those with both fatigue and malnutrition compared to 88.1% in those with neither. Conclusions: Among older adults with GI malignancies, malnutrition and fatigue were the strongest GA predictors of 1yr mortality after adjusting for age and clinical factors. These findings provide evidence for developing targeted interventions in older patients with newly-diagnosed GI malignancies to reduce 1y mortality.
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Authors: Amod Sarnaik, Nikhil I. Khushalani, Jason Alan Chesney, Karl D. Lewis, Theresa Michelle Medina, Harriet M. Kluger, Sajeve Samuel Thomas, Evidio Domingo Musibay, Anna C. Pavlick, Eric D. Whitman, Salvador Martin-Algarra, Philippa Gail Corrie, Jose Lutzky, Omid Hamid, Renee Wu, Wen Shi, Maria Fardis, Jeffrey S. Weber, James M. G. Larkin, John M. Kirkwood
Journal: Journal of Clinical Oncology (2020)

10006 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) leverages and enhances the body’s natural defense against cancer and has shown durable responses in heavily pretreated melanoma patients. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of efficacy &amp; safety of lifileucel in patients with unresectable metastatic melanoma who have progressed on checkpoint inhibitors and BRAF/MEK inhibitors, if BRAF v600 mutant. We report on Cohort 2 (N = 66) patients who have received TIL. Tumors were resected at local institutions, processed in central GMP facilities for TIL production, manufactured, cryopreserved &amp; shipped back to sites in a 22-day process. Therapy consisted of one week of lymphodepletion, a single lifileucel infusion, and up to 6 IL-2 doses. ORR was based on RECIST v1.1 by investigator assessment. Data cutoff was Feb 2, 2020. Results: Baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), high baseline tumor burden (106 mm mean target lesion sum of diameters), 44% liver/brain lesions, 40.9% LDH &gt; ULN. ORR by investigator was 36.4% (2 CR, 22 PR) and DCR was 80.3%. Mean time to response was 1.9 months (range: 1.3-5.6). After a median study follow-up of 17.0 months, median DOR (mDOR) was still not reached. Six responders have progressed, 2 have died and 2 started other anti-cancer therapy without progression. The adverse event profile was consistent with the underlying advanced disease and the lymphodepletion and IL-2 regimens. Additional follow-up data will be available for presentation. Conclusions: Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAF v600 mutant. Clinical trial information: NCT02360579.
Treatment and prevention of male climacteric syndrome
Authors: Hongjun Li
Journal: BMJ (2017)

男性更年期综合征是一种身心疾病，可治、可防，全面展开以睾酮补充治疗为基础的综合治疗和健康普查为基础的有效预防，有助于提高更年期男性的生命质量，应该引起广泛关注。本文主要介绍睾酮补充治疗的前提、目的、适应证、禁忌证、常用制剂、起效时间、疗程、最佳药物剂量、睾酮补充治疗的益处和安全性评估，同时对其他激素和综合治疗方法进行了适当介绍。
A single institution retrospective study of the effect of starting doses in patients with ER-positive metastatic breast cancer on CDK 4/6 inhibitors.
Authors: Wingsze Liu, Coral Olazagasti, Chung-Shien Lee, Taylor Decina, Karalyn Pappas, Kit Cheng
Journal: Journal of Clinical Oncology (2020)

e13056 Background: CDK4/6 inhibitors (CDKi) have become part of standard of care in the treatment ER-positive, Her2Neu negative of metastatic breast cancer (MBC). Hematologic toxicity from CDKi are common which can lead to dose interruption or dose reduction. There is limited data to compare those who started on full dose and those who started on a reduced dose CDKi. We sought to investigate the impact of reduced starting dose of CDKis. Methods: We conducted a single institution retrospective study on patients (pts) who were treated with CDKi from 2015 to 2019. In this subgroup analysis, we sought to determine the percentage of pts that started on reduced dose CDKi. Pts who were started on reduced dose were compared to those started on standard FDA dose CDKi. Rates of hematologic toxicities, dose interruptions, further dose reductions, progression-free survival and overall survival were compared between the two groups. Data from absolute neutrophil count, hemoglobin and platelet count on Days 1 and 15 of the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Results: Out of 220 pts, 175 (79.6%) pts started on standard starting dose CDKi and 45 (20.5%) pts started on reduced dose CDKi. 30.86% of pts on the standard dosing group and 28.9% of pts on the reduced starting dose group had a dose interruption. The association between starting dose and dose interruption is not statistically significant (p &lt; 0.86). The estimated 12-month survival rate is 95% (95% CI: 89% - 97%) for the pts on standard dose CDKi and 85% (95% CI: 67% - 93%) for the group reduced dose group. The estimated 12-month progression-free survival rate is 72% (95% CI: 64% - 78%) for the standard dosing group and 35% (95% CI: 21% - 50%) for the reduced dose group. Conclusions: Our study showed a significant survival rate and progression-free survival rate difference between patients who were started on standard FDA starting dose compared to those started on reduced dose CDKi.
Successful transition from bortezomib subcutaneous to generic intravenous bortezomib: Cost savings initiative with global economic impact.
Authors: Bhavesh Shah, Radhika Jhaveri, Vaishali Sanchorawala, Adam Lerner, John Mark Sloan, Shayna Sarosiek
Journal: Journal of Clinical Oncology (2020)

e19375 Background: It is estimated that the U.S. will spend $370 billion in 2019 on pharmaceuticals and by 2020 the cost of cancer care will be approximately 158 billion. Cost containment strategies for high cost drugs are needed. There exists an opportunity to decrease overall cost related to bortezomib by switching patients to generic bortezomib. Generic bortezomib was first approved by the FDA in January 2018 but it can only be administered intravenously. Based on previous studies on occurrence of peripheral neuropathy we hypothesized that patients who have not developed bortezomib induced peripheral neuropathy (BIPN) after or during 4 cycles of subcutaneous (subQ) bortezomib could be switched to IV bortezomib without greatly increasing neuropathy. Methods: A protocol was implemented to switch patients from SubQ to IV bortezomib at our hematology outpatient clinic. Patients had to complete 4 cycles of SubQ bortezomib and have either Grade 1 or no BIPN to qualify to switch to IV bortezomib generic formulation. After approval from the hematology/oncology providers and nursing department, this protocol was implemented to start accrual in November 2018. After provider approval for eligible patients, pharmacists would update the treatment plan orders and also notify nursing and patients of the change. Results: Fifteen patients have received at least 1 cycle of IV generic bortezomib for various indications from Nov 2018 to Nov 2019, ranging from 1 cycle to 12 cycles. The diseases for which bortezomib was being used included multiple myeloma (n = 8) and AL amyloidosis (n = 2), renal transplant rejection and thrombotic thrombocytopenic purpura (TTP). Two of the 15 patients had Grade 1 BIPN prior to switching, while all others reported no neuropathy prior to the switch. None of the patients have developed new neuropathy after making the switch from subQ to IV bortezomib. Nursing and patient satisfaction surveys showed that majority of both groups did not have a preference for IV versus subQ administration. Conclusions: We describe a method to switch from subcutaneous bortezomib to generic IV bortezomib instituted at a large academic medical center as a cost containment strategy. This has resulted in no new cases of neuropathy in our growing data set.
Accounting for cell type hierarchy in evaluating single cell RNA-seq clustering
Authors: Zhijin Wu, Hao Wu
Journal: Genome biology (2020)

Abstract Cell clustering is one of the most common routines in single cell RNA-seq data analyses, for which a number of specialized methods are available. The evaluation of these methods ignores an important biological characteristic that the structure for a population of cells is hierarchical, which could result in misleading evaluation results. In this work, we develop two new metrics that take into account the hierarchical structure of cell types. We illustrate the application of the new metrics in constructed examples as well as several real single cell datasets and show that they provide more biologically plausible results.
Economic assessment of diagnostic revision in peripheral T-cell lymphoma.
Authors: Julie M. Lisano, Nicholas Liu, Kristina Yu-Isenberg, Deepak Singh, David Campbell, Wayne Su
Journal: Journal of Clinical Oncology (2020)

e20039 Background: Peripheral T-cell lymphoma (PTCL) is a rare disease that is challenging to diagnose. A retrospective claims analysis and parallel electronic health records analysis estimated the rate of PTCL diagnostic revision (DR) either to or from other lymphomas at 29.3%, with significantly higher costs for DR than non-DR patients during follow-up. The current study used data from this analysis to estimate the cost of DR in PTCL to US health plans and quantify the potential impact of reducing DR in this population. Methods: A cost calculator was developed using pharmacy and medical costs for adult patients in the IBM MarketScan Commercial and Medicare Supplemental Databases with a PTCL diagnosis from 01/10-06/17, with or without DR (≥1 medical claim for a non-PTCL lymphoma in the year prior to or after the index PTCL diagnosis). Cost data were incorporated for non-DR, DR to PTCL, and DR from PTCL cohorts, and for the DR period (time from initial PTCL diagnosis to non-PTCL diagnosis or vice versa) and subsequent follow-up period. In the current scenario (based on the analysis of MarketScan data), rates of DR were 29.3%, of which 51.4% were DR to PTCL and 48.6% from PTCL. DR periods were 5.0 and 3.7 months, respectively, over a 1-year time horizon. A ‘new’ scenario was included that assumed a 50% reduction in the rate of DR to and from PTCL, and a 50% reduction in the length of DR period. Results: Total per patient per month (PPPM) costs for adults in a Medicare health plan diagnosed correctly or incorrectly with PTCL were estimated at $13,064 in the current scenario and $12,131 in the new scenario, representing a savings of $933 PPPM assuming a 50% reduction in both the rate of DR and the DR period. Savings were largely derived from reduced costs associated with other outpatient services ($385 PPPM) and inpatient services ($367 PPPM) in the new scenario (Table). In a hypothetical 1 million member Medicare plan, the estimated total plan savings annually in the new scenario would be $906,801, based on an estimated 81 PTCL patients among all plan members. Conclusions: Accurate and timely diagnosis of PTCL is essential to enable appropriate treatment. Interventions that reduce the rate of DR in PTCL are likely to result in potential cost-savings to US health plans. [Table: see text]
Changes of serum leptin levels in patients with premature ejaculation after sertraline treatment
Authors: Kun-long Tang, Bao-long Wang, Li-ming Li, Yong Zhou, Chang-hai Yang
Journal: BMJ (2012)

Fifty nine patients with premature ejaculation (PE) received sertraline treatment for 8 weeks.The average intravaginal ejaculation latency time (IELT) and the scores of Chinese index of premature ejaculation (CIPE) were evaluated and the fasting serum leptin levels were measured before and after treatment,all the values were compared with those of 64 normal male controls.The serum leptin levels were higher,the IELT and CIPE scores were lower in PE patients than those in normal controls before treatment.After 8 weeks of treatment with sertraline,the levels of serum leptin in PE patients decreased to normal levels,CIPE and IELT increased.The results indicate that serum leptin can be used as a bioindicator for diagnosis of premature ejaculation and assessment of therapeutic efficacy in PE patients.

Key words: 
Premature ejaculation; Leptin
Novel blood-based biomarker predicting severe toxicity in melanoma anti-CTLA-4 immunotherapy treatment.
Authors: Vylyny Chat, Robert Ferguson, Leah Morales, Kelsey Monson, Eduardo Esteva, Una Moran, Anna C. Pavlick, Paolo Antonio Ascierto, Iman Osman, Jeffrey S. Weber, Tomas Kirchhoff
Journal: Journal of Clinical Oncology (2020)

3077 Background: Immune checkpoint inhibition (ICI) has improved clinical outcomes of metastatic melanoma (MM). However, 65-80% of treated patients experience immune-related adverse events (irAEs), urging for the availability of personalized and easy-access clinical biomarkers. We have previously shown that germline genetics related to host immunity affects ICI response and MM survival. In this study, we investigated if germline immune-related expression quantitative trait loci (ieQTLs) may predict ICI-induced irAEs in MM. Methods: Through a comprehensive interrogation of a healthy twin-cohort expression dataset (MuTHER), we identified 40 ieQTLs most significantly associated with the expression of 382 immune-related genes. These germline variants were genotyped using the MassARRAY system in anti-CTLA-4-treated MM patients, collected as part of a multi-institutional collaboration. Using multivariable logistic regression models, we tested the association of 40 ieQTLs with irAEs in a discovery cohort of 97 MM patients followed by a validation in additional cohort of 97 anti-CTLA-4 treated patients. Results: We found rs7036417 significantly associated with severe anti-CTLA-4 irAEs in the discovery (OR = 6.18; 95%CI = 1.61-23.74; p = 0.007) and validation (OR = 6.73, 95%CI = 1.42-31.86; p = 0.02) cohorts. Pooled analysis showed that carriers of two rs7036417 alternate alleles (TT) have a 6-fold increased risk of developing severe irAEs (OR = 6.11; 95% = 2.26-16.56;p = 0.0003). This association was not observed with ICI response or survival. The alternate allele of rs7036417 is associated with higher expression of SYK (spleen-associated tyrosine kinase), suggesting that elevated SYK contributes to developing severe irAEs. Conclusions: We report that rs7036417, an ieQTL in SYK, associates with an increased risk of severe irAEs, independent of ICI efficacy. SYK plays an important role in B-cell/T-cell expansion and increased pSYK has been reported in patients with rheumatoid arthritis or systemic lupus erythematosus. Based on our data, the over-expression of SYK likely explains the biological mechanisms of the association between rs7036417 and anti-CTLA4 irAEs. These findings propose a novel blood-based baseline biomarker stratifying the patients at increased risk of severe irAEs, with a clinical effect substantially surpassing those observed for currently available predictors. Our ongoing studies are currently investigating SYK eQTL as a novel target in toxicity-reducing therapies.