tbuckley/cabot-search huggingface dataset:
Use of real-world clinical lab data to reveal Asian NTRK fusion test availability patterns.
Authors: Markus Eckstein, Kenneth Joel Bloom, Susanne Munksted Fosvig, Marieke Hoefsmit, Jordan Clark
Journal: Journal of Clinical Oncology (2020)

e15574 Background: The development and launch of first-generation tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib and entrectinib, has brought targeted treatment options to neurotrophic tropomyosin-related kinase (NTRK) fusion–positive adult and pediatric cancer patients who may have been out of treatment options. Widespread adoption of NTRK fusion testing is needed to support successful selection of patients for these TRK inhibitors as well as other targeted therapies. The objective of this study was to investigate global availability of NTRK fusion testing, with a specific focus on Asia. Methods: For this study, real-world clinical pathology laboratory data, derived from Diaceutics’ proprietary Global Diagnostic Index (GDI) of more than 2500 labs, were investigated to assess the current footprint of NTRK fusion testing in Asia. Availability of clinical routine testing was analyzed in selected cohorts of laboratories across different regions, comparing Asia to the US and Europe. Laboratories were included based on their large volume of testing or on their importance (e.g., large academic and large commercial laboratories). Results: Data on availability of NTRK fusion testing by clinical laboratories reveal different patterns of NTRK fusion test adoption in Asia, depending on the region under study. In China and similarly in the US, Italy, and France clinical NTRK fusion testing is already being performed by the majority of laboratories from the selected cohort. In Japan, physicians have limited access to testing, with only a few laboratories from the selected cohort performing testing for NTRK fusions. Conclusions: NTRK fusion testing is essential for identifying patients eligible for first-generation TRK-inhibitors. Various laboratories across selected cohorts of labs in China and Japan lack the capability to initiate clinical NTRK fusion testing in-house, denying some patients the potential benefit from these breakthrough therapies. Consequently, patient outcomes will be suboptimal due to lack of testing infrastructure. The readiness of Asian markets to support patient selection successfully can affect the rate of testing and the impact of these innovative therapies on patients’ lives. [Table: see text]
Deviation from the precisely timed phenomic ageotypes can assist in early CRC screening and reveal underlying pathophysiology.
Authors: Sheeno P. Thyparambil, Jin You, Kang Liu, Hui Sun, Junjie Peng, Sanjun Cai, Yaqi Li, Chen Fu, Pingping Bao, Qing Li, Shiying Hao, Yani Zhang, Zhen Li, Jingzhi Yang, Ziyu Yin, Xiaoming Yao, Xiurui Zhu, James Schilling, Karl G. Sylvester, Xuefeng B. Ling
Journal: Journal of Clinical Oncology (2020)

e16098 Background: Human serum proteome and metabolome profiles have been analyzed to explore the molecular changes that occur with aging. We hypothesized that deep phenomic profiling of longitudinal sera would allow the identification of distinct phenomic chronologic patterns as a normal biological clock baseline to study personal aging. We further hypothesized that molecular assessment of this chronologic deviation, due to advance adenoma and early CRC, from the normal reference ageotypes would be instrumental as potential early diagnostics and reveal underlying pathophysiology. Methods: A cohort of 7673 normal, 746 advanced adenoma, 1177 stage I, 103 stage II and 119 stage III blood samples were assembled. Innovative multi-omics approaches, with global and targeted LCMS data production (metabolomics, lipidomics, and 2D proteomics), were applied to deep profile these subjects. Identification of the age-associated molecular patterns in normal subjects, modeled with an elastic net algorithm, established the reference baseline to mirror a biological clock. CRC associated deviation from this chronologically paced multi-omics clock was quantified to screen for early CRCs and explore the underlying pathophysiology. Results: Multiple mProbe aging indices of proteins and metabolites were identified, strongly predicting chronologic age ( P &lt; 0.001, R &gt; 0.90). Significant disruptions from normal molecular patterns were observed in advanced adenoma and early CRCs patients (R &lt; 0.7). Pathway analysis of the proteins/metabolites with deviating patterns revealed both known and new pathways underlying CRC. Unsupervised cluster analysis identified unique aging subgroups among advanced adenoma and different stage CRC patients, indicating unique underlying biology relating to aging with different severities of cancer burdens. Conclusions: Deviations from the meticulously timed phenomic aging patterns may provide utility to allow future early CRC screening. Close examination of the underlying pathophysiology associated with early CRC, relating to ageotypes, not only may improve the sensitivity and specificity of prognostic and diagnostic tests of early CRCs, but also shed new insights into CRC therapeutics.
A phase III, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).
Authors: Danny Rischin, Matthew G. Fury, Israel Lowy, Elizabeth Stankevich, Hyunsil Han, Sandro Porceddu
Journal: Journal of Clinical Oncology (2020)

TPS10084 Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is &gt; 95%, a proportion of pts are considered to have high risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti‒PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Methods: This randomized, placebo-controlled, double-blind, multicenter, Phase 3 study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT (NCT03969004). Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion, and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomized 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. This study is currently open for enrollment. Clinical trial information: NCT03969004.
Comparison of intranasal dexmedetomidine and oral chloral hydrate administration for deep sedation in children: a meta-analysis
Authors: Tianliang Hou, Long Yang, Yewei Zhu, Yanhua Wang
Journal: BMJ (2020)

Objective
To compare the effect of intranasal dexmedetomidine and oral chloral hydrate in deep sedation of children.


Methods
The Pubmed, EMBase, CENTRAL (Issue 4, 2018), Web of science, CBM, Wanfang Data, CNKI and VIP databases from the inception to January 2019 were searched. Randomized controlled trials (RCTs) with dexmedetomidine and chloral hydrate as interventions were included and the data were analyzed by RevMam 5.3 and Stata 12.0 software. The success rate of deep sedation, the indicator of sedation onset time, the recovery time, the incidence of vomiting and bradycardia were compared.


Results
A total of 7 RCTs involving 1 007 patients were included for analysis. The results showed that the success rate of deep sedation (OR=2.55, 95%CI:1.46-4.44, P<0.01) and the incidence of bradycardia (OR=4.42, 95%CI:1.82-10.74, P<0.01) in the dexmedetomidine nasal group were significantly higher than those in the chloral hydrate oral group. The recovery time was significantly shorter (MD=-16.41, 95%CI:-21.54-11.28, P<0.01) and the incidence rate of vomiting (OR=0.04, 95%CI:0.01-0.17, P<0.01) in dexmedetomidine nasal group was significantly lower than those in the chloral hydrate oral group. There was no significant difference in the indicator of sedation onset time (MD=-0.47, 95%CI:-2.71-1.22, P=0.46).


Conclusion
Compared with the traditional oral chloral hydrate, intranasal dexmedetomidine has a higher sedation success rate and shorter recovery time after sedation with a lower incidence of nausea and vomiting.


Key words: 
Chloral hydrate; Dexmedetomidine; Meta-analysis; Children, medium and deep sedation; Randomized controlled trial
Induction and maintenance for chronic myeloid leukemia-chronic phase: A novel treatment strategy.
Authors: Aditi Jain, Manoranjan Mahapatra, Tulika Seth, Anil Irom, Sudha Sazawal
Journal: Journal of Clinical Oncology (2020)

e19526 Background: Imatinib remains the standard of care for CML-CP in many countries because of its affordability and safety with long term use. Given that upfront Nilotinib has higher rates of major molecular response and early deep responses predict long term responses, we hypothesized that upfront Nilotinib as induction followed by Imatinib maintenance may help to capitalize on the efficacy of Nilotinib without sacrificing the safety and efficacy of Imatinib. Methods: CML CP patients were divided into 3 groups at the time of diagnosis. Group 1 received Imatinib 400mg OD upfront, Group 2 and 3 received Nilotinib 300 mg BD for 1st 3 and 6 months respectively then switched over to Imatinib 400 OD. Quantitative real time PCR for BCR-ABL (RQ PCR for BCR-ABL) was done at 3, 6,12, 18, 24, 30, and 36 months to assess response. 3 early molecular responses were defined for analysis. EMR 1 was defined as Bcr-abl RQPCR &lt; 10% at 3 months, EMR 2 as &lt; 1% at 6 months and EMR 3 as &lt; 0.1% at 6 months. Results: Patients on Nilotinib induction had deeper responses than patients on Imatinib at 3 and 6 months. However, subsequent molecular responses were similar in all 3 groups. The rates of Early Molecular responses were significantly better in the Nilotinib group compared to the Imatinib group. Significantly lesser patients in Group 1 had EMR 1 compared to Groups 2 and 3 [80.49% vs 100% vs 95.56%, p value 0.001]. Results were similar for EMR 2 and 3 [EMR 2: 34.15% vs 42.11% vs 60%, p value 0.017, EMR 3: 25.71% vs 25.53% vs 44.44%, p value Group 1 vs Group 3: 0.030]. TKI failure/progression rates were significantly better amongst patients who achieved EMR vs those who did not achieve EMR for EMR 2 and 3 but not EMR 1. For EMR 2, 42.68% who did not achieve EMR eventually had TKI failure compared to 18.03% of those who achieved EMR (p value 0.002). Similarly, 32.95% who failed to achieve EMR 3 progressed vs 11.9% of those who achieved EMR 3 (p value 0.011). 3 patients in group 1 and 1 patient in group 2 developed T315I mutation while none did in Group 3. Conclusions: The early advantage achieved with Nilotinib Induction was not sustained after switching to Imatinib maintenance. Nevertheless, target responses were still achieved and similar failure rates were present in all 3 groups. Patients who attained an EMR &lt; 1 % at 3 months or &lt; 0.1% at 6 months tend to have higher EFS and lower rates of TKI failure/progression irrespective of the treatment arm.
Hemoglobin levels of pregnant women on the first outpatient visit
Authors: Yue Teng, Qin-bing Yang
Journal: BMJ (2010)

Five hundred and seventy four pregnant women in the 10th to 14th gestational weeks were accidentally sampled, their hemoglobin levels were measured, and related factors were investigated and analyzed. The average hemoglobin level of all the sampled pregnant women was 123. 8 g/L, while 27 were under 110 g/L accounting for 4. 7 %. The hemoglobin levels were positively correlated with body mass index (BM1) before pregnancy, frequency intake of animal liver and blood products and number of pregnancy;while were negatively correlated with gestational weeks. The results suggest that anemia prevention should focus on women whose BMI is lower than the average before pregnancy, start from the 13th gestational week,and more food rich in iron should be taken to improve the hemoglobin levels. Meanwhile, it is also important to reduce the number of pregnancy.

Key words: 
Pregnancy;  Hemoglobin
A qualitative study of a blended therapy using problem solving therapy with a customised smartphone app in men who present to hospital with intentional self-harm
Authors: Mackie Craig, Dunn Nicole, MacLean Sarah, Testa Valerie, Heisel Marnin, Hatcher Simon, 孟雪
Journal: BMJ (2018)

前言
混合疗法描述了使用计算机化治疗与面对面治疗相结合的方法，以扩展面对面治疗的深度、范围和性质。我们想要开发一种治疗手册，在因自残入院的男性患者身上进行结合面对面的问题解决和一款智能手机应用程序（APP）的混合治疗随机试验。


对象
开发一种治疗手册，并描述接受和提供混合治疗的经验。


方法
在完成混合治疗后，与参与者进行了半结构式的定性访谈，以描述他们的治疗经验。两个独立的编码人员使用一种主题的、基于理论的方法分析了这些材料。


发现
7名男性参加了本研究，其中6人完成了定性访谈。确定的两个主要主题是信任和联系。参与者参加了85%的预约。


结论
在治疗手册中，我们通过在面对面访谈部分中允许时间讨论APP，从而强调了信任和联系的主题，以确保治疗师熟悉这款APP，并知道如何应对技术问题。对信任和联系的认同提出了新的问题，即与其强调治疗与技术相结合，不如关注人的重要性。


临床意义
临床医生和APP开发人员需要关注技术与治疗的关系，因为信任和良好的沟通很容易被破坏，从而导致患者不再应用APP。混合疗法可能会增加面对面治疗的持久性。


注册号码
NCT02718248。
The landscape of predictive biomarkers for ATR inhibition in Chinese solid-tumor patients.
Authors: Rong Shen, Qiuan Yang, Zimin Liu, Yongjie Wang, Xinglong Fan, Lei Li, Bo Hu, Wenjing Xiao, Meili Ma, Wei Chen, Xiaoyan Liu, Weiwei Shi, Angen Liu
Journal: Journal of Clinical Oncology (2020)

3626 Background: Ataxia Telangiectasia and Rad3-related (ATR) is one of the core regulators participating in DNA damage response as a sensor of replication stress. Besides, ATR also plays a role in cell cycle checkpoint activation and DNA replication regulation. Several ATR inhibitors (ATRi) have been demonstrated in anti-cancer clinical trials. Herein, we describe the distribution of selected biomarkers, which have been shown to predict a higher sensitivity to ATRi according to preclinical data, in Chinese cancer population. Methods: FFPE tumor tissues and matched blood samples from 10,194 Chinese patients with 25 different types of solid tumors were collected. NGS based 450 cancer genes panel assay were performed to detect genomic alterations, including SNV, short and long insertions/deletions, CNV and rearrangements/fusions. The testing was carried out by a CAP accredited and CLIA certified laboratory. Results: The prevalence of ARID1A mutations, ATM mutations, BRCA1/BRCA2 mutations, MYC amplification, and CCNE1 amplification accounted for 9.5%, 4.7%, 6.0%, 3.5% and 3.3% of this cohort respectively. The most common tumors with ARID1A mutations were endometrial carcinoma (EC, 34.4%), gastric carcinoma (GC, 19.4%), small bowel carcinoma (SBC, 19.3%), intrahepatic cholangiocarcinoma (19.3%), extrahepatic cholangiocarcinoma (17.7%) and urothelial carcinoma (UC, 16.7%). For ATM mutations, the prevalence was colorectal carcinoma (CRC, 8.9%), SBC (8.8%), pancreatic cancer (7.8%), UC (7.3%), gallbladder carcinoma (GBC, 7.1%) and GC (6.8%). For BRCA1/BRCA2 mutations, the prevalence was ovarian carcinoma (29.5%, Germline 23%), breast carcinoma (13.3%, Germline 7.1%), EC (11.5%, Germline 3.3%), UC (10.4%), melanoma (8.5%) and CRC (7.9%). For MYC amplification, the prevalence was breast carcinoma (10.2%), ovarian carcinoma (9.2%), esophageal carcinoma (7.2%), thymic tumor (6.1%), cancer of unknown primary (CUP, 5.8%) and gastrointestinal neuroendocrine tumor (GI-NET, 5.4%). For CCNE1 amplification, the prevalence was GC (11.9%), GBC (8.8%), bone sarcoma (7.7%), ovarian carcinoma (6.9%), CUP (4.2%) and GI-NET (4.1%). Conclusions: Our study reported the prevalence of gene mutations of ATRi sensitivity determinants in a large cohort of Chinese cancer patients. The results revealed the high prevalence and different distribution of these biomarkers across a wide spectrum of cancers. The genomic profile study also provided information for ATRi sensitivity assessment and the drug combinations with ATR inhibition.
The quantitation of thioredoxin 1 from serum as a novel means to detect breast cancer (BC).
Authors: Kyoung Hoon Suh
Journal: Journal of Clinical Oncology (2020)

557 Background: Breast cancer (BC) is the most common cancer and the second leading cause of cancer death in women. Enormous effort has been conducted without success to develop a means to detect BC using the blood. We have reported that the level of thioredoxin 1 (Trx1) in serum could be a novel standard to evaluate the risk of BC. Therefore, we have investigated the clinical utility of Trx1 as a biomarker to detect BC by testing sera from normal women, women with BC, women with five other types of cancer. Methods: We have developed an ELISA kit that quantitates Trx1 in sera. The level of Trx1 was determined in each serum from normal healthy women (n = 114), as well as patients with BC (n = 106), cervical cancer (n = 17), lung cancer (n = 14), stomach cancer (n = 9), and thyroid cancer (n = 4). BC patients were recruited according to their age and cancer stage. Each test was duplicated more than three times, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests. Results: The mean value of Trx1 from normal women was 5.60±4.39(±SD) and that from BC was 22.25±7.07. The Trx1 level was effective to distinguish BC serum from healthy serum with a sensitivity of 94.3% and specificity of 93.9% (AUC 0.985, p&lt; 0.001). The levels of Trx1 from BC patients were higher than the cut-off value of 14.13 U/ml regardless of age, stage, histological grade, type, ER/PR/HER2 expression profile, and proliferation activity of BC cells. The levels of Trx1 from the other five types of cancers (2.34±1.82 - 3.64±2.99) were low enough to be distinguishable from BC. Especially, Trx1 levels could rescue patients whose mammography resulted in a false judgement. Conclusions: These results indicated that the blood level of Trx1 is an effective and accurate method to detect breast cancer, and particularly as a complement to mammography.
只是支气管哮喘吗
Authors: 习森, 贾永华
Journal: BMJ (2009)

有一个女患者,81岁,第1次来我们社区卫生服务中心就诊.主诉咳嗽、喘憋、呼吸困难伴咳痰2天.患者2天前因闻油漆气味后出现上述症状,自服氨茶碱、抗炎药,吸氧后可基本缓解.今晨受凉后再次加重,服氨茶碱并吸氧未见好转,咳嗽伴大量白痰,无咳粉红色泡沫样痰,夜间不能平卧,喘憋加重时患者坐位呼吸.无发热、头痛,无心慌心悸,无胸骨后压榨性疼痛,无恶心呕吐,无腹痛腹泻,食欲差,二便正常.患者自20岁开始每年均有类似发作,都在三级医院呼吸科就诊,每次经抗炎、平喘、止咳治疗后好转。
The utility of routine endocrinopathy testing in patients treated with ipilimumab for solid malignancies.
Authors: Grant Jester, Talat Almukhtar, Jennifer Tseng
Journal: Journal of Clinical Oncology (2020)

e19250 Background: It is recommended to periodically screen for endocrine immune-related adverse events during the administration of ipilimumab(ipi) and nivolumab(nivo) immunotherapy. ACTH and TSH levels are used to screen for possible autoimmune dysfunction of the pituitary and thyroid glands. Patients treated with immunotherapy at our institution undergo pre-set laboratory testing of ACTH and TSH levels prior to initial administration, and then a minimum of every 6-8 weeks depending on the treatment interval and physician preference. We aimed to evaluate the impact of routine endocrinopathy testing on clinical management and the overall utility of this testing. Methods: This is a retrospective chart review of patients treated at the UF Health Cancer Center Orlando with ipilimumab and the combination of Ipi/Nivo immune checkpoint inhibitors for solid malignancies over a 28-month period. We collected ACTH, TSH, Cortisol, and T4 laboratory data during the first 100 days of treatment and analyzed the electronic medical record for endocrinopathy diagnoses, influencing factors for ACTH results, and changes in clinical management as a result of routine ACTH screening. Results: In total, 7 patients were treated with ipilumumab single agent, and 35 patients were treated with Ipi/Nivo combination. An Immune related endocrinopathy was diagnosed in 6(14%) patients. 20 (48%) patients had at least one abnormally low ACTH value during the first 100 days of treatment. 75% of patients with abnormally low values had an ACTH level checked while on steroids. 62% of abnormally low ACTH tests did not have an accompanying cortisol level ordered. 57% of patients had ACTH testing performed in both the morning and afternoon. None of the patients with abnormally low ACTH levels had documentation which supported that ACTH/TSH testing led to brain imaging or additional pituitary hormone testing. None of the patients had their immunotherapy medication delayed or stopped as a result of routine ACTH testing. Conclusions: ACTH testing in patients treated with immunotherapy is frequently abnormal and can be exceedingly difficult to interpret. ACTH testing at our institution was often performed in the setting of multiple changing variables and abnormal values were frequently not investigated further. Routine ACTH testing did not impact clinical management.
双环压榨包皮环切术157例分析
Authors: 自胜氢, 李维艳
Journal: BMJ (2008)

为避免包皮环切术包皮系带损伤,减少术后血肿、术后感染等并发症,以及包皮环切术后敷料固定及更换不便的不足,本研究于2004年6月至2007年10月自制压榨环,应用双环压榨法对包皮环切手术进行改良.经157例对比观察,效果满意.